Biomarker Insights[JOURNAL]
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200 papers
Decreased Serum Insulin Receptor Messenger RNA Level in IgG Seropositive Type 2 Diabetic Patients.
Tagoe EA, Appiah JA, Boateng PA … +2 more , Quaye O, Bosomprah S
Biomark Insights · 2024 · PMID 39502307 · Full text
BACKGROUND: Helicobacter pylori (H. pylori) is a known gastro-intestinal pathogen but implicated in extra-gastric diseases. The relationship between H. pylori infection and type 2 diabetes (T2DM) remains insufficiently e...
BACKGROUND: Helicobacter pylori (H. pylori) is a known gastro-intestinal pathogen but implicated in extra-gastric diseases. The relationship between H. pylori infection and type 2 diabetes (T2DM) remains insufficiently elucidated, particularly in terms of molecular mediators such as microRNAs (miRNAs) and messenger RNAs (mRNAs). OBJECTIVE: We aimed to characterize expression pattern of insulin signalling mRNAs and targeted miRNAs in T2DM patients exposed to H. pylori infection. METHODS: We conducted a cross-sectional study among patients diagnosed with type 2 diabetes mellitus and were aged 18 to 60 years. Overnight fasting blood samples were collected and processed for plasma and serum. The plasma samples were used for glucose estimation and the serum used for H. pylori IgG screening. Total RNA was extracted from the serum with commercial kit, and mRNAs and miRNAs quantified by RT-qPCR with specific primers and under predetermined amplification conditions. Clinical data were obtained from medical records of patients. RESULTS: Among 351 patients enrolled, 267 (76.1%) were females, 224 (63.8%) were married, and 79 (22.5%) had tertiary education. Expression level of insulin receptor mRNA was significantly lower in H. pylori positive T2DM patients compared to H. pylori negative ( < .05). There was no evidence of a difference in insulin receptor substrate 1 mRNA level ( > .05). Although not statistically significant, the expression levels of miRNA-222 and miRNA-155 in the patients exposed to were higher than that of the unexposed group ( > .05). CONCLUSIONS: We found a significantly reduced serum insulin receptor messenger RNA level and higher levels of miRNA-222 and miRNA-155 in H. pylori exposed T2DM patients. The findings suggest a possible role of the infection in insulin signalling alteration in the patients.
Systematic Analysis and Insights Into the Mutation Spectrum and Ethnic Differences in ATP7B Mutations Associated With Wilson Disease.
Lao TD, Le TAH
Biomark Insights · 2024 · PMID 39502306 · Full text
BACKGROUND: (ATPase copper transporting beta gene) is constituted of 21 exons, and codes for a 1465 amino acid. The protein of ATP7B plays an key role of copper metabolism. Many previous reports indicated that mutations...
BACKGROUND: (ATPase copper transporting beta gene) is constituted of 21 exons, and codes for a 1465 amino acid. The protein of ATP7B plays an key role of copper metabolism. Many previous reports indicated that mutations in are well known to cause defective copper transporting copper-transporting ATPase 2 protein leading to the accumulation of copper, resulting the Wilson disease. OBJECTIVES: The meta-analysis was performed to comprehensive gain a thorough grasp of the spectrum of genetic variations. DESIGN: A meta-analysis was conducted according to the guiding of PRISMA. aiming to assess the diversity and frequency of mutations in the gene, with an emphasis on mutations located within specific exons. DATA SOURCES AND METHODS: The dataset of detected mutations within their positions, types as well as nomenclature, were recorded from previous studies (spanning the year from 2013 to 2023). The analysis focused on exon-specific variations and their prevalence across different populations. RESULTS: A total of 40 studies were enrolled into current data analysis. Our comprehensive study revealed a variety of mutations, most notably over 50% of single nucleotide changes described, distributed over the 21 exons of the gene. Focusing on the exon 8, itisplayed the most diversity of mutations, with 18 studies identifying 53 unique variants, the majority of which were missense mutations (81.13%). Additionally, the variations c.2333G>A/T (p.R778Q/L), c.2305A>G (p.M769V), c.2336G>A (p.W779*), and c.2304dupC (p.M769HfsX26) are reported in many populations. The weighted mean of variants' proportion was used to calculate the pooled estimate of these percentages, which were 14.19% for c.2333G>A/T (p.R778Q/L), 2.70% for c.2305A>G (p.M769V), 1.42% for c.2336G>A (p.W779*), and 2.33% for c.2304dupC (p.M769HfsX26). CONCLUSION: This design demonstrate to identify the spectrum of gene's mutations, especially exon 8, offering important insights into the prevalence and significance of exon 8 mutations. Understanding the mutation in the gene offers insights into the mechanisms behind WD and guides strategies for diagnosis and treatment.
The Chromosome Passenger Complex (CPC) Components and Its Associated Pathways Are Promising Candidates to Differentiate Between Normosensitive and Radiosensitive ATM-Mutated Cells.
Dietz A, Subedi P, Azimzadeh O … +13 more , Duchrow L, Kaestle F, Paetzold J, Katharina Payer S, Hornhardt S, von Toerne C, Hauck SM, Kempkes B, Kuklik-Roos C, Brandes D, Borkhardt A, Moertl S, Gomolka M
Biomark Insights · 2024 · PMID 39493730 · Full text
BACKGROUND: Sensitivity to ionizing radiation differs between individuals, but there is a limited understanding of the biological mechanisms that account for these variations. One example of such mechanisms are the mutat...
BACKGROUND: Sensitivity to ionizing radiation differs between individuals, but there is a limited understanding of the biological mechanisms that account for these variations. One example of such mechanisms are the mutations in the ATM (mutated ataxia telangiectasia) gene, that cause the rare recessively inherited disease Ataxia telangiectasia (AT). Hallmark features include chromosomal instability and increased sensitivity to ionizing radiation (IR). OBJECTIVES: To deepen the molecular understanding of radiosensitivity and to identify potential new markers to predict it, human ATM-mutated and proficient cells were compared on a proteomic level. DESIGN: In this study, we analyzed 3 cell lines from AT patients, with varying radiosensitivity, and 2 cell lines from healthy volunteers, 24 hours and 72 hours post-10 Gy irradiation. METHODS: We used label-free mass spectrometry to identify differences in signaling pathways after irradiation in normal and radiosensitive individuals. Cell viability was initially determined by water soluble tetrazolium (WST) assay and DNA damage response was analyzed with 53BP1 repair foci formation along with KRAB-associated protein 1 (KAP1) phosphorylation. RESULTS: Proteomic analysis identified 4028 proteins, which were used in subsequent in silico pathway enrichment analysis to predict affected biological pathways post-IR. In AT cells, networks were heterogeneous at both time points with no common pathway identified. Mitotic cell cycle progress was the most prominent pathway altered after IR in cells from healthy donors. In particular, components of the chromosome passenger complex (INCENP and CDCA8) were significantly downregulated after 72 hours. This could also be verified at the mRNA level. CONCLUSION: Altogether, the most striking result was that proteins forming the chromosome passenger complex were downregulated after radiation exposure in healthy normosensitive control cells, but not in radiosensitive ATM-deficient cells. Thus, mitosis-associated proteins form an interesting compound to gain insights into the development and prediction of radiosensitivity.
D-dimer as a Predictive Biomarker of Response to Chemotherapy in Patients With Metastatic Breast Cancer.
Alkhoder L, Salamoon M, Saifo M … +1 more , Alwassouf S
Biomark Insights · 2024 · PMID 39429952 · Full text
BACKGROUND: Tumor-induced coagulation is widely observed in cancer patients. Moreover, it is associated with tumorigenesis, tumor progression and metastasis, by creating a proliferative and proangiogenic microenvironment...
BACKGROUND: Tumor-induced coagulation is widely observed in cancer patients. Moreover, it is associated with tumorigenesis, tumor progression and metastasis, by creating a proliferative and proangiogenic microenvironment. Therefore, D-dimer, a fibrin degradation product, correlates with tumor prognosis in several cancer types. OBJECTIVES: This study aims to investigate whether D-dimer levels can be a predictive and monitoring indicator for chemotherapy response in metastatic breast cancer (MBC) patients. DESIGN: This was a prospective study. METHODS: This study included two groups, 76 patients diagnosed with metastatic breast carcinoma and 25 patients with primary breast carcinoma. Plasma D-dimer levels were measured prospectively before chemotherapy initiation, and after the fourth treatment cycle in MBC patients. D-dimer levels before chemotherapy (D0) were analyzed using Receiver Operating Characteristic (ROC) curves to determine the optimal cut-off baseline values of D0, and to evaluate their discriminatory abilities in predicting response to chemotherapy. RESULTS: In the preliminary response evaluation, the mean level of D-dimer significantly decreased by 0.65 μg/ml in patients with partial response patterns, and by 0.5 μg/ml in patients with stable disease. In the disease progression group, a marked increase was seen in D-dimer levels by 1.2 μg/ml. Analysis of ROC curves showed that D-dimer levels at D0 could discriminate the response to chemotherapy, whereas progressive disease rate correlated with higher levels of D-dimer. CONCLUSION: D-dimer level in plasma is a useful predictive and monitoring marker of response to chemotherapy in metastatic breast cancer.
Biomarkers From Discovery to Clinical Application: In Silico Pre-Clinical Validation Approach in the Face of Lung Cancer.
Kori M, Gov E, Arga KY … +1 more , Sinha R
Biomark Insights · 2024 · PMID 39371614 · Full text
BACKGROUND: Clinical biomarkers, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker...
BACKGROUND: Clinical biomarkers, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker identification of putative biomarkers, validation of biomarkers is necessary for translation of discoveries into clinical application. OBJECTIVE: Accordingly, in this study, we emphasize the potential of in silico approaches and have proposed and applied 3 novel sequential in silico pre-clinical validation steps to better identify the biomarkers that are truly desirable for clinical investment. DESIGN: As protein biomarkers are becoming increasingly important in the clinic alongside other molecular biomarkers and lung cancer is the most common cause of cancer-related deaths, we used protein biomarkers for lung cancer as an illustrative example to apply our in silico pre-clinical validation approach. METHODS: We collected the reported protein biomarkers for 3 cases (lung adenocarcinoma-LUAD, squamous cell carcinoma-LUSC, and unspecified lung cancer) and evaluated whether the protein biomarkers have cancer altering properties (i.e., act as tumor suppressors or oncoproteins and represent cancer hallmarks), are expressed in body fluids, and can be targeted by FDA-approved drugs. RESULTS: We collected 3008 protein biomarkers for lung cancer, 1189 for LUAD, and 182 for LUSC. Of these protein biomarkers for lung cancer, LUAD, and LUSC, only 28, 25, and 6 protein biomarkers passed the 3 in silico pre-clinical validation steps examined, and of these, only 5 and 2 biomarkers were specific for lung cancer and LUAD, respectively. CONCLUSION: In this study, we applied our in silico pre-clinical validation approach the protein biomarkers for lung cancer cases. However, this approach can be applied and adapted to all cancer biomarkers. We believe that this approach will greatly facilitate the transition of cancer biomarkers into the clinical phase and offers great potential for future biomarker research.
Exploring the Correlation Between Hypoxia, Variants, and Breast Cancer in Different Ethnicities, and Bangladeshi Women: Through ELISA and Integrative Multi-Omics Analysis.
Islam MS, Jesmin
Biomark Insights · 2024 · PMID 39314258 · Full text
BACKGROUND: Hypoxia, a condition where there is a lack of oxygen, is known to play a role in cancer progression. OBJECTIVE: This study investigates the correlation between gene-altered expression and hypoxia in Banglade...
BACKGROUND: Hypoxia, a condition where there is a lack of oxygen, is known to play a role in cancer progression. OBJECTIVE: This study investigates the correlation between gene-altered expression and hypoxia in Bangladeshi breast cancer (BC) cases and TCGA_BC datasets. DESIGN: This case-control study compares BC cases to healthy controls to understand the relationship between gene changes and cancer. METHOD: This study used advanced analysis methods to examine the transcriptional landscape of BC, and quantitatively assessed its correlation using integrated multi-omics analysis. RESULTS: In Bangladeshi BC cases, the T allele of rs1154946 correlates notably (-value < .001) with BC incidence. ELISA results confirmed a significant association (-value < .005) between elevated expression and BC-related hypoxia. Bioinformatics eQTL analysis validated the correlation between increased expression and rs11549465 T allele (-value < .01). Structural analyses suggested that rs11549465 (P582S) mutation may decrease protein stability (ΔΔG-value: -1.24 kcal/mole), potentially affecting function. enrichment analysis in BC underscores strong associations with oxygen levels, hypoxia, metabolic processes, apoptosis, and programed cell death (-value < .001). Transcriptomic data demonstrated a robust correlation (-value < .0001) between expression and copy-number alterations, mutations, and abnormal methylation. Altered expression showed strong negative correlations (-value < .00001) with methylation and the expression of the ER (), in Whites. Survival analysis revealed marked differences in overall survival linked to high and low expression (-value < .00001). Furthermore, expression significantly correlated (-value < .000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment. CONCLUSION: Thus, the gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation.
Correlation Analyses Between Serum Interleukin-7, Interleukin-15 and Lactate Provide Insights Into Their Potential Roles in the Regulation of Inflammation in Elderly Septic Patients.
Zhao J, Zhang Y, Wang JY … +2 more , Wei B, Liu YG
Biomark Insights · 2024 · PMID 39257715 · Full text
BACKGROUND: Our previous research have identified Interleukin (IL)-7 and IL-15 as prognostic biomarkers for elderly septic patients, however, little is known about the link between the serum levels of IL-7, IL-15, and la...
BACKGROUND: Our previous research have identified Interleukin (IL)-7 and IL-15 as prognostic biomarkers for elderly septic patients, however, little is known about the link between the serum levels of IL-7, IL-15, and lactate as well as their potential roles in the regulation of inflammation in elderly septic patients. OBJECTIVES: This study aimed at investigating the link between the serum levels of IL-7, IL-15, and lactate as well as with other factors in elderly septic patients. DESIGN: This is a retrospective study including 129 elderly patients with sepsis who were divided into the survival group (N = 34) and the nonsurvival group (N = 95) and further subgrouped based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. METHODS: The baseline data and clinical parameters were recorded within 24 h upon admission. Serum levels of the cytokines were quantified by the Luminex assay. Spearman correlation analysis were performed. RESULTS: Serum levels of IL-6, IL-7, IL-15, and tumor necrosis factor-α (TNF-α) were significantly higher in the nonsurvival group ( < .05). Correlations between serum levels of IL-7 and platelet-derived growth factor-AA (PDGF-AA), as well as correlations between IL-15, IL-6, and TNF-α were confirmed ( < .05). Both the serum levels of lactate and IL-15 correlated with the total counts of platelet (PLT) in the survival subgroup with low APACHE Ⅱ scores while the serum levels of IL-7, IL-15, and total counts of monocytes correlated with each other in the nonsurvival subgroup with different APACHE Ⅱ scores ( < .05). CONCLUSION: Knowledge of the regulation networks between serum levels of IL-7, IL-15, lactate, and other cytokines may provide insights into potential mechanisms in the modulation of inflammation in elderly septic patients and facilitate more prompt and accurate treatment to reduce the mortality rate.
Characterization of RNA Processing Genes in Colon Cancer for Predicting Clinical Outcomes.
Hu J, Ning Y, Ma Y … +2 more , Sun L, Chen G
Biomark Insights · 2024 · PMID 39161926 · Full text
OBJECTIVE: Colon cancer is associated with multiple levels of molecular heterogeneity. RNA processing converts primary transcriptional RNA to mature RNA, which drives tumourigenesis and its maintenance. The characterisat...
OBJECTIVE: Colon cancer is associated with multiple levels of molecular heterogeneity. RNA processing converts primary transcriptional RNA to mature RNA, which drives tumourigenesis and its maintenance. The characterisation of RNA processing genes in colon cancer urgently needs to be elucidated. METHODS: In this study, we obtained 1033 relevant samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the heterogeneity of RNA processing phenotypes in colon cancer. Firstly, Unsupervised hierarchical cluster analysis detected 4 subtypes with specific clinical outcomes and biological features via analysis of 485 RNA processing genes. Next, we adopted the least absolute shrinkage and selection operator (LASSO) as well as Cox regression model with penalty to characterise RNA processing-related prognostic features. RESULTS: An RNA processing-related prognostic risk model based on 10 genes including , , , , , , , , , and was identified finally. A composite prognostic nomogram was constructed by combining this feature with the remaining clinical variables including TNM, age, sex, and stage. Genetic variation, pathway activation, and immune heterogeneity with risk signatures were also analysed via bioinformatics methods. The outcomes indicated that the high-risk subgroup was associated with higher genomic instability, increased proliferative and cycle characteristics, decreased tumour killer CD8 T cells and poorer clinical prognosis than the low-risk group. CONCLUSION: This prognostic classifier based on RNA-edited genes facilitates stratification of colon cancer into specific subgroups according to TNM and clinical outcomes, genetic variation, pathway activation, and immune heterogeneity. It can be used for diagnosis, classification and targeted treatment strategies comparable to current standards in precision medicine. It provides a rationale for elucidation of the role of RNA editing genes and their clinical significance in colon cancer as prognostic markers.
Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation.
Urbiola-Salvador V, Jabłońska A, Miroszewska D … +25 more , Kamysz W, Duzowska K, Drężek-Chyła K, Baber R, Thieme R, Gockel I, Zdrenka M, Śrutek E, Szylberg Ł, Jankowski M, Bała D, Zegarski W, Nowikiewicz T, Makarewicz W, Adamczyk A, Ambicka A, Przewoźnik M, Harazin-Lechowska A, Ryś J, Macur K, Czaplewska P, Filipowicz N, Piotrowski A, Dumanski JP, Chen Z
Biomark Insights · 2024 · PMID 38911905 · Full text
BACKGROUND: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and h...
BACKGROUND: Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. OBJECTIVE AND DESIGN: This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. RESULTS: Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. CONCLUSION: Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
Navigating the Intricacies of Tumor Heterogeneity: An Insight into Potential Prognostic Breast Cancer Biomarkers.
Altriche N, Gallant S, Augustine TN … +1 more , Xulu KR
Biomark Insights · 2024 · PMID 38895160 · Full text
Breast cancer is a heterogeneous disease with diverse histological and molecular subtypes. Luminal breast tumors are the most diagnosed subtype. In luminal breast cancer, hormone receptors (including ER, PR, HER2) play a...
Breast cancer is a heterogeneous disease with diverse histological and molecular subtypes. Luminal breast tumors are the most diagnosed subtype. In luminal breast cancer, hormone receptors (including ER, PR, HER2) play a diagnostic and prognostic role. Despite the effectiveness of endocrine therapy in luminal breast tumors, tumor recurrence and resistance occur, and this may highlight evolutionary strategies for survival driven by stemness. In this review we thus consider the association between estrogen signaling and stemness in mediating tumor processes. Many studies report stemness as one of the factors promoting tumor progression. Its association with estrogen signaling warrants further investigation and provides an opportunity for the identification of novel biomarkers which may be used for diagnostic, prognostic, and therapeutic purposes. Breast cancer stem cells have been characterized (CD44 CD24) and their role in promoting treatment resistance and tumor recurrence widely studied; however, the complexity of tumor progression which also involve microenvironmental factors suggests the existence of more varied cell phenotypes which mediate stemness and its role in tumor progression.
Genetic Association Between Polycystic Ovary Syndrome and the rs662799 and rs894160 Metabolic Variants in the Western Saudi Population: A Case-Control Study.
Bakhashab S, Batarfi AA, Alhartani MM … +2 more , Turki R, Mady W
Biomark Insights · 2024 · PMID 38887365 · Full text
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS pathogenesis is complex and multifactorial, in...
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS pathogenesis is complex and multifactorial, involving genetic and environmental factors. OBJECTIVES: This study aimed to determine and compare genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (; rs662799) and perilipin 1 (; rs894160, rs1052700 and rs6496589) genes in Western Saudi women to investigate their association with PCOS and its clinical characteristics. DESIGN AND METHODS: This was a case-control study conducted on women with ( = 104) and without ( = 87) PCOS. The SNPs were genotyped using TaqMan genotyping assays. RESULTS: Significant and direct associations were detected between PCOS susceptibility and SNP rs662799 and SNP rs894160 ( < .001). For SNP rs662799, women with the A allele were more likely to have PCOS (relative risk [RR] = 1.348, odds ratio [OR] = 2.313, < .001) and hypertriglyceridaemia (OR = 17.0, = .5) than women with the G allele. For SNP rs894160, women with the T allele were more likely to have PCOS than women with the C allele (RR = 8.043, OR = 7.427, < .001). For SNP rs1052700, women with the TT genotype were more likely to have hyperandrogenism (OR = 29.75, = .02) and an irregular period (OR = 0.07, = .040) than women with the AT genotype. CONCLUSION: We identified novel alleles and genotypes contributing to the genetic risk of PCOS in the Western Saudi population.
Novel Serum Proteomes Expressed from Benzene Exposure Among Gasoline Station Attendants.
Polyong CP, Roytrakul S, Sirivarasai J … +2 more , Yingratanasuk T, Thetkathuek A
Biomark Insights · 2024 · PMID 38868168 · Full text
BACKGROUND: Research on the proteomes impact of benzene exposure in fuel station employees remains sparse, underscoring the need for detailed health impact assessments focusing on biomarker evaluation. OBJECTIVES: This i...
BACKGROUND: Research on the proteomes impact of benzene exposure in fuel station employees remains sparse, underscoring the need for detailed health impact assessments focusing on biomarker evaluation. OBJECTIVES: This investigation aimed to analyze the differences in blood parameters and serum proteomes resulting from benzene exposure between gasoline station attendants (B-GSA) and a control group. DESIGN AND METHODS: A cross-sectional analytical study was conducted with 96 participants, comprising 54 in the B-GSA group and 42 in the control group. The methodology employed included an interview questionnaire alongside urine and blood sample collections. The urine samples were analyzed for -muconic acid (-MA) levels, while the blood samples underwent complete blood count analysis and proteome profiling. RESULTS: Post-shift analysis indicated that the B-GSA group exhibited significantly higher levels of -MA and monocytes compared to the control group ( < .05). Proteome quantification identified 1448 proteins differentially expressed between the B-GSA and control groups. Among these, 20 proteins correlated with the levels of -MA in urine. Notably, 4 proteins demonstrated more than a 2-fold down-regulation in the B-GSA group: HBS1-like, non-structural maintenance of chromosomes element 1 homolog, proprotein convertase subtilisin/kexin type 4, and zinc finger protein 658. The KEGG pathway analysis revealed associations with apoptosis, cancer pathways, p53 signaling, and the TNF signaling pathway. CONCLUSION: The changes in these 4 significant proteins may elucidate the molecular mechanisms underlying benzene toxicity and suggest their potential as biomarkers for benzene poisoning in future assessments.
Association of 10 Polymorphisms in PLA2R1 and HLA DQA1 Genes with Primary Membranous Nephropathy Risk: A Meta-Analysis and a Meta-Regression.
Dhaouadi T, Riahi A, Abdallah TB … +2 more , Gorgi Y, Sfar I
Biomark Insights · 2024 · PMID 38863528 · Full text
BACKGROUND: Although, several studies have assessed the association of the phospholipase A2 receptor (PLA2R) and HLA-DQA1 SNPs with primary membranous nephropathy (PMN), results were inconsistent and between-studies hete...
BACKGROUND: Although, several studies have assessed the association of the phospholipase A2 receptor (PLA2R) and HLA-DQA1 SNPs with primary membranous nephropathy (PMN), results were inconsistent and between-studies heterogeneity needs to be investigated. OBJECTIVES: The aim of this review was to summarize existing data on the contribution of 10 SNPs in the PLA2R and HLA-DQA1 genes to PMN susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions. DESIGN: This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses. DATA SOURCES AND METHODS: An electronic literature search for eligible studies among all papers published prior to January 10, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the 10 following SNPs: rs4664308, rs3749117, rs3749119, rs35771982, rs3828323, rs16844715, rs1511223, rs6757188, rs2715918, and rs2187668. RESULTS: Combined analyses revealed a significant increase in PMN risk conferred by the following alleles: rs4664308*A, rs3749117*T, rs3749119*C, rs35771982*G, rs3828323*C, rs16844715*C, rs1511223*A, rs2715918*A, and rs2187668*A, all -values < .001. Moreover, the PLA2R-rs4664308/HLA-DQA1-rs2187668 interaction was significantly associated with an increased PMN risk, < .001. However, there was a substantial between-studies heterogeneity for some SNPs. Subgroup analyses by ethnicity for the 9 PLA2R SNPs did not show any cross-ethnic disparity. Inversely, the risk conferred by the HLA-DQA1 rs2187668*A allele was significantly higher in Caucasians (OR [95% CI] = 3.929 [3.251-4.748]) than in Asians (OR [95% CI] = 2.537 [1.94-3.318], = .007. Besides, meta-regressions revealed for the majority of investigated SNPs significant correlations of the effect size with albumin, 24-hours proteinuria, serum creatinine, and eGFR levels. Hence, the influence on PMN risk conferred by the PLA2R and HLA-DQA1 SNPs was rather noted in patients with a severe disease. CONCLUSION: This meta-analysis showed that 9 out of the 10 investigated SNPs in PLA2R and HLA-DQA1 genes were associated with increased PMN risk. Heterogeneity could be due to disparate patient groups in terms of disease presentation for almost all SNPs, and ethnicity for the HLA-DQA1 rs2187668 SNP. REGISTRATION: This review has been registered on PROSPERO: CRD42024506729. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506729.
MicroRNAs in Umbilical Cord Blood and Development in Full-Term Newborns: A Prospective Study.
Wang LJ, Tsai CC, Chao HR … +3 more , Lee SY, Chen CC, Li SC
Biomark Insights · 2024 · PMID 38863527 · Full text
BACKGROUND: Exploring the epigenetic regulations, such as microRNA, in newborns holds significant promise for enhancing our ability to address and potentially prevent early-life developmental delays. OBJECTIVES: Hence, t...
BACKGROUND: Exploring the epigenetic regulations, such as microRNA, in newborns holds significant promise for enhancing our ability to address and potentially prevent early-life developmental delays. OBJECTIVES: Hence, this research seeks to investigate if the expression of miRNA in the umbilical cord blood of infants can forecast their developmental outcomes as they grow older. DESIGN AND METHOD: We enrolled 143 full-term newborns, delivered either via cesarean section (CS) or through natural spontaneous delivery (NSD). We then analyzed the profiles of specific miRNAs (miR-486-5p, miR-126-5p, miR-140-3p, miR-151a-3p, miR-142-5p, and miR-30e-5p) in the umbilical cord blood of these infants. Subsequently, we performed follow-up assessments using Bayley-III scores when the cohort reached 1 year of age. Furthermore, we conducted pathway-enrichment analyses on the target genes associated with these examined miRNAs. RESULTS: When comparing newborns delivered via cesarean section (CS) to those born via natural spontaneous delivery (NSD), we observed notable differences. Specifically, newborns through NSD displayed significantly higher ΔCt values for miR-486-5p, alongside lower ΔCt values for miR-126-5p and miR-151a-3p in their cord blood. At 1 year of age, cognitive development was significantly linked to the ΔCt values of miR-140-3p and miR-142-5p, while language development showed a significant association with the ΔCt values of miR-140-3p. Moreover, our pathway enrichment analyses revealed that the target genes of these miRNAs were consistently involved in the pathways related to neurons, such as axon guidance and the neurotrophin signaling pathway. CONCLUSION: In summary, this study represents a pioneering effort in elucidating the potential connections between miRNA levels in cord blood and the health indicators and neurodevelopment of newborns at 1 year of age. Our findings underscore the significance of miRNA levels at birth in influencing mechanisms related to neurodevelopment.
Effect of Cytokeratin-18, C-peptide, MHR, and MACK-3 Biomarkers in Metabolic Dysfunction-Associated Fatty Liver Disease After Laparoscopic Sleeve Gastrectomy.
Hany M, Demerdash HM, Abouelnasr AA … +1 more , Torensma B
Biomark Insights · 2024 · PMID 38836118 · Full text
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has emerged as a valuable treatment for various metabolic disorders, including metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with obesity. Cons...
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has emerged as a valuable treatment for various metabolic disorders, including metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with obesity. Consequently, there is a pressing need to develop noninvasive biomarkers for diagnosing and monitoring disease progression. OBJECTIVES: This study aimed to evaluate specific biomarkers, including Cytokeratin-18 (CK-18), C-peptide, monocyte to HDL cholesterol ratio (MHR), and MACK-3, in patients with obesity with MAFLD undergoing LSG. DESIGN: A prospective cohort study on patients with obesity before and 6 months after the LSG procedure. METHODS: 70 patients with obesity with confirmed MAFLD, determined by Transient Elastography (TE), were pre- and 6 months postoperatively tested. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), lipid profile, ghrelin, leptin, peptide YY, GLP-1, and liver fibrosis scores, including AST/ALT ratio (AAR), Fibrosis-4 index (FIB-4), and BARD Score were tested. RESULTS: BMI significantly decreased in all participants, with a % excess weight loss of 62.0% ± 15.4%. TE measurements revealed a significant postoperative reduction from 100% to 87.1% ( = .006). All selected biomarkers showed significant postoperative improvement-a significant association of CK-18 with MAFLD markers, including AAR, FIB-4, and BARD score, were found. MACK-3 had positive associations with FIB-4. C-peptide and MHR showed no association with MAFLD markers. Furthermore, there was a positive correlation between CK-18 and MACK-3 tests and between C-peptide and CK-18 and MACK-3. Additionally, a receiver operating characteristic (ROC) curve was constructed, with CK-18 performing the best, with an estimated area under the curve of 0.863. CONCLUSION: Serum CK-18 outperformed other selected biomarkers in predicting and monitoring MAFLD in patients with obesity, suggesting its prospective utility in clinical practice. Further studies are needed to validate the accuracy of the MACK-3 test.
Are We Using Ezetimibe As Much As We Should?
Manolis AA, Manolis TA, Mikhailidis DP … +1 more , Manolis AS
Biomark Insights · 2024 · PMID 38827240 · Full text
Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lip...
Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance.
The Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers.
Seema Mustafa, Jansen CS, Jani Y … +6 more , Evans S, Zhuang TZ, Brown J, Nazha B, Master V, Bilen MA
Biomark Insights · 2024 · PMID 38827239 · Full text
In the past decade, immune checkpoint inhibitors (ICI) have been approved for treatment of genitourinary malignancies and have revolutionized the treatment landscape of these tumors. However, despite the remarkable succe...
In the past decade, immune checkpoint inhibitors (ICI) have been approved for treatment of genitourinary malignancies and have revolutionized the treatment landscape of these tumors. However, despite the remarkable success of these therapies in some GU malignancies, many patients' tumors do not respond to these therapies, and others may experience significant side effects, such as immune-related adverse events (iRAEs). Accordingly, biomarkers and improved prognostic tools are critically needed to help predict which patients will respond to ICI, predict and mitigate risk of developing immune-related adverse events, and inform personalized choice of therapy for each patient. Ongoing clinical and preclinical studies continue to provide an increasingly robust understanding of the mechanisms of the response to immunotherapy, which continue to inform biomarker development and validation. Herein, we provide a comprehensive review of biomarkers of the response to immunotherapy in GU tumors and their role in selection of therapy and disease monitoring.
Comparative Analysis of Biomarkers in Type 2 Diabetes Patients With and Without Comorbidities: Insights Into the Role of Hypertension and Cardiovascular Disease.
Savvopoulos S, Hatzikirou H, Jelinek HF
Biomark Insights · 2024 · PMID 38707193 · Full text
BACKGROUND: Type 2 diabetes mellitus (T2DM) are 90% of diabetes cases, and its prevalence and incidence, including comorbidities, are rising worldwide. Clinically, diabetes and associated comorbidities are identified by...
BACKGROUND: Type 2 diabetes mellitus (T2DM) are 90% of diabetes cases, and its prevalence and incidence, including comorbidities, are rising worldwide. Clinically, diabetes and associated comorbidities are identified by biochemical and physical characteristics including glycemia, glycated hemoglobin (HbA1c), and tests for cardiovascular, eye and kidney disease. OBJECTIVES: Diabetes may have a common etiology based on inflammation and oxidative stress that may provide additional information about disease progression and treatment options. Thus, identifying high-risk individuals can delay or prevent diabetes and its complications. DESIGN: In patients with or without hypertension and cardiovascular disease, as part of progression from no diabetes to T2DM, this research studied the changes in biomarkers between control and prediabetes, prediabetes to T2DM, and control to T2DM, and classified patients based on first-attendance data. Control patients and patients with hypertension, cardiovascular, and with both hypertension and cardiovascular diseases are 156, 148, 61, and 216, respectively. METHODS: Linear discriminant analysis is used for classification method and feature importance, This study examined the relationship between Humanin and mitochondrial protein (MOTSc), mitochondrial peptides associated with oxidative stress, diabetes progression, and associated complications. RESULTS: MOTSc, reduced glutathione and glutathione disulfide ratio (GSH/GSSG), interleukin-1β (IL-1β), and 8-isoprostane were significant ( < .05) for the transition from prediabetes to t2dm, highlighting importance of mitochondrial involvement. complement component 5a (c5a) is a biomarker associated with disease progression and comorbidities, gsh gssg, monocyte chemoattractant protein-1 (mcp-1), 8-isoprostane being most important biomarkers. CONCLUSIONS: Comorbidities affect the hypothesized biomarkers as diabetes progresses. Mitochondrial oxidative stress indicators, coagulation, and inflammatory markers help assess diabetes disease development and provide appropriate medications. Future studies will examine longitudinal biomarker evolution.
Evaluating the Role of Methylated Circulating Tumor DNA in Combination With Pathological Prognostic Factors for Predicting Recurrence of Colorectal Cancer.
Al Naji H, Winter JM, Pedersen SK … +4 more , Roy A, Byrne SE, Young GP, Symonds EL
Biomark Insights · 2024 · PMID 38426070 · Full text
BACKGROUND: Colorectal cancer (CRC) has a high rate of recurrence, in particular for advanced disease, but prognosis based on staging and pathology at surgery can have limited efficacy. The presence of circulating tumor...
BACKGROUND: Colorectal cancer (CRC) has a high rate of recurrence, in particular for advanced disease, but prognosis based on staging and pathology at surgery can have limited efficacy. The presence of circulating tumor DNA (ctDNA) at diagnosis could be used to improve the prediction for disease recurrence. OBJECTIVES: To assess the impact of detecting methylated ctDNA at diagnosis in combination with demographic, lifestyle, clinical factors and tumor pathology, to assess predictive value for recurrence. DESIGN: A retrospective cohort study. METHODS: The cohort included 180 patients (36 with recurrent CRC), who had undergone complete treatment and surveillance for a minimum of 3 years. Participant clinical details and ctDNA methylated / results were compared between those with and without recurrence, and cox regression analysis assessed each factor on disease-free survival. RESULTS: Clinical factors independently associated with reduced disease-free survival included nodal involvement (HR = 3.83, 95% CI 1.56-9.43, = .003), M1 stage (HR = 4.41, 95% CI 1.18-16.45, = .027), a resection margin less than 2 mm (HR = 4.60, 95% CI 1.19-17.76, = .027), perineural involvement (HR = 2.50, 95% CI 1.01-6.17, = .047) and distal tumors (HR = 3.13, 95% CI 1.07-9.18, = .037). Methylated / was detected in 51.7% (93/180) of pre-treatment plasma samples. When a positive ctDNA finding was considered in combination with these clinical prognostic factors, there was improved predictive power of recurrence for patients with perineural involvement (HR = 4.44, 95% CI 1.92-10.26, < .001), and it marginally improved the predictive factor for M1 stage (HR = 7.59, 95% CI 2.30-25.07, = .001) and distal tumors (HR = 5.04, 95% CI 1.88-13.49, = .001). CONCLUSIONS: Nodal invasion, metastatic disease, distal tumor site, low resection margins and perineural invasion were associated with disease recurrence. Pre-treatment methylated ctDNA measurement can improve the predictive value for recurrence in a subset of patients, particularly those with perineural involvement. REGISTRATION: Australian and New Zealand Clinical Trials Registry #12611000318987.
mRNA Expression and Methylation of the , , , , and Genes in Gastric Adenocarcinoma.
Pádua JDB, Mariano CFA, Fabro AT … +10 more , Lizarte Neto FS, Zuliani RL, Sares CTG, Dos Santos JS, Sankarankutty AK, Tirapelli DPDC, Silveira VDS, de Molfetta GA, Júnior WADS, Brunaldi MO
Biomark Insights · 2024 · PMID 38293680 · Full text
BACKGROUND: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers. OBJECTIVE AND DESIGN...
BACKGROUND: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers. OBJECTIVE AND DESIGN: This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm. METHODS: We evaluated mRNA expression and methylation of , , , , and in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features. RESULTS: , , , , and mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: with ( = .027), ( < .001), and ( < .001); with ( = .007), and ( = .001); with ( = 0.001). mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, = .015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, = .035). Greater tumoral mRNA levels correlated with perineural invasion (1.822 vs 0.725, = .010) and death (1.664 vs 0.929, = .036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, = .032), and no significant correlation for the other markers. CONCLUSIONS: Our results suggest , , and methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced expression participates in disease progression, and show an association between mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for , can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated.
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