Pharmacogenomics And Personalized Medicine[JOURNAL]
Sun
200 papers
Circ_0000140 Alters miR-527/SLC7A11-Mediated Ferroptosis to Influence Oral Squamous Cell Carcinoma Cell Resistance to DDP.
Ma Y, Gao J, Guo H
Pharmgenomics Pers Med · 2023 · PMID 38105907 · Full text
BACKGROUND: While there is prior evidence for the ability of circular RNAs (circRNAs) to shape the cisplatin (DDP) resistance of cancers in human patients, there has been relatively little research to date focused on the...
BACKGROUND: While there is prior evidence for the ability of circular RNAs (circRNAs) to shape the cisplatin (DDP) resistance of cancers in human patients, there has been relatively little research to date focused on the interplay between circRNAs and DDP resistance in the context of OSCC progression to date. In the present analysis, the functional role that circ_0000140 plays as a mediator of chemoresistance to DDP was thus explored in greater detail. METHODS: Both qPCR and Western immunoblotting were employed as appropriate to detect circ_0000140, miR-527, and SLC7A11 levels, while interactions among these factors were detected through RNA immunoprecipitation, RNA pull-down, and dual luciferase report assays. MTT assays were used to assess cellular viability as a means of gauging DDP sensitivity. RESULTS: Both tissue samples from DDP-resistant OSCC patient tumors and OSCC cell lines resistant to DDP exhibited pronounced circ_0000140 upregulation. Knocking down this circRNA significantly increased the DDP sensitivity of both tested DDP-resistant OSCC cell lines and promoted ferroptosis, whereas knocking down miR-527 was sufficient to reverse these effects, which were recapitulated by miR-527 overexpression. Conversely, the effects of overexpressing miR-527 were reversed by the restoration of SLC7A11 expression. Consistently, this circRNA was able to increase DDP IC50 values and to suppress ferroptosis in both tested cell lines through this miR-527/SLC7A11 signaling axis. CONCLUSION: These results revealed that circ_0000140/miR-527/SLC7A11-mediated ferroptosis may provide novel insights into the development of this cancer type and the emergence of chemoresistance in the future.
A Review on Probable Causes of Cardiotoxicity Caused by Common Cancer Drugs and the Role of Traditional Chinese Medicine in Prevention and Treatment.
Zhou M, Wang W, Weng J … +1 more , Lai Z
Pharmgenomics Pers Med · 2023 · PMID 38084311 · Full text
Cancer is a widespread disease in our nation, characterized by a high occurrence rate. The use of tumor medications has been linked to an increased chance of cardiovascular complications, including a notable occurrence o...
Cancer is a widespread disease in our nation, characterized by a high occurrence rate. The use of tumor medications has been linked to an increased chance of cardiovascular complications, including a notable occurrence of heart toxicity. This has caused significant concern among healthcare professionals. This article provides a comprehensive compilation of drugs recognized for their potential to cause heart toxicity. Furthermore, extensive research has been conducted to investigate and categorize the effects of heart toxicity, with the purpose of promoting awareness, facilitating early intervention, and ultimately reducing the occurrence of heart toxicity. At the same time, there is an anticipation that Traditional Chinese Medicine (TCM) can capitalize on its unique attributes to address such ailments. To establish its effectiveness, it is crucial to carry out extensive clinical trials or retrospective analyses. The purpose of this article is to summarize the possible mechanisms of cardiac toxicity caused by commonly used chemotherapy drugs and summarize the possible mechanisms of adverse cardiac toxicity, laying the groundwork for subsequent research.
Novel Autophagy-Related Blood Biomarkers Associated with Immune Cell Infiltration in Ankylosing Spondylitis.
Song H, Liu H, Li X … +5 more , Lv B, Tang Z, Chen Q, Zhang D, Wang F
Pharmgenomics Pers Med · 2023 · PMID 38073713 · Full text
BACKGROUND: This study aims to identify new therapeutic targets and explore the molecular mechanism of ankylosing spondylitis (AS), a rheumatic immune disease that mainly affects the sacroiliac and spinal joints. Despite...
BACKGROUND: This study aims to identify new therapeutic targets and explore the molecular mechanism of ankylosing spondylitis (AS), a rheumatic immune disease that mainly affects the sacroiliac and spinal joints. Despite extensive research, the exact cause of AS is still unknown. The research team utilized a bioinformatics approach to achieve their objectives. METHODS: The GSE73754 dataset was downloaded from GEO database. Autophagy-related genes (ARGs) were collected from the Human Autophagy-dedicated Database. The limma package was used to screen for differentially expressed genes (DEGs), which were then intersected with the autophagy-related genes (ARGs) to identify differentially expressed autophagy-related genes (DEARGs). Subsequently, the DEARGs associated with AS were subjected to GO-BP and KEGG enrichment analyses using the clusterProfiler package. Core genes were identified using the cytoHubba plug-in of Cytoscape and were validated by clinical blood samples. Additionally, the Cell algorithm was utilized to evaluate the proportion of immune cell infiltration. RESULTS: A total of 29 DEARGs were identified, which were found to be mainly enriched in autophagy, apoptosis, and necroptosis through functional enrichment analysis. Two core genes, HSPA5 and SQSTM1, were confirmed to have diagnostic value in AS. Immune cell infiltration analysis revealed CD8+ T cells, CD8+ T effector memory (Tem), natural killer (NK) cells, T gamma delta (Tgd) cells, and T-helper 1 (Th1) cells as major participants in AS development. Furthermore, HSPA5 expression was significantly correlated with Th1 cells, CD8+ T cells, CD4+ memory cells, and macrophages. CONCLUSION: This study suggested that HSPA5 and SQSTM1 can serve as useful diagnostic biomarkers for AS. These findings lay the foundation for identifying crucial mRNAs in the whole blood of AS patients, which may aid in the development of novel markers for AS.
Identification of P3H1 as a Predictive Prognostic Biomarker for Bladder Urothelial Carcinoma Based on the Cancer Genome Atlas Database.
Zhang Y, Chen Y, Chen Z … +5 more , Zhou X, Chen S, Lan K, Wang Z, Zhang Y
Pharmgenomics Pers Med · 2023 · PMID 38058295 · Full text
PURPOSE: The extracellular matrix in the tumor microenvironment are closely related to the development of tumors. This study's primary aim is to study the association between prolyl 3-hydroxylase 1 (P3H1) which mainly ex...
PURPOSE: The extracellular matrix in the tumor microenvironment are closely related to the development of tumors. This study's primary aim is to study the association between prolyl 3-hydroxylase 1 (P3H1) which mainly expresses collagen in extracellular matrix and the progression and prognosis of bladder cancer (BC). METHODS: The clinical and transcriptome data were acquired from the cancer genome atlas database. BLCAsubtyping is used to evaluate tissue subtypes of BC. The COX proportional hazards can be used to evaluate the survival process's influencing factors. Immunohistochemistry was used to identify differences in the expression of P3H1 in cancer and paired adjacent tissues. GSEA was used to investigate the underlying biological processes. Finally, ssGSEA, TIMER and pRRophetic were used to study the relationship between P3H1 and immune cell infiltration and drug sensitivity. RESULTS: The expression of P3H1 was substantially higher in highly invasive BC samples than in low invasive BC. P3H1 was an independent predictor of overall survival (HR = 1.12, = 0.03). P3H1 expression was significantly higher in tumor tissues than adjacent normal tissues in clinical tissue samples, and was significantly higher in highly stage cancer than low stage cancer samples. Samples with high P3H1 expression had a higher level of immune cell infiltration and immune function, as well as a significant correlation with macrophage and dendritic cell infiltration and TGF-beta, Th1 cells, and macrophage regulation (cor >0.3, p <0.05). P3H1 high expression samples were substantially more sensitive to docetaxel, cisplatin, vinblastine, camptothecin, paclitaxel, and other medicines than P3H1 low expression samples. DISCUSSION: P3H1 is a possible oncogene and an independent predictor of poor prognosis in BC; it also has enhanced sensitivity to docetaxel, cisplatin, vinblastine, camptothecin, paclitaxel, and other medications.
Implication of KDR Polymorphism rs2071559 on Therapeutic Outcomes and Safety of Postoperative Patients with Gastric Cancer Who Received S-1-Based Adjuvant Chemotherapy: A Real-World Exploratory Study.
Meng L, Cao J, Kang L … +4 more , Xu G, Yuan DW, Li K, Zhu K
Pharmgenomics Pers Med · 2023 · PMID 38046381 · Full text
OBJECTIVE: Regimens of S-1-based adjuvant chemotherapy are of great significance in attenuating recurrence risk in postoperative patients with gastric cancer (GC). Kinase insert-domain receptor (KDR) gene plays an essent...
OBJECTIVE: Regimens of S-1-based adjuvant chemotherapy are of great significance in attenuating recurrence risk in postoperative patients with gastric cancer (GC). Kinase insert-domain receptor (KDR) gene plays an essential role in tumor growth and metastasis. This study aimed to investigate the implication of KDR genotyping on the therapeutic outcomes of patients with gastric cancer (GC) who received S-1-based adjuvant chemotherapy. METHODS: A total of 169 postoperative GC with pathological staging of II and III and no metastasis who received S-1-based adjuvant chemotherapy were included retrospectively. Peripheral blood specimens were collected and prepared for KDR genotyping and KDR mRNA expression. Correlation between KDR genotype status and prognosis was performed using Kaplan-Meier survival analysis, and multivariate analysis was ultimately adopted using Cox regression analysis. RESULTS: Median disease-free survival (DFS) of the 169 patients with GC was 5.1 years [95% confidence interval (CI): 4.25-5.95] and median overall survival (OS) was 6.7 years (95% CI: 5.44-7.96). Rs2071559 was located at the upstream region, and the prevalence among 169 patients with GC was as follows: AA genotype in 104 cases (61.5%), AG genotype in 57 cases (33.7%), and GG genotype in 8 cases (4.7%), yielding a minor allele frequency of 0.22, which was consistent with Hardy-Weinberg equilibrium (=0.958). Median DFS of patients with AA and AG/GG genotypes was 6.0 years and 4.0 years, respectively (=0.002). Additionally, patients with the AA genotype had longer OS than those with the AG/GG genotype [median OS: not reached (NR) vs 5.5 years, =0.011]. Additionally, KDR mRNA expression was significantly higher in patients with the AG/GG genotype than that in those with the AA genotype (<0.001). CONCLUSION: Rs2071559 in KDR gene might be a promising biomarker for evaluating the recurrence risk and OS of patients with GC who received S-1-based adjuvant chemotherapy. This conclusion should be confirmed in randomized clinical trials.
Identification of a Prognostic Gene Signature Based on Lipid Metabolism-Related Genes in Esophageal Squamous Cell Carcinoma.
Shen GY, Yang PJ, Zhang WS … +4 more , Chen JB, Tian QY, Zhang Y, Han B
Pharmgenomics Pers Med · 2023 · PMID 38023824 · Full text
BACKGROUND: Dysregulation of lipid metabolism is common in cancer. However, the molecular mechanism underlying lipid metabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are not wel...
BACKGROUND: Dysregulation of lipid metabolism is common in cancer. However, the molecular mechanism underlying lipid metabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are not well understood. The objective of our study was to construct a lipid metabolism-related prognostic model to improve prognosis prediction in ESCC. METHODS: We downloaded the mRNA expression profiles and corresponding survival data of patients with ESCC from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We performed differential expression analysis to identify differentially expressed lipid metabolism-related genes (DELMGs). We used Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to establish a risk model in the GEO cohort and used data of patients with ESCC from the TCGA cohort for validation. We also explored the relationship between the risk model and the immune microenvironment via infiltrated immune cells and immune checkpoints. RESULTS: The result showed that 132 unique DELMGs distinguished patients with ESCC from the controls. We identified four genes (ACAA1, ACOT11, B4GALNT1, and DDHD1) as prognostic gene expression signatures to construct a risk model. Patients were classified into high- and low-risk groups as per the signature-based risk score. We used the receiver operating characteristic (ROC) curve and the Kaplan-Meier (KM) survival analysis to validate the predictive performance of the 4-gene signature in both the training and validation sets. Infiltrated immune cells and immune checkpoints indicated a difference in the immune status between the two risk groups. CONCLUSION: The results of our study indicated that a prognostic model based on the 4-gene signature related to lipid metabolism was useful for the prediction of prognosis in patients with ESCC.
Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with Protein Tyrosine Phosphatase Non-Receptor Type 11 Gene Mutation.
Huang R, Zhang YT, Lin Y … +3 more , Pang RL, Yang Z, Zhao WH
Pharmgenomics Pers Med · 2023 · PMID 38023823 · Full text
OBJECTIVE: The purpose of our study was to investigate the clinical characteristics, molecular biological characteristics and prognosis of acute myeloid leukemia (AML) patients with protein tyrosine phosphatase non-recep...
OBJECTIVE: The purpose of our study was to investigate the clinical characteristics, molecular biological characteristics and prognosis of acute myeloid leukemia (AML) patients with protein tyrosine phosphatase non-receptor type 11 (PTPN11) gene mutation. METHODS: The clinical data of 30 newly diagnosed adult AML patients with PTPN11 gene mutation were analyzed retrospectively. Kaplan-Meier and Cox proportional risk regression model were examined for prognostic analysis and prognostic factor screening. RESULTS: High-frequency mutation sites of PTPN11 gene are located in exon 3 of chromosome 12, which are D61 and A72 (16.7%), followed by E76 (13.3%). The median variant allele frequency (VAF) of PTPN11 mutant gene is 18.4%. The patients were divided into two groups according to PTPN11 VAF 35.3% (upper quartile). We observed that the peripheral blood leukocyte count in patients with VAF ≥35.3% was significantly higher than patients with VAF < 35.3% (p = 0.019) and also closely related to M5 (p = 0.016) and internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3) (FLT3-ITD) mutation (p = 0.048). Taking PTPN11 VAF 20% and 35.3% as the cutoff value, the patients were divided into two groups, and the overall survival and event-free survival (EFS) of the two groups were not significant. Multivariate analysis of Cox risk ratio model showed that white blood cell count and Eastern Cooperative Oncology Group (ECOG) physical status score were independent risk factors affecting the EFS. CONCLUSION: Our study observed that PTPN11 VAF may not be a prognostic factor in patients with PTPN11 AML. Newly diagnosed high white blood cell count and poor performance status were independent risk factors for EFS in PTPN11 AML.
PLP2 Could Be a Prognostic Biomarker and Potential Treatment Target in Glioblastoma Multiforme.
Qiao H, Li H
Pharmgenomics Pers Med · 2023 · PMID 37964785 · Full text
OBJECTIVE: This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM. METHODS: Utilizing the GEPIA2 and TCGA databases, we contra...
OBJECTIVE: This study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM. METHODS: Utilizing the GEPIA2 and TCGA databases, we contrasted the expression levels of PLP2 in GBM against normal tissue. We utilized GEPIA2 and LinkedOmics for survival analysis, recognized genes co-expressed with PLP2 via cBioPortal and GEPIA2, and implemented GO and KEGG analyses. The STRING database facilitated the construction of protein-protein interaction networks. We evaluated the relationship of PLP2 with tumor immune infiltrates using ssGSEA and the TIMER 2.0 database. An IHC assay assessed PLP2 and PDL-1 expression in GBM tissue, and the Drugbank database aided in identifying potential PLP2-targeting compounds. Molecular docking was accomplished using Autodock Vina 1.2.2. RESULTS: PLP2 expression was markedly higher in GBM tissues in comparison to normal tissues. High PLP2 expression correlated with a decrease in overall survival across two databases. Functional analyses highlighted a focus of PLP2 functions within leukocyte. Discrepancies in PLP2 expression were evident in immune infiltration, impacting CD4+ T cells, neutrophils, myeloid dendritic cells, and macrophages. There was a concomitant increase in PLP2 and PD-L1 expression in GBM tissues, revealing a link between the two. Molecular docking with ethosuximide and praziquantel yielded scores of -7.441 and -4.295 kcal/mol, correspondingly. CONCLUSION: PLP2's upregulation in GBM may adversely influence the lifespan of GBM patients. The involvement of PLP2 in pathways linked to leukocyte function is suggested. The positive correlation between PLP2 and PD-L1 could provide insights into PLP2's role in glioma modulation. Our research hints at PLP2's potential as a therapeutic target for GBM, with ethosuximide and praziquantel emerging as potential treatment candidates, especially emphasizing the potential of these compounds in GBM treatment targeting PLP2.
Personalized Approaches to Antiplatelet Treatment for Cardiovascular Diseases: An Umbrella Review.
Oliva A, Cao D, Spirito A … +5 more , Nicolas J, Pileggi B, Kamaleldin K, Vogel B, Mehran R
Pharmgenomics Pers Med · 2023 · PMID 37941790 · Full text
Antiplatelet therapy is the cornerstone of antithrombotic prevention in patients with established atherosclerosis, since it has been proven to reduce coronary, cerebrovascular, and peripheral thrombotic events. However,...
Antiplatelet therapy is the cornerstone of antithrombotic prevention in patients with established atherosclerosis, since it has been proven to reduce coronary, cerebrovascular, and peripheral thrombotic events. However, the protective effect of antiplatelet agents is counterbalanced by an increase of bleeding events that impacts on patients' mortality and morbidity. Over the last years, great efforts have been made toward personalized antithrombotic strategies according to the individual bleeding and ischemic risk profile, aiming to maximizing the net clinical benefit. The development of risk scores, consensus definitions, and the new promising artificial intelligence tools, as well as the assessment of platelet responsiveness using platelet function and genetic testing, are now part of an integrated approach to tailored antithrombotic management. Moreover, novel strategies are available including dual antiplatelet therapy intensity and length modulation in patients undergoing myocardial revascularization, the use of P2Y inhibitor monotherapy for long-term secondary prevention, the implementation of parenteral antiplatelet agents in high-ischemic risk clinical settings, and combination of antiplatelet agents with low-dose factor Xa inhibitors (dual pathway inhibition) in patients suffering from polyvascular disease. This review summarizes the currently available evidence and provides an overview of the principal risk-stratification tools and antiplatelet strategies to inform treatment decisions in patients with cardiovascular disease.
Hepatic Artery Infusion Chemotherapy Sequential Hepatic Artery Embolization Combined with Operation in the Treatment of Recurrent Massive Hepatocellular Carcinoma Achieved Pathological Complete Response: A Case Report.
Chen J, Liao X, Wu Y … +8 more , Ou S, Qin W, Yang C, Tan Y, Lao Q, Peng M, Peng T, Ye X
Pharmgenomics Pers Med · 2023 · PMID 37933333 · Full text
Hepatocellular carcinoma (HCC) recurrence, which encompasses both true recurrence resulting from cancer spread and de novo tumors developing within the same cancer-prone liver, presents a complication in approximately 70...
Hepatocellular carcinoma (HCC) recurrence, which encompasses both true recurrence resulting from cancer spread and de novo tumors developing within the same cancer-prone liver, presents a complication in approximately 70% of cases within a 5-year timeframe. The efficacy of neoadjuvant therapy for recurrence after hepatectomy for hepatocellular carcinoma is still unclear. We report a case of recurrent massive advanced hepatocellular carcinoma with pathological complete remission was treated by continuous hepatic arterial infusion chemotherapy (HAIC) and sequential transcatheter arterial embolization (TAE) combined with secondary operation. One month after resection, the patient recurred (massive type 141mm×76mm). After 4 times of HAIC sequential TAE conversion therapy, the tumor shrank significantly (70mm×29mm), alpha-fetoprotein(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels decreased significantly, residual liver volume[left half liver accounted for 39.85% of standard liver volume(left half liver + right anterior lobe) accounted for 80.17% of standard liver volume] and Indocyanine green 15-minute retention(ICG R15 8.0%) complies with surgical requirement.The second operation was performed, and the tumor was completely resected after hepatic blood flow occlusion Requirement. The postoperative pathological results showed complete remission (PCR) of the tumor, and no recurrence was found during the follow-up of 16 months. In this case, HAIC sequential TAE conversion therapy has good short-term effect on patients with postoperative recurrence of hepatocellular carcinoma, tumor burden is significantly reduced, the second surgery pathology achieves complete remission, safety and tolerance, it is worthy of study and promotion.
rs217727 of lncRNA H19 is Associated with Cervical Cancer Risk in the Chinese Han Population.
Dai J, Zhang S, Shi Y … +6 more , Xu J, Liu W, Yang J, Shi L, Yan Z, Li C
Pharmgenomics Pers Med · 2023 · PMID 37928407 · Full text
BACKGROUND: Long noncoding RNAs (LncRNAs) have been revealed to involve in cervical cancer (CC) developing. The current study was designed to explore the association of SNPs (rs217727, rs2366152, rs1859168, rs10505477) l...
BACKGROUND: Long noncoding RNAs (LncRNAs) have been revealed to involve in cervical cancer (CC) developing. The current study was designed to explore the association of SNPs (rs217727, rs2366152, rs1859168, rs10505477) located in the lncRNA H19, HOTAIR, HOTTIP and CASC8 genes with the risk of CC in a Chinese Han population. METHODS: Four SNPs were selected and genotyped in 1426 participants (274 CIN patients, 448 CC patients, and 704 healthy control individuals) using MassArray. The association of these SNPs with susceptibility to CC was evaluated. RESULTS: Significant differences in allelic distribution of rs217727 were observed in the comparison of CC with control ( = 0.001), indicating the risk of rs217727-A allele in CC (OR = 1.33; 95% CI: 1.12-1.58). The inheritance model analysis revealed that 2AA+GA genotype represented a certain risk of CC ( = 0.001, OR = 1.35; 95% CI: 1.13-1.62). The stratified analysis revealed a risk of the rs217727-A allele for cervical squamous cell carcinoma (SCC) ( = 0.002, OR = 1.33; 95% CI: 1.11-1.60). CONCLUSION: rs217727 in lncRNA H19 exhibited a significant correlation with CC susceptibility, particularly SCC, and A/A genotype of this SNP might present as a risk in CC.
Association Between Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density.
Yuan H, Wang C, Liu L … +3 more , Wang C, Zhang Z, Qu S
Pharmgenomics Pers Med · 2023 · PMID 37920752 · Full text
PURPOSE: The aim of this study was to explore the association between polymorphisms and the response to alendronate treatment in postmenopausal Chinese women with low bone mineral density. PATIENTS AND METHODS: In this...
PURPOSE: The aim of this study was to explore the association between polymorphisms and the response to alendronate treatment in postmenopausal Chinese women with low bone mineral density. PATIENTS AND METHODS: In this study, 460 postmenopausal women from Shanghai were included. All of them were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for a year. Four tag single nucleotide polymorphisms (SNPs) in gene were genotyped. Bone mineral densities of lumbar spine (L1-L4), femoral neck and total hip were measured at baseline and after 12 months of treatment, respectively. RESULTS: After 1-year of treatment, there was no significant differences in BMI between baseline and follow-up. After alendronate treatment, the BMD of L1-4, femoral neck and total hip all increased significantly (all < 0.001), with average increases of 4.33 ± 6.42%, 1.85 ± 4.20%, and 2.36 ± 3.79%, respectively. There was no significant difference in BMD at L1-L4, the femoral neck and total hip between different genotype groups at baseline (>0.05). After 1-year treatment with alendronate, rs12746973 and rs10847 were associated with the % change of BMD at L1-L4 (=0.038) and % change of BMD at femoral neck (=0.038), respectively. Furthermore, rs10847 was associated with BMD response at femoral neck (=0.013). However, the associations were not significant after Bonferroni correction. CONCLUSION: We concluded that the common variations of gene were potentially associated with the therapeutic response to alendronate treatment in Chinese women with low bone mineral density. However, further validation is needed.
A Case Report of Cardiofaciocutaneous Syndrome with MAP2K1 Pathogenic Variant [Letter].
Furqoni AH, Fajarwati I, Poetranto AL
Pharmgenomics Pers Med · 2023 · PMID 37904875 · Full text
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Microarray Expression Profile and Bioinformatic Analysis of Circular RNA in Human Arteriosclerosis Obliterans.
Zhou Y, Cai H, Huang L … +6 more , Wang M, Liu R, Wang S, Qin Y, Yao C, Hu Z
Pharmgenomics Pers Med · 2023 · PMID 37899885 · Full text
BACKGROUND: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer...
BACKGROUND: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct. METHODS AND RESULTS: This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group ( < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO. CONCLUSION: This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.
Influence of CYP450 Enzymes and ABCB1 Polymorphisms on Clopidogrel Response in Moroccan Patients with Acute Coronary Syndromes.
Mouhrach I, Bouguenouch L, Kamal A … +5 more , Meriame A, El Khorb N, El Azami El Idrissi M, Akoudad H, Bekkari H
Pharmgenomics Pers Med · 2023 · PMID 37810546 · Full text
INTRODUCTION: Clopidogrel is an antiplatelet prodrug primarily prescribed to prevent or treat acute coronary syndrome (ACS) or acute ischemic stroke (IS), polymorphisms of genes encoding cytochrome P-450 (CYP) and P-glyc...
INTRODUCTION: Clopidogrel is an antiplatelet prodrug primarily prescribed to prevent or treat acute coronary syndrome (ACS) or acute ischemic stroke (IS), polymorphisms of genes encoding cytochrome P-450 (CYP) and P-glycoprotein transporter, could affect the efficiency of clopidogrel absorption and biotransformation, especially during the first critical hours following its administration. METHODS: The present study was designed to investigate the potential association of clopidogrel responsiveness and 14 polymorphisms in the genes encoding the CYPs (CYP2C9, 2C19, 3A4, 3A5, 1A2, and 2B6), the ATP binding cassette subfamily B member 1 (ABCB1). Platelet aggregation activity was measured after 8h of 300mg clopidogrel administration for fifty-five ACS patients. RESULTS: There was no significant association between polymorphism of the studied CYPs and clopidogrel responsiveness (P>0.05). The frequency of the ABCB1 3435 T allele in clopidogrel non-responders was higher (78.9%) compared to responders (52.8%), but this difference was not significant (P=0.057). Demographic characteristics, comorbidities, concomitant treatments were not associated with clopidogrel response. DISCUSSION: There was no effect of the studied genetic variations and demographic factors on the platelet activity of clopidogrel in Moroccan ACS patients.
Homocysteine Reduction for Stroke Prevention: Regarding the Recent AHA/ASA 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.
Brown C, Wang J, Jiang H … +1 more , Elias MF
Pharmgenomics Pers Med · 2023 · PMID 37810545 · Full text
Reduction of secondary ischemic stroke risk following an initial stroke is an important goal. The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack assembles opportunities for up to 80% seco...
Reduction of secondary ischemic stroke risk following an initial stroke is an important goal. The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack assembles opportunities for up to 80% secondary stroke reduction. Homocysteine reduction was not included in the recommendations. The reduction of homocysteine with low doses of folic acid has been shown to reduce ischemic stroke and all stroke. This has been obscured by studies using high doses of folic acid and cyanocobalamin in patients with renal failure and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. The confounding impacts of high dose folic acid and cyanocobalamin toxicity in renal failure and MTHFR C677T subgroups are discussed. New studies show that their toxicity is due to non-bioequivalence to the natural dietary forms, L-methylfolate and methylcobalamin. Low doses of folic acid and cyanocobalamin are safer than high doses for these subpopulations. Even lower toxicity with greater effectiveness for reducing homocysteine is seen with L-methylfolate and methylcobalamin, which are safe at high doses. Retinal vascular imaging is a noninvasive method for evaluating central nervous system (CNS) microangiopathy. A formulation containing l-methylfolate and methylcobalamin has been shown to reduce homocysteine and increase perfusion in diabetic retinopathy. This supports homocysteine intervention for CNS ischemia. Future ischemic stroke intervention studies could benefit from monitoring retinal perfusion to estimate the impact of risk reduction strategies. The omission of a recommendation for homocysteine and secondary stroke reduction through the use of B vitamins should be reconsidered in light of re-analysis of major B vitamin intervention studies and new technologies for monitoring CNS perfusion. We recommend revision of the 2021 Guideline to include homocysteine reduction with low doses of folic acid and cyanocobalamin, or better yet, L-methylfolate and methylcobalamin, making a good clinical guideline better.
Novel Mutations in Indian Population with Cardiomyopathies.
Rani DS, Kasala A, Dhandapany PS … +5 more , Muthusami U, Kunnoth S, Rathinavel A, Ayapati DR, Thangaraj K
Pharmgenomics Pers Med · 2023 · PMID 37750083 · Full text
BACKGROUND: Mutations in Myosin Binding Protein C () are one of the most frequent causes of cardiomyopathies in the world, but not much data are available in India. METHODS: We carried out targeted direct sequencing of i...
BACKGROUND: Mutations in Myosin Binding Protein C () are one of the most frequent causes of cardiomyopathies in the world, but not much data are available in India. METHODS: We carried out targeted direct sequencing of in 115 hypertrophic (HCM) and 127 dilated (DCM) cardiomyopathies against 197 ethnically matched healthy controls from India. RESULTS: We detected 34 single nucleotide variations in , of which 19 were novel. We found a splice site mutation [(IVS6+2T) T>G] and 16 missense mutations in Indian cardiomyopathies [5 in HCM; E258K, T262S, H287L, R408M, V483A: 4 in DCM; T146N, V321L, A392T, E393K and 7 in both HCM and DCM; L104M, V158M, S236G, R272C, T290A, G522E, A626V], but those were absent in 197 normal healthy controls. Interestingly, we found 7 out of 16 missense mutations (V158M, E258K, R272C, A392T, V483A, G522E, and A626V) in were altering the evolutionarily conserved native amino acids, accounted for 8.7% and 6.3% in HCM and DCM, respectively. The bioinformatic tools predicted that those 7 missense mutations were pathogenic. Moreover, the co-segregation of those 7 mutations in families further confirmed their pathogenicity. Remarkably, we also identified compound mutations within the gene of 6 cardiomyopathy patients (5%) with more severe disease phenotype; of which, 3 were HCM (2.6%) [(1. K244K + E258K + (IVS6+2T) T>G); (2. L104M + G522E + A626V); (3. P186P + G522E + A626V]; and 3 were DCM (2.4%) [(1. 5'UTR + A392T; 2. V158M+G522E; and 3.V158M + T262T + A626V]. CONCLUSION: The present comprehensive study on has revealed both single and compound mutations in and their association with disease in Indian Population with Cardiomyopathies. Our findings may perhaps help in initiating diagnostic strategies and eventually recognizing the targets for therapeutic interventions.
Genome-Wide Identification of lncRNA and mRNA for Diagnosing Type 2 Diabetes in Saudi Arabia.
Albogami S
Pharmgenomics Pers Med · 2023 · PMID 37731406 · Full text
PURPOSE: According to the World Health Organization, Saudi Arabia ranks seventh worldwide in the number of patients with diabetes mellitus. To our knowledge, no research has addressed the potential of noncoding RNA as a...
PURPOSE: According to the World Health Organization, Saudi Arabia ranks seventh worldwide in the number of patients with diabetes mellitus. To our knowledge, no research has addressed the potential of noncoding RNA as a diagnostic and/or management biomarker for patients with type 2 diabetes mellitus (T2DM) living in high-altitude areas. This study aimed to identify molecular biomarkers influencing patients with T2DM living in high-altitude areas by analyzing lncRNA and mRNA. PATIENTS AND METHODS: RNA sequencing and bioinformatics analyses were used to identify significantly expressed lncRNAs and mRNAs in T2DM and healthy control groups. Coding potential was analyzed using coding-noncoding indices, the coding potential calculator, and PFAM, and the lncRNA function was predicted using Pearson's correlation. Differentially expressed transcripts between the groups were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify the biological functions of both lncRNAs and mRNAs. RESULTS: We assembled 1766 lncRNAs in the T2DM group, of which 582 were novel. This study identified three lncRNA target genes (, and ) and seven mRNAs (, and ) significantly enriched in important pathways, playing a role in the progression of T2DM. CONCLUSION: To the best of our knowledge, this comprehensive study is the first to explore the applicability of certain lncRNAs as diagnostic or management biomarkers for T2DM in females in Taif City, Saudi Arabia through the genome-wide identification of lncRNA and mRNA profiling using RNA seq and bioinformatics analysis. Our findings could help in the early diagnosis of T2DM and in designing effective therapeutic targets.
Clinical Significance of NAT2 Genetic Variations in Type II Diabetes Mellitus and Lipid Regulation.
Jarrar Y, Abudahab S, Abdul-Wahab G … +7 more , Zaiter D, Madani A, Abaalkhail SJ, Abulebdah D, Alhawari H, Musleh R, Lee SJ
Pharmgenomics Pers Med · 2023 · PMID 37724295 · Full text
BACKGROUND: N-acetyltransferase 2 (NAT2) enzyme is a Phase II drug-metabolizing enzyme that metabolizes different compounds. Genetic variations in can influence the enzyme's activity and potentially lead to the developm...
BACKGROUND: N-acetyltransferase 2 (NAT2) enzyme is a Phase II drug-metabolizing enzyme that metabolizes different compounds. Genetic variations in can influence the enzyme's activity and potentially lead to the development of certain diseases. AIM: This study aimed to investigate the association of variants with the risk of Type II diabetes mellitus (T2DM) and the lipid profile among Jordanian patients. METHODS: We sequenced the whole protein-coding region in using Sanger's method among a sample of 45 Jordanian T2DM patients and 50 control subjects. Moreover, we analyzed the lipid profiles of the patients and examined any potential associations with variants. RESULTS: This study revealed that the heterozygous genotype is significantly ( = 0.03) more common among T2DM (44%) than non-T2DM subjects (23.5%). Furthermore, the frequency of homozygous genotype was found to be significantly higher ( = 0.03) among T2DM patients (26.7%) compared to that of non-T2DM subjects (11%). The heterozygous genotype was exclusively observed in T2DM patients (11.1%) and absent in the control non-T2DM group. Moreover, among T2DM patients, those with a homozygous T/T genotype exhibited significantly higher levels of triglycerides (381.50 ± 9.19 ng/dL) with a value of 0.01 compared to those with heterozygous C/T (136.23 ± 51.12 ng/dL) or wild-type C/C (193.65 ± 109.89 ng/dL) genotypes. T2DM patients with homozygous G/G genotype had a significantly ( = 0.04) higher triglyceride levels (275.67 ± 183.42 ng/dL) than the heterozygous (140.02 ± 49.53 ng/dL) and the wild (193.65 ± 109.89 ng/dL). CONCLUSION: The finding in this study suggests that the gene is a potential biomarker for the development of T2DM and changes in triglyceride levels among Jordanians. However, it is important to note that our sample size was limited; therefore, further clinical studies with a larger cohort are necessary to validate these findings.
Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer.
He H, Ma H, Chen Z … +4 more , Chen J, Wu D, Lv X, Zhu J
Pharmgenomics Pers Med · 2023 · PMID 37724294 · Full text
PURPOSE: Chromosomal abnormalities represent genomic signatures linked to cancer prognosis and responses to chemotherapy, immunotherapy, and drug resistance. This study aimed to investigate the impact of chromosome copy...
PURPOSE: Chromosomal abnormalities represent genomic signatures linked to cancer prognosis and responses to chemotherapy, immunotherapy, and drug resistance. This study aimed to investigate the impact of chromosome copy number variants (CNVs) on the efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC) patients, as well as its prognostic implications for progression-free survival (PFS) and overall survival (OS) in EGFR wild-type patients. METHODS: A total of 110 patients with advanced NSCLC were enrolled in this study and categorized into EGFR-mutated and wild-type groups. Utilizing next-generation sequencing (NGS) technology, we assessed 24 genes and chromosome CNVs associated with lung cancer pathways in patients' tissue samples. RESULTS: Within the EGFR-mutated group, patients with a gain in Chr 1p13.3-p13.1 exhibited poor TKI responses, a high relapse rate, and shortened PFS ( = 0.002). Conversely, EGFR-mutated patients with a gain in 14q31.1-q31.3 demonstrated favorable TKI responses and relatively extended PFS ( = 0.005). Among EGFR wild-type patients, the presence of 7q31.1-q31.31 CNV emerged as an independent factor influencing both PFS and OS ( = 0.013, = 0.004). Notably, patients with a gain in 7q31.1-q31.31 exhibited prolonged PFS and OS. Additionally, independent prognostic significance for OS in EGFR wild-type patients was observed for CNVs in 9q21.31-q22.2 and 11p11.11-q12.1 regions ( = 0.001). Patients with gains in these regions experienced extended OS, while losses were predictive of poorer outcomes. CONCLUSION: Our results suggested that chromosomal copy number variation is a practical indicator for predicting the response of EGFR-targeted therapy and prognosis for NSCLC patients.
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