Pharmacogenomics And Personalized Medicine[JOURNAL]
Sun
200 papers
GABRP is a Promising Prognostic Biomarker and Associated with Immune Cell Infiltration in Lung Squamous Cell Carcinoma.
Fu J, Lin J, Zeng X … +3 more , Li G, Wei Y, Xian L
Pharmgenomics Pers Med · 2023 · PMID 37091829 · Full text
BACKGROUND: GABRP has been reported to play an oncogenic role in various carcinomas. However, no report has been found for its involvement in lung squamous cell carcinoma (LUSC) development yet. We aimed to explore the e...
BACKGROUND: GABRP has been reported to play an oncogenic role in various carcinomas. However, no report has been found for its involvement in lung squamous cell carcinoma (LUSC) development yet. We aimed to explore the expression and prognostic roles of GABRP and assessment of its association with tumor microenvironment in LUSC. METHODS: The GABRP expression in LUSC was analyzed using TCGA, GEO, and HPA databases. The Kaplan-Meier, Cox regression analysis, and receiver operating characteristic (ROC) curve were applied to assess the prognostic and diagnostic values of GABRP in LUSC. We also performed ESTIMATE and ssGSEA to explore the association between GABRP expression and immune cell infiltrations. GABRP was highly expressed in LUSC patients, and up-regulation of GABRP was associated with shorter overall survival (OS). Cox regression analysis indicated that GABRP was an independent prognostic factor for LUSC patients. KEGG analysis revealed that GABRP may play an important role in starch and sucrose metabolism and nicotine addiction. Specifically, GABRP expression showed significant positive correlations with the infiltration levels of most types of immune cells, as well as immune checkpoint molecules expression. CONCLUSION: Up-regulation of GABRP in LUSC could be severed as a prognostic marker and a potential target for immunotherapy in LUSC.
Case Report: Congenital Myasthenic Syndrome Presenting with Bilateral Vocal Cord Paralysis Caused by De-Novel Compound Heterozygous MUSK Mutation.
Jiang L, Wang SC, Zhang J … +3 more , Han FG, Zhao J, Xu Y
Pharmgenomics Pers Med · 2023 · PMID 37091828 · Full text
BACKGROUND: We report the genetic etiology of a case of bilateral vocal cord paralysis in a female infant. CASE DESCRIPTION: The female infant developed dyspnea after birth, which improved with treatment, allowing her to...
BACKGROUND: We report the genetic etiology of a case of bilateral vocal cord paralysis in a female infant. CASE DESCRIPTION: The female infant developed dyspnea after birth, which improved with treatment, allowing her to be discharged from the local hospital. At 2 months of age, the child experienced a recurrence of dyspnea and was treated in a local hospital with interventions such as tracheal intubation and mechanical ventilation. However, as the child continued to suffer from dyspnea, she was transferred to the neonatal intensive care unit of the Children's Hospital affiliated to Zhengzhou University for further treatment. A second electronic nasopharyngoscopy examination revealed bilateral vocal cord paralysis. The child underwent a tracheostomy due to a failure to wean from mechanical ventilation; after surgery, the respirator was effectively removed, and oxygen delivery ceased. The child and her parents underwent genetic testing with next-generation sequencing technology, which revealed that the child had two heterozygous variants in the MUSK gene, namely the c.2287G>A heterozygous mutation (p.Ala763Thr) and the c.790C>T heterozygous mutation. In addition, Sanger sequencing was performed, which confirmed that these two mutations were, respectively, inherited from the mother and father. CONCLUSION: Congenital myasthenic syndrome caused by MUSK gene mutations can present clinically as bilateral vocal cord paralysis in neonates.
May Be a Potential Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma.
Lan C, Huang X, Liao X … +7 more , Zhou X, Peng K, Wei Y, Han C, Peng T, Wang J, Zhu G
Pharmgenomics Pers Med · 2023 · PMID 37091827 · Full text
OBJECTIVE: The mechanisms of pseudouridine synthase (PUS) are not definite in hepatocellular carcinoma (HCC), the objective of this study is to investigate the effect of PUS genes in HCC. MATERIALS AND METHODS: Different...
OBJECTIVE: The mechanisms of pseudouridine synthase (PUS) are not definite in hepatocellular carcinoma (HCC), the objective of this study is to investigate the effect of PUS genes in HCC. MATERIALS AND METHODS: Differentially expressed and prognostic gene of PUS enzymes was identified based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. For the identified gene, pseudouridine synthase 1 (), was used for further research. The clinicopathological feature of was analyzed by Student's -test. Prognostic significance was explored by Kaplan-Meier (KM) analysis and Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve was applied to appraise diagnostic and prognostic value. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were implemented to explore mechanism of . A Guangxi cohort was applied to verify differential expression. In vitro cell experiments were implemented to investigate the influence for proliferation, reactive oxygen species (ROS) level, migration, and invasion of HCC cells after a knockdown of . RESULTS: was significantly overexpressed in HCC tissues, and patients with high were related to unpromising clinicopathological features. Survival analysis revealed high expression was associated with a poor overall survival (OS) and 1 year-recurrence free survival (RFS), was an independent risk factor. Meanwhile, ROC curve showed that had a diagnostic and prognostic significance to HCC. Functional enrichment analysis implied that may be involved in metabolic pathways, mitochondrial function, non-alcoholic fatty liver disease (NAFLD), and some important carcinogenic pathways. Cell assays revealed that knockdown of significantly constrained the migration, proliferation, invasion and improved the ROS level of HCC cells. CONCLUSION: may be a prognostic biomarker and a underlying treatment target for HCC.
Gene Polymorphisms Increase the Susceptibility to Tuberculosis.
Lu T, Wang M, Liu N … +7 more , Zhang S, Shi L, Bao L, Luo F, Shi L, Liu S, Yao Y
Pharmgenomics Pers Med · 2023 · PMID 37077653 · Full text
PURPOSE: Tuberculosis (TB) is known to result from a complex interaction between the host immune response and infection. The transporter associated with antigen processing (TAP) plays an important role in the processing...
PURPOSE: Tuberculosis (TB) is known to result from a complex interaction between the host immune response and infection. The transporter associated with antigen processing (TAP) plays an important role in the processing and presentation pathways for the () antigen. To investigate the possible association of the and genes with TB. PATIENTS AND METHODS: A total of 449 TB patients and 435 control subjects were included in this study, and single nucleotide polymorphisms (SNPs) in the gene, as well as and alleles, were genotyped. RESULTS: gene association analysis of TB diseases showed that rs41551515-T in the gene was significantly associated with susceptibility to TB (=7.96E-04, OR=4.124, 95% CI: 1.683-10.102), especially pulmonary TB (PTB, =6.84E-04, OR=4.350, 95% CI: 1.727-10.945), and the combination of rs1057141-T-rs1135216-C in the gene significantly increased the risk of TB susceptibility (=5.51E-05, OR=10.899, 95% CI: 2.555-46.493). Five novel alleles were detected in Yunnan Han people, and the allele frequency of (rs41555220-rs41549617-rs1057141-rs1135216-rs1057149-rs41551515: C-A-T-C-C-T) was notably increased in all TB patients, including in the PTB and EPTB subgroups, and was significantly associated with the risk of susceptibility to TB. However, no association between the gene and TB was found in this study. CONCLUSION: Host genetic variants of rs41551515-T and the combination rs1057141-T-rs1135216-C, as well as may play a critical role in susceptibility to TB disease.
miR-139-5p and miR-451a as a Diagnostic Biomarker in LUSC.
Gao B, Li R, Song X … +2 more , Hu S, Yang F
Pharmgenomics Pers Med · 2023 · PMID 37063774 · Full text
BACKGROUND: Lung squamous cell carcinoma (LUSC) is a type of lung cancer that originates from segmental or subsegmental bronchial mucosa. There is evidence that miRNA plays an important role in the occurrence and progres...
BACKGROUND: Lung squamous cell carcinoma (LUSC) is a type of lung cancer that originates from segmental or subsegmental bronchial mucosa. There is evidence that miRNA plays an important role in the occurrence and progression of tumors. METHODS: In this study, plasma samples of patients with early LUSC and healthy volunteers were subjected to miRNA sequencing, and the levels of differentially expressed miRNAs (DEMs) in LUSC tissues were analyzed using R language. Cox regression and Kaplan-Meier (K-M) survival curve analyses were performed to determine the relationship between DEMs and prognosis in LUSC, and PCR method was verified for the plasma expression level of DEMs in patients with LUSC. The levels of CYFRA21-1 and SCC-Ag in plasma were measured, and area under curve (AUC) was used to evaluate the diagnostic value of the DEMs. RESULTS: A total of 21 DEMs were screened out by sequencing. The expression levels of DEMs in tissue samples in the TCGA database were analyzed, and four DEMs with consistent expression levels were further screened from plasma and tissue samples. Regression analysis and K-M curve were performed to select two DEMs (miR-139-5p, miR-451a) that were correlated with the prognosis. PCR verification results showed that the levels of miR-451a and miR-139-5p were low in patients, and the level of miR-139-5p in late stages III & IV with the patients of LUSC was higher than that in stages I & II. The AUC values of the four indicators (SCC-Ag, CYFRA21-1, miR-451a and miR-139-5p) in the diagnosis of LUSC, early and late cases were 0.884, 0.935 and 0.778, respectively. CONCLUSION: The detection of miR-139-5p and miR-451a levels in plasma has a certain potential in the non-invasive diagnosis, especially in patients with early stages of LUSC.
Apolipoprotein E Gene Polymorphism Effects on Lipid Metabolism and Risk of Cerebral Infarction in Northwest Han Chinese Population.
Wang Y, Yang S, Zhang S … +2 more , Lu X, Ma W
Pharmgenomics Pers Med · 2023 · PMID 37051559 · Full text
BACKGROUND: The apolipoprotein E (ApoE) genetic variation may contribute to the development of Cerebral Infarction (CI). Serum lipid levels are known risk factors for CI, but the effect of the ApoE gene polymorphism on l...
BACKGROUND: The apolipoprotein E (ApoE) genetic variation may contribute to the development of Cerebral Infarction (CI). Serum lipid levels are known risk factors for CI, but the effect of the ApoE gene polymorphism on lipid metabolism remains unclear. This retrospective cohort study was designed to determine the role of ApoE genotypes in CI risk and the relationships between ApoE gene polymorphism and serum lipid levels among the population of northwest China. PATIENTS AND METHODS: 517 CI patients and 517 non-CI controls were enrolled in the study. Polymerase chain reaction and hybridization were utilized to determine the ApoE gene polymorphisms. RESULTS: The ε3/ε4 genotype and ε4 allele frequency were significantly higher in CI patients than in controls. When stratified by age and sex, statistically significant differences in the distribution and frequency of the ε3/ε4 genotype and ε4 allele were found between patients and controls. Compared to ε2 carriers, ε4 carriers had significantly lower ApoE levels and higher low-density lipoprotein cholesterol (LDL-C), ApoB and ApoB/ApoA-I levels in both two groups. Additionally, control participants with ε4 carriers had significantly higher levels of lipoprotein and total cholesterol (TC) levels than ε2 carriers, while CI patients with ε4 carriers had a significantly lower level of ApoA-I. After adjusting for other established risk factors, drinking, hypertension, lipoprotein, triglycerides (TG) and ε4 allele were significant independent risk factors for CI, which was shown to be associated with a nearly two-fold CI risk. CONCLUSION: This study demonstrated that ε4 allele is independent risk factors for CI among patients in Northwest China. ApoE polymorphism was associated with CI, which was partly mediated through blood lipids and may also be mediated through non-lipid pathways. These data might be of great clinical significance in individualized preventive and therapeutic strategies.
Construction and Validation of a Novel Nomogram for Predicting the Recurrence of Diffuse Large B Cell Lymphoma Treated with R-CHOP.
Gong Y, Yan H, Yang Y … +3 more , Zhai B, Huang Z, Zhang Z
Pharmgenomics Pers Med · 2023 · PMID 37035544 · Full text
PURPOSE: To explore recurrence-risk factors of diffuse large B cell lymphoma (DLBCL) and construct a risk nomogram for predicting recurrence. PATIENTS AND METHODS: A retrospective analysis was performed on 228 DLBCL pati...
PURPOSE: To explore recurrence-risk factors of diffuse large B cell lymphoma (DLBCL) and construct a risk nomogram for predicting recurrence. PATIENTS AND METHODS: A retrospective analysis was performed on 228 DLBCL patients who achieved complete remission after R-CHOP treatment between January 2015 and December 2019. Univariate and multivariate analyses were applied to identify recurrence-related risk factors from the pretreatment evaluation factors covering patients' demographic characteristics, clinical manifestations, serological indicators, pathological and immunohistochemical results. A nomogram was developed based on the above results and validated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the calibration curve. RESULTS: The training and validation cohorts consisted of 160 and 68 patients (randomized by 7:3). Of the whole cohort, 50 of 228 (21.9%) cases recurred during follow-up. Three recurrence-risk factors including BCL2 expression (P = 0.027), CD10 expression (P = 0.021), LDH level (P = 0.004) were identified from multivariate analysis and entered the final nomogram. The C-index of the nomogram was 0.815 in training cohort and 0.797 in the validation cohort, higher than that of IPI system (0.699) and NCCN-IPI system (0.709). And the 1-year, 2-year, 3-year, and 4-year areas under ROC (AUC) were 0.812, 0.850, 0.837, and 0.801, respectively. The calibration curves also showed a good discrimination capability and accuracy. CONCLUSION: The novel nomogram incorporating the three independent risk factors (BCL2 expression, CD10 expression and LDH level) provided a valuable tool for predicting DLBCL recurrence.
Use of Continuous Glucose Monitors to Manage Type 1 Diabetes Mellitus: Progress, Challenges, and Recommendations.
Friedman JG, Cardona Matos Z, Szmuilowicz ED … +1 more , Aleppo G
Pharmgenomics Pers Med · 2023 · PMID 37025558 · Full text
Type 1 diabetes (T1D) management has been revolutionized with the development and routine utilization of continuous glucose monitoring (CGM). CGM technology has allowed for the ability to track dynamic glycemic fluctuati...
Type 1 diabetes (T1D) management has been revolutionized with the development and routine utilization of continuous glucose monitoring (CGM). CGM technology has allowed for the ability to track dynamic glycemic fluctuations and trends over time allowing for optimization of medical therapy and the prevention of dangerous hypoglycemic events. This review details currently-available real-time and intermittently-scanned CGM devices, clinical benefits, and challenges of CGM use, and current guidelines supporting its use in the clinical care of patients with T1D. We additionally describe future issues that will need to be addressed as CGM technology continues to evolve.
Rs11479 in Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.
Jia X, Zhang T, Sun J … +8 more , Lin H, Bai T, Qiao Y, Li Y, Li G, Li G, Peng X, Zhang A
Pharmgenomics Pers Med · 2023 · PMID 37025557 · Full text
OBJECTIVE: gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between polymorphi...
OBJECTIVE: gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. METHODS: A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of polymorphism and mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of according to genotype status was analyzed using non-parameter test. RESULTS: Prevalence of rs11479 in among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, =0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of than that of patients with GG genotype (<0.001). CONCLUSION: Polymorphism rs11479 in gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of . The conclusion of this study should be validated in prospective clinical trials subsequently.
RUNX2 Reverses p53-Induced Chemotherapy Resistance in Gastric Cancer.
Huang Y, Liang L, Zhao YX … +4 more , Yao BH, Zhang RM, Song L, Zhang ZT
Pharmgenomics Pers Med · 2023 · PMID 37009416 · Full text
OBJECTIVE: Gastric cancer is one of the most common malignancies worldwide; however, its overall mortality has not improved significantly over the last decade. Chemoresistance plays a critical role in this issue. This st...
OBJECTIVE: Gastric cancer is one of the most common malignancies worldwide; however, its overall mortality has not improved significantly over the last decade. Chemoresistance plays a critical role in this issue. This study aimed to clarify the role and mechanism of runt-related transcription factor 2 (RUNX2) in platinum-based chemotherapy resistance. METHODS: First, a drug-resistant model of gastric cancer cells was established to evaluate the relative expression level of the RUNX2 as a potential biomarker of chemotherapy resistance. Next, exogenous silencing was conducted to study whether RUNX2 could reverse drug resistance and understand the underlying mechanisms. Simultaneously, the correlation between the clinical outcomes of 40 patients after chemotherapy and the RUNX2 expression levels in tumor samples was analyzed. RESULTS: We discovered that RUNX2 was significantly expressed in drug-resistant gastric cancer cells and tissues; it was also reversibly resistant to transformation treatment by exogenous RUNX2 silencing. It is confirmed that RUNX2 negatively regulates the apoptosis pathway of the p53 to reduce the chemotherapeutic effects of gastric cancer. CONCLUSION: RUNX2 is a possible target for platinum-based chemotherapy resistance.
Current Understanding of Inherited Modifiers of FVIII Pharmacokinetic Variation.
Swystun LL, Lillicrap D
Pharmgenomics Pers Med · 2023 · PMID 36998673 · Full text
The inherited bleeding disorder hemophilia A involves the quantitative deficiency of the coagulation cofactor factor VIII (FVIII). Prophylactic treatment of severe hemophilia A patients with FVIII concentrates aims to re...
The inherited bleeding disorder hemophilia A involves the quantitative deficiency of the coagulation cofactor factor VIII (FVIII). Prophylactic treatment of severe hemophilia A patients with FVIII concentrates aims to reduce the frequency of spontaneous joint bleeding and requires personalized tailoring of dosing regimens to account for the substantial inter-individual variability of FVIII pharmacokinetics. The strong reproducibility of FVIII pharmacokinetic (PK) metrics between repeat analyses in the same individual suggests this trait is genetically regulated. While the influence of plasma von Willebrand factor antigen (VWF:Ag) levels, ABO blood group, and patient age on FVIII PK is well established, estimates suggest these factors account for less than 35% of the overall variability in FVIII PK. More recent studies have identified genetic determinants that modify FVIII clearance or half-life including gene variants that impair VWF-FVIII binding resulting in the accelerated clearance of VWF-free FVIII. Additionally, variants in receptors that regulate the clearance of FVIII or the VWF-FVIII complex have been associated with FVIII PK. The characterization of genetic modifiers of FVIII PK will provide mechanistic insight into a subject of clinical significance and support the development of personalized treatment plans for patients with hemophilia A.
The Allelic Expression of RNA Editing Gene in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.
Zeng J, Han L, Wang T … +5 more , Huang L, Zheng Y, Zhang N, Li Z, Yang M
Pharmgenomics Pers Med · 2023 · PMID 36970122 · Full text
INTRODUCTION: Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to th...
INTRODUCTION: Transarterial chemoembolization (TACE) is the commonly used therapy of unresectable hepatocellular carcinoma (HCC), though the prognosis of different TACE-treated HCC patients varies, which may be due to the heterogeneity of HCC tumors caused by genetic variants and epigenetic changes such as RNA editing. There is dysregulated RNA adenosine-to-inosine (A-to-I) editing in HCC and RNA-edited genes are involved in the epigenetic process. It remains unclear how genetic variants of RNA editing genes affect the prognosis of HCC cases treated by TACE. METHODS: In this study, we examined 28 potentially functional single-nucleotide polymorphisms (SNPs) of four RNA editing genes ( and ) in two independent TACE patient cohorts. RESULTS: We found that rs1051367 and rs2253763 polymorphisms were markedly associated with the prognosis of HCC cases who received TACE in both cohorts. In HCC cells, the rs2253763 C-to-T change in 3'-untranslated region attenuated its binding with miR-542-3p and allele-specifically elevated levels. Consistent with this, patients carrying the rs2253763 C allele showed reduced expression in cancer tissues and notably shorter survival after TACE therapy in comparison with individuals with the T allele. Ectopic profoundly enhanced the efficacy of oxaliplatin, one of the common TACE chemotherapeutic drugs. DISCUSSION: Our findings highlighted the value of polymorphisms as prognostic markers in TACE therapy for HCC patients. Notably, our findings revealed that targeting the ADARB1 enzyme may be a promising therapeutic strategy in combination with TACE for HCC cases.
Anlotinib Enhances the Therapeutic Effect of Bladder Cancer with GSDMB Expression: Analyzed from TCGA Bladder Cancer Database & Mouse Bladder Cancer Cell Line.
Wang C, Cao Q, Zhang S … +5 more , Liu H, Duan H, Xia W, Shen H, Wang C
Pharmgenomics Pers Med · 2023 · PMID 36960215 · Full text
INTRODUCTION AND OBJECTIVE: The mitogen-activated protein kinase (MAPK) pathway is inhibited by the pan-target inhibitor Anlotinib, which induces tumor cell death. In addition to the common apoptosis and necrosis, there...
INTRODUCTION AND OBJECTIVE: The mitogen-activated protein kinase (MAPK) pathway is inhibited by the pan-target inhibitor Anlotinib, which induces tumor cell death. In addition to the common apoptosis and necrosis, there is also a pyroptosis mode of cancer cell death in recent years, which is mainly manifested by the cleavage of gasdermin proteins (GSDMs). Gasdermin B (GSDMB) participates in the progression and outcome of bladder cancer. The efficacy and mechanism of Anlotinib in the treatment of GSDMB-positive bladder tumors have not been studied to date. METHODS: The relationship between GSDMB expression and tumor stage, overall survival rate, immunotherapy response, tumor recurrence and progression rate was analyzed from the TCGA bladder cancer database. Anlotinib was used to treat GSDMB-positive bladder cancer in mice followed by flow analysis of the secretion of inflammatory factors related to pyroptosis and the level of anti-tumor factors. Western blot analysis detected which MAPK and MEK signal transduction pathways. RESULTS: TCGA data analysis showed that the overall survival rate of bladder cancer patients with high GSDMB expression was better than that of patients with low GSDMB expression. In vivo experiments showed that Anlotinib was more effective in the treatment of GSDMB-positive bladder cancer than GSDMB-negative bladder cancer. Anlotinib can increase the secretion of antitumor-related factors in GSDMB-positive bladder cancer such as TNF-a and CD107a. In addition, Anlotinib also induced an increase in GSDMB protein expression. Anlotinib treatment of GSDMB-positive bladder cancer decreased AKT and MEK protein expression, which were involved in Anlotinib signal transduction pathway. CONCLUSION: Anlotinib has a strong antitumor effect on GSDMB-positive bladder tumors. This effect is mainly achieved by anlotinib stimulating the secretion of relevant antitumor factors by lymphocytes. The PI3K/AKT and MEK signal transduction pathways were inhibited by Anlotinib in bladder cancer expressing GSDMB protein.
Discovery of Drug-Responsive Phenomic Alteration-Related Driver Genes in the Treatment of Coronary Heart Disease.
Guan S, Yu YN, Li B … +7 more , Gu H, Chen L, Wang N, Wang B, Liu X, Liu J, Wang Z
Pharmgenomics Pers Med · 2023 · PMID 36945217 · Full text
BACKGROUND: The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing. METHODS: The phenomic alteration-related genes...
BACKGROUND: The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing. METHODS: The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using || > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint. RESULTS: A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression. CONCLUSION: Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.
Resistance to PARP Inhibitors After First-Line Platinum-Based Chemotherapy in a Patient with Advanced Ovarian Cancer with a Pathogenic Somatic BRCA1 Mutation.
Zhong L, Yin R, Song L
Pharmgenomics Pers Med · 2023 · PMID 36942084 · Full text
PARP inhibitors (PARPi) are the maintenance therapy after first line platinum-based chemotherapy for patients with advanced epithelial ovarian cancer (EOC) with germline and pathogenic somatic BRCA1/2 mutations. However,...
PARP inhibitors (PARPi) are the maintenance therapy after first line platinum-based chemotherapy for patients with advanced epithelial ovarian cancer (EOC) with germline and pathogenic somatic BRCA1/2 mutations. However, as with chemotherapy, patients can develop resistance to PARPi. The selective pressure generated by heterogeneous somatic BRCA mutations may give rise to chemotherapy or PARPi resistant tumors. Here, we present the case of a patient harboring a pathogenic p.Glu143* (c.427G>T) somatic BRCA1 mutation conferring resistance to olaparib following cytoreductive surgery and platinum-based chemotherapy. We ordered a plasma ctDNA analysis (tissue biopsy of recurrent lesions was contraindicated due to their anatomical location) to figure out the possible resistance mechanism. Analysis of ctDNA did not detect the pathogenic somatic BRCA1 p.Glu143* (c.427G>T) mutation seen before. The tumor cells harboring the pathogenic BRCA1 mutation were probably eliminated by the platinum-based chemotherapy, leaving only those without BRCA mutations to proliferate.
Dysregulation of circRNA-0076906 and circRNA-0134944 is Correlated with Susceptibility to Osteoporosis and Osteoporotic Fracture in Postmenopausal Females from the Chinese Han Population.
Yang W, Zhang W, Li F … +2 more , Xu N, Sun P
Pharmgenomics Pers Med · 2023 · PMID 36926413 · Full text
INTRODUCTION: Many circRNAs, such as circRNA-0076906 and circRNA-0134944, have been reported to participate in the pathogenesis of osteoporosis via sponging miRNAs in postmenopausal female patients. In this study, we aim...
INTRODUCTION: Many circRNAs, such as circRNA-0076906 and circRNA-0134944, have been reported to participate in the pathogenesis of osteoporosis via sponging miRNAs in postmenopausal female patients. In this study, we aimed to study potential signaling pathways underlying the role of certain circRNAs, miRNAs and their target genes in the pathogenesis of osteoporotic fracture in postmenopausal females. METHODS: Quantitative real-time PCR was performed to analyze the expression of circRNAs, miRNAs and their targets genes. Luciferase assays were carried out to explore the regulatory relationship between circ_0076906/miR-548i/OGN and circ_0134944/miR-630/TLR4. RESULTS: Osteoporosis and fracture were positively correlated to the expression of circ_0134944, miR-548i and TLR4, but negatively correlated to the expression of circ_0076906, miR-630 and OGN in the peripheral blood and bone tissue samples of postmenopausal women. Luciferase activities of wild-type circ_0076906 and OGN were inhibited by miR-548i, and the luciferase activities of wild-type circ_0134944 and TLR4 were suppressed by miR-630 in MG-63 and U-2 OS cells. Inhibition of circ_0076906 expression in MG-63 and U-2 OS cells activated the expression of miR-548i and inhibited the expression of OGN. Moreover, the overexpression of circ_0134944 in MG-63 and U-2 OS cells suppressed the expression of miR-630 and enhanced the expression of TLR4. CONCLUSION: This study implied that the dysregulation of circRNA-0076906 and circRNA-0134944 modulated their specific signaling and thus contributed to the severity of osteoporosis, increasing the risk of osteoporotic fracture.
Detection of Novel Pathogenic Variants in Two Families with Recurrent Fetal Congenital Heart Defects.
Cai R, Tan Y, Wang M … +8 more , Yu H, Wang J, Ren Z, Dong Z, He Y, Li Z, Lin L, Gu Y
Pharmgenomics Pers Med · 2023 · PMID 36923242 · Full text
BACKGROUND: Congenital heart disease (CHD) is the most common birth defect with strong genetic heterogeneity. To date, about 400 genes have been linked to CHD, including cell signaling molecules, transcription factors, a...
BACKGROUND: Congenital heart disease (CHD) is the most common birth defect with strong genetic heterogeneity. To date, about 400 genes have been linked to CHD, including cell signaling molecules, transcription factors, and structural proteins that are important for heart development. Genetic analysis of CHD cases is crucial for clinical management and etiological analysis. METHODS: Whole-exome sequencing (WES) was performed to identify the genetic variants in two independent CHD cases with DNA samples from fetuses and their parents, followed by the exclusion of aneuploidy and large copy number variations (CNVs). The WES results were verified by Sanger sequencing. RESULTS: In family A, a compound heterozygous variation in gene consisting of c.1132dupA (p.I378fs) and c.1171C>T (p.R391C) was identified in the fetus. The two variants were inherited from the father (c.1132dupA) and the mother (c.1171C>T), respectively. In family B, a hemizygous variant : c.861delG (p.G289Afs*119) was identified in the fetus, which was inherited from the heterozygous mother. We further confirmed that these variants : c.1132dupA and : c.861delG were novel. CONCLUSION: The findings in our study identified novel variants to the mutation spectrum of CHD and provided reliable evidence for the recurrent risk and reproductive care options to the affected families. Our study also demonstrates that WES has considerable prospects of clinical application in prenatal diagnosis.
Nidogen-2 (NID2) is a Key Factor in Collagen Causing Poor Response to Immunotherapy in Melanoma.
Sha Y, Mao AQ, Liu YJ … +7 more , Li JP, Gong YT, Xiao D, Huang J, Gao YW, Wu MY, Shen H
Pharmgenomics Pers Med · 2023 · PMID 36908806 · Full text
BACKGROUND: The incidence of cutaneous melanoma continues to rise rapidly and has an extremely poor prognosis. Immunotherapy strategies are the most effective approach for patients who have developed metastases, but not...
BACKGROUND: The incidence of cutaneous melanoma continues to rise rapidly and has an extremely poor prognosis. Immunotherapy strategies are the most effective approach for patients who have developed metastases, but not all cases have been successful due to the complex and variable mechanisms of melanoma response to immune checkpoint inhibition. METHODS: We synthesized collagen-coding gene expression data (second-generation and single-cell sequencing) from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as Metascape database, Gene Set Cancer Analysis (GSCA) database, and Cytoscape software, etc., to investigate the biological mechanisms that may be related with collagens. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of Nidogen-2 (NID2). RESULTS: Melanoma patients can be divided into two collagen clusters. Patients with high collagen levels (C1) had a shorter survival than those with low collagen levels (C2) and were less likely to benefit from immunotherapy. We demonstrated that NID2 is a potential key factor in the collagen phenotype, is involved in fibroblast activation in melanoma, and forms a barrier to limit the proximity of CD8+ T cells to tumor cells. CONCLUSION: We clarified the adverse effects of collagen on melanoma patients and identified NID2 as a potential therapeutic target.
Hydroxychloroquine Ameliorates Hematuria in Children with X-Linked Alport Syndrome: Retrospective Case Series Study.
Sun L, Kuang XY, Zhang J … +1 more , Huang WY
Pharmgenomics Pers Med · 2023 · PMID 36874354 · Full text
PURPOSE: As a rare collagen type IV hereditary kidney disease, X-linked Alport syndrome (XLAS) is the most common form of Alport syndrome, the prevalence of which is estimated at 1:10,000 of the population, four times hi...
PURPOSE: As a rare collagen type IV hereditary kidney disease, X-linked Alport syndrome (XLAS) is the most common form of Alport syndrome, the prevalence of which is estimated at 1:10,000 of the population, four times higher than the prevalence rate of autosomal recessive Alport syndrome. To describe a series of eight XLAS children with persistent hematuria and proteinuria and the clinical outcomes after hydroxychloroquine (HCQ) treatment to assess its efficacy as early intervention. PATIENTS AND METHODS: The study retrospectively analysed 8 patients with persistent hematuria and proteinuria at different onset ages who were diagnosed with XLAS and been treated with HCQ. The urinary erythrocyte count, urinary albuminn were measured. Descriptive statistics were used to estimate the patients' responses to HCQ treatment after one month, three months, and six months. RESULTS: After the first month, the three months, and the six months of HCQ treatment, the urinary erythrocyte counts of four, seven, and eight children were significantly reduced; the decreasing proteinuria was found in two, four, and five children. Only one child with increasing proteinuria was found after 1-month HCQ treatment. This proteinuria was maintained after 3-month HCQ treatment but decreased to minor after 6-month HCQ treatment. CONCLUSION: We present the first potential efficacy of HCQ treatment in XLAS with hematuria and persistent proteinuria. It suggested that HCQ could be an effective treatment to ameliorate hematuria and proteinuria.
Genotypic and Phenotypic Composition of Sickle Cell Disease in the Arab Population - A Systematic Review.
Ata F, Rahhal A, Malkawi L … +10 more , Iqbal P, Khamees I, Alhiyari M, Yousaf Z, Qasim H, Alshurafa A, Sardar S, Javed S, Fernyhough L, Yassin M
Pharmgenomics Pers Med · 2023 · PMID 36851992 · Full text
UNLABELLED: Sickle cell disease (SCD) is a genetic disease influenced by ethnicity and regional differences in its clinical course. Recent advances in the management of SCD with newer therapies are being introduced to th...
UNLABELLED: Sickle cell disease (SCD) is a genetic disease influenced by ethnicity and regional differences in its clinical course. Recent advances in the management of SCD with newer therapies are being introduced to the Western population. However, many of these treatments are yet to be used in the Arabic SCD population. Understanding the genetic variations of SCD regionally is essential to anticipate the utilization of new treatments. This systematic review's main objective is to pool the available data on the genetic composition of SCD in the Arabic population. Data for 44,034 patients was extracted from 184 studies (11 case reports, 8 case series, 56 retrospectives, 107 prospective observational studies, and 2 clinical trials) using PubMed, Scopus, and Google Scholar. Male (49%) and female (51%) patients were equally reported wherever gender was available (N=13105). Various SCD genotypes were reported in a total of 14,257 patients, including Hb SS (77%) Hb Sβ0 (9.9%), and Hb Sβ+ (7.2%), while the rest of the genotypes, including HbSC, HbSD, HbSE, HbSO Arab, Hb S/α-Thal, Hb Sβ0 + α-Thal, and HBS Oman were individually reported in <4% of the cases. Major SCD complications in the Arab population included pain crises (48.25%) followed by neurological complications (33.46%), hepatobiliary complications (25.53%), musculoskeletal complications (24.73%), and hemolytic anemia (23.57%). The treatments reported for SCD included hydroxyurea (20%), blood transfusion (14.32%), and Deferasirox (3.03%). We did not find the use of stem cell transplantation or newer treatments such as L-Glutamine, Voxelotor, Crizanlizumab, or gene therapy reported in any of the studies included in our review. This review highlights the genetic makeup of SCD in Arab countries and its common phenotypic manifestations and will help direct further research on SCD in this region, especially concerning genetic therapy. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered in the International Prospective Register of Systematic Reviews(PROSPERO):CRD42020218,666. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=218666.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe