Kang Huang, Tianyi Ma, Qiang Li, Zanrui Zhong, Ting Qin, Yilei Zhou, Wei Zhang, Shilin Tang, Jianghua Zhong, Shijuan Lu
Introduction: Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of CYP19A1 single nucleotide polymorphisms (SNPs) in IS in the Chinese population.
Methods: 1302 subjects (651 controls and 651 cases) were recruited in this case-control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of CYP19A1 were selected by the 1000 genomes project database. The association between CYP19A1 SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk.
Results: In the research, CYP19A1 loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24.
Conclusion: The study revealed that there is a significant association between CYP19A1 loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.
{"title":"Role of <i>CYP19A1</i> Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population.","authors":"Kang Huang, Tianyi Ma, Qiang Li, Zanrui Zhong, Ting Qin, Yilei Zhou, Wei Zhang, Shilin Tang, Jianghua Zhong, Shijuan Lu","doi":"10.2147/PGPM.S404160","DOIUrl":"https://doi.org/10.2147/PGPM.S404160","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic stroke (IS) is a multifactorial and polygenic disease, which is affected by genetic factors. In this study, we explored the role of <i>CYP19A1</i> single nucleotide polymorphisms (SNPs) in IS in the Chinese population.</p><p><strong>Methods: </strong>1302 subjects (651 controls and 651 cases) were recruited in this case-control study. Four candidate SNPs (rs28757157 C/T, rs3751592 C/T, rs3751591 G/A, rs59429575 C/T) of <i>CYP19A1</i> were selected by the 1000 genomes project database. The association between <i>CYP19A1</i> SNPs and IS risk was assessed using logistic regression analysis with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis further verified the positive results. The interaction of SNP-SNP was analyzed by multi-factor dimensionality reduction (MDR) to predict is risk.</p><p><strong>Results: </strong>In the research, <i>CYP19A1</i> loci (rs28757157 and rs3751591) were associated with the occurrence of IS. The two variants conferred an increased susceptibility to IS in the subjects aged over 60 years old, smokers and drinkers. Rs28757157 was related to the risk of IS in females, non-smokers and subjects with BMI less than 24, while rs59429575 was related to the risk of IS in males and subjects with BMI greater than 24.</p><p><strong>Conclusion: </strong>The study revealed that there is a significant association between <i>CYP19A1</i> loci (rs28757157 and rs3751591) and IS risk in the Chinese Han population, providing a theoretical basis for further exploring its specific role in the pathogenesis of IS.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"491-502"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/16/10/pgpm-16-491.PMC10237203.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9951394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuegang Wang, Weiquan Li, Ning Lou, Weiwei Han, Bo Hai, Wen Xiao, Xiaoping Zhang
Background: Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC.
Methods: Kaplan-Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC.
Results: DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC.
Conclusion: This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.
背景:透明细胞肾细胞癌(ccRCC)患者的侵袭和转移导致预后不良和死亡。据报道,脱氧核苷酸转移酶末端相互作用蛋白1 (DNTTIP1)可促进多发性肿瘤的进展。然而,目前还没有关于DNTTIP1在ccRCC中的研究。方法:通过Kaplan-Meier生存分析、多因素分析,验证了肿瘤基因组图谱肾透明细胞癌(TCGA-KIRC)中DNTTIP1表达的ccRCC的预后指标总生存期(OS)和无病生存期(DFS)。ROC曲线分析DNTTIP1在TCGA-KIRC和验证数据集中的诊断能力。采用实时定量聚合酶链反应(qRT-PCR)检测DNTTIP1在肾癌组织中的表达,并由美国癌症临床蛋白质组学研究办公室(Office of cancer Clinical Proteomics Research, CPTAC)验证DNTTIP1的蛋白表达。此外,nomogram预测了DNTTIP1在ccRCC患者中的作用。单样本基因集富集分析(SsGSEA)和GSEA评估了DNTTIP1在TCGA-KIRC中的发病机制。结果:DNTTIP1在ccRCC肿瘤组织中表达较高。DNTTIP1高表达与不良OS (HR = 1.618, P < 0.0001)和不良DFS (HR = 1.789, P < 0.0001)相关。SsGSEA和GSEA显示DNTTIP1与缺氧、上皮-间质转化(EMT)、血管生成、G2M检查点相关。DNTTIP1与ccRCC中EMT生物标志物呈正相关,可能是ccRCC的有效靶点。结论:本研究提示DNTTIP1的高表达预示着ccRCC的不良预后,DNTTIP1可能是未来肿瘤恶性的新的检测生物标志物和治疗靶点。
{"title":"High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma.","authors":"Xuegang Wang, Weiquan Li, Ning Lou, Weiwei Han, Bo Hai, Wen Xiao, Xiaoping Zhang","doi":"10.2147/PGPM.S382843","DOIUrl":"https://doi.org/10.2147/PGPM.S382843","url":null,"abstract":"<p><strong>Background: </strong>Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC.</p><p><strong>Methods: </strong>Kaplan-Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC.</p><p><strong>Results: </strong>DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC.</p><p><strong>Conclusion: </strong>This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"1-14"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/80/pgpm-16-1.PMC9831534.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9091814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Resistance to PARP Inhibitors After First-Line Platinum-Based Chemotherapy in a Patient with Advanced Ovarian Cancer with a Pathogenic Somatic BRCA1 Mutation.","authors":"Lan Zhong, Rutie Yin, Liang Song","doi":"10.2147/PGPM.S397827","DOIUrl":"https://doi.org/10.2147/PGPM.S397827","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"195-200"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f6/05/pgpm-16-195.PMC10024533.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9149899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with an immunosuppressive Tumor microenvironment (TME). Ferroptosis plays an essential role in tumor proliferation, invasion, and metastasis. However, the relationship between ferroptosis and TME of HCC has remained elusive.
Methods: Differentially expressed ferroptosis-related genes (DE FRGs) between normal liver tissues and HCC tissues were obtained from The Cancer Genome Atlas (TCGA). On this basis, we identified the molecular subtypes mediated by DE FRGs and TME cell infiltration. Next, a predictive signature was established to quantity the ferroptosis-related characteristics by performing the least absolute shrinkage and selection operator Cox regression analyses. Univariate and multivariate COX analyses determined the independent prognostic factors. Finally, the expression stability of 3 ferroptosis-related signature genes was verified in cancer and paracancerous normal tissues of HCC.
Results: We identified three different molecular subtypes and found that the subtype with the better prognosis was associated with high enrichment of immune- and metabolic-related hallmark signaling pathways and high infiltration of immune cells in TME. The signature was considered to be an independent prognostic factor. We also found that the signature can reflect the infiltration characteristics of different immune cells in TME. Immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), regulatory T cells, and type 17 T helper cells were significantly enriched in the high-risk group. The analysis data of immune checkpoints and tumor mutation load indicated that the signature had great potential in predicting Immunotherapy response and chemotherapeutic sensitivity. In addition, the overexpression of 3 ferroptosis-related signature genes was confirmed in HCC tissues and HCC cell lines. Ferroptosis inducer RSL3 inhibited the proliferation of HCC cells and was a potential cancer immunotherapy agent.
Conclusion: These findings enhanced our understanding of the regulatory mechanism of ferroptosis in HCC and provided new insights into evaluating prognosis and developing more effective Immunotherapy and chemotherapy strategies.
{"title":"Identification and Validation of Ferroptosis-Related Subtypes and a Predictive Signature in Hepatocellular Carcinoma.","authors":"Chunlan Zheng, Yanan Peng, Haizhou Wang, Youwei Wang, Lan Liu, Qiu Zhao","doi":"10.2147/PGPM.S397892","DOIUrl":"https://doi.org/10.2147/PGPM.S397892","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with an immunosuppressive Tumor microenvironment (TME). Ferroptosis plays an essential role in tumor proliferation, invasion, and metastasis. However, the relationship between ferroptosis and TME of HCC has remained elusive.</p><p><strong>Methods: </strong>Differentially expressed ferroptosis-related genes (DE FRGs) between normal liver tissues and HCC tissues were obtained from The Cancer Genome Atlas (TCGA). On this basis, we identified the molecular subtypes mediated by DE FRGs and TME cell infiltration. Next, a predictive signature was established to quantity the ferroptosis-related characteristics by performing the least absolute shrinkage and selection operator Cox regression analyses. Univariate and multivariate COX analyses determined the independent prognostic factors. Finally, the expression stability of 3 ferroptosis-related signature genes was verified in cancer and paracancerous normal tissues of HCC.</p><p><strong>Results: </strong>We identified three different molecular subtypes and found that the subtype with the better prognosis was associated with high enrichment of immune- and metabolic-related hallmark signaling pathways and high infiltration of immune cells in TME. The signature was considered to be an independent prognostic factor. We also found that the signature can reflect the infiltration characteristics of different immune cells in TME. Immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs), regulatory T cells, and type 17 T helper cells were significantly enriched in the high-risk group. The analysis data of immune checkpoints and tumor mutation load indicated that the signature had great potential in predicting Immunotherapy response and chemotherapeutic sensitivity. In addition, the overexpression of 3 ferroptosis-related signature genes was confirmed in HCC tissues and HCC cell lines. Ferroptosis inducer RSL3 inhibited the proliferation of HCC cells and was a potential cancer immunotherapy agent.</p><p><strong>Conclusion: </strong>These findings enhanced our understanding of the regulatory mechanism of ferroptosis in HCC and provided new insights into evaluating prognosis and developing more effective Immunotherapy and chemotherapy strategies.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"39-58"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/be/pgpm-16-39.PMC9885776.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10633234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
简介与目的:丝裂原活化蛋白激酶(MAPK)通路被泛靶点抑制剂Anlotinib抑制,诱导肿瘤细胞死亡。除了常见的凋亡和坏死外,近年来还出现了一种肿瘤细胞死亡的焦亡模式,主要表现为gasdermin蛋白(GSDMs)的裂解。Gasdermin B (GSDMB)参与膀胱癌的进展和预后。Anlotinib治疗gsdmb阳性膀胱肿瘤的疗效及作用机制至今未见研究。方法:从TCGA膀胱癌数据库中分析GSDMB表达与肿瘤分期、总生存率、免疫治疗应答、肿瘤复发及进展率的关系。应用Anlotinib治疗小鼠gsdmb阳性膀胱癌,然后流式分析与焦亡相关的炎性因子分泌及抗肿瘤因子水平。Western blot分析检测了MAPK和MEK信号转导通路。结果:TCGA数据分析显示,GSDMB高表达膀胱癌患者的总生存率优于GSDMB低表达膀胱癌患者。体内实验表明,Anlotinib治疗gsdmb阳性膀胱癌比gsdmb阴性膀胱癌更有效。Anlotinib可增加gsdmb阳性膀胱癌中TNF-a、CD107a等抗肿瘤相关因子的分泌。此外,Anlotinib还诱导GSDMB蛋白表达增加。安洛替尼治疗gsdmb阳性膀胱癌可降低参与安洛替尼信号转导通路的AKT和MEK蛋白的表达。结论:安洛替尼对gsdmb阳性膀胱肿瘤具有较强的抗肿瘤作用。这种作用主要是通过anlotinib刺激淋巴细胞分泌相关抗肿瘤因子来实现的。在表达GSDMB蛋白的膀胱癌中,Anlotinib可抑制PI3K/AKT和MEK信号转导通路。
{"title":"Anlotinib Enhances the Therapeutic Effect of Bladder Cancer with GSDMB Expression: Analyzed from TCGA Bladder Cancer Database & Mouse Bladder Cancer Cell Line.","authors":"Chen Wang, Qifeng Cao, Shun Zhang, Hailong Liu, Huangqi Duan, Weimin Xia, Haibo Shen, Cheng Wang","doi":"10.2147/PGPM.S398451","DOIUrl":"https://doi.org/10.2147/PGPM.S398451","url":null,"abstract":"<p><strong>Introduction and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"219-228"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/8a/pgpm-16-219.PMC10029935.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9171994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bo Gao, Rui Li, Xiaojia Song, Shan Hu, Fengmei Yang
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.
{"title":"miR-139-5p and miR-451a as a Diagnostic Biomarker in LUSC.","authors":"Bo Gao, Rui Li, Xiaojia Song, Shan Hu, Fengmei Yang","doi":"10.2147/PGPM.S402750","DOIUrl":"https://doi.org/10.2147/PGPM.S402750","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"313-323"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/7a/pgpm-16-313.PMC10093518.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9309477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiangfen Wu, Lingyan Ren, Xinyi Huang, Li Hu, Liangliang Zhang, Dan Xie, Zhimin Li, Naijian Han, Shengwen Huang
Background: Duchenne muscular dystrophy (DMD), an X-linked recessive neuromuscular disorder, is caused by pathogenic variants in the DMD gene encoding a large structural protein in muscle cells.
Methods: Two probands, a 6-year old boy and a 1-month old infant, respectively, were clinically diagnosed with DMD based on elevated levels of creatine kinase and creatine kinase isoenzyme. CNVplex and whole exome sequencing (WES) were performed for causal variants, and Sanger sequencing was used for verification.
Results: CNVplex found no large deletions or duplications in the DMD gene in both patients, but WES discovered a single-nucleotide deletion in exon 48 (NM_004006.2:c.6963del, p.Asp2322ThrfsTer16) in the proband of pedigree 1, and a nonsense mutation in exon 27 (NM_004006.2:c.3637A>T, p.K1213Ter) in the proband of pedigree 2.
Conclusion: The results of our study expand the mutation spectrum of DMD and enrich our understanding of the clinical characteristics of DMD. Genetic counseling was provided for the two families involved in this study.
{"title":"Identification of Two Novel Variants of the <i>DMD</i> Gene in Chinese Families with Duchenne Muscular Dystrophy.","authors":"Jiangfen Wu, Lingyan Ren, Xinyi Huang, Li Hu, Liangliang Zhang, Dan Xie, Zhimin Li, Naijian Han, Shengwen Huang","doi":"10.2147/PGPM.S416294","DOIUrl":"https://doi.org/10.2147/PGPM.S416294","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD), an X-linked recessive neuromuscular disorder, is caused by pathogenic variants in the <i>DMD</i> gene encoding a large structural protein in muscle cells.</p><p><strong>Methods: </strong>Two probands, a 6-year old boy and a 1-month old infant, respectively, were clinically diagnosed with DMD based on elevated levels of creatine kinase and creatine kinase isoenzyme. CNVplex and whole exome sequencing (WES) were performed for causal variants, and Sanger sequencing was used for verification.</p><p><strong>Results: </strong>CNVplex found no large deletions or duplications in the <i>DMD</i> gene in both patients, but WES discovered a single-nucleotide deletion in exon 48 (NM_004006.2:c.6963del, p.Asp2322ThrfsTer16) in the proband of pedigree 1, and a nonsense mutation in exon 27 (NM_004006.2:c.3637A>T, p.K1213Ter) in the proband of pedigree 2.</p><p><strong>Conclusion: </strong>The results of our study expand the mutation spectrum of DMD and enrich our understanding of the clinical characteristics of DMD. Genetic counseling was provided for the two families involved in this study.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"759-766"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/c8/pgpm-16-759.PMC10441636.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10413897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Judith Wellens, Eva Vissers, Christophe Matthys, Séverine Vermeire, João Sabino
Inflammatory bowel diseases (IBD) are chronic and incurable conditions of the gastro-intestinal tract with an increasing incidence and prevalence worldwide. Common symptoms are abdominal pain, diarrhea, and weight loss. Despite recent advances in medical management, many patients fail to achieve clinical remission and healing of the mucosa of the bowel. The cause is thought to involve an inappropriate reaction of the immune system, the microbiome and the environment in genetically susceptible individuals, leading to chronic bowel inflammation. Evidence is emerging that diet is a key environmental factor that might influence disease onset and course, and therefore may become a therapeutic strategy to mitigate inflammation and symptoms. Since IBD is a heterogeneous disease on a clinical and a molecular level, personalizing dietary advice could be the crucial factor to achieve long-lasting changes in dietary behaviors that could not only improve nutritional status but also tackle gut inflammation and abdominal symptoms on an individual level. In this review, we first discuss different aspects of personalized nutrition, namely the level, focus, and scope of personalized dietary regimens. Then, we provide a framework for the different goals of nutritional therapy in IBD and current evidence for personalized dietary approaches. Lastly, we discuss the need for adequate trial designs, access to the right data types and the bioinformatic tools that are necessary to develop algorithms that will allow us to move from general "healthy eating" advice to truly personalized nutritional plans for the individual IBD patient.
{"title":"Personalized Dietary Regimens for Inflammatory Bowel Disease: Current Knowledge and Future Perspectives.","authors":"Judith Wellens, Eva Vissers, Christophe Matthys, Séverine Vermeire, João Sabino","doi":"10.2147/PGPM.S359365","DOIUrl":"https://doi.org/10.2147/PGPM.S359365","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBD) are chronic and incurable conditions of the gastro-intestinal tract with an increasing incidence and prevalence worldwide. Common symptoms are abdominal pain, diarrhea, and weight loss. Despite recent advances in medical management, many patients fail to achieve clinical remission and healing of the mucosa of the bowel. The cause is thought to involve an inappropriate reaction of the immune system, the microbiome and the environment in genetically susceptible individuals, leading to chronic bowel inflammation. Evidence is emerging that diet is a key environmental factor that might influence disease onset and course, and therefore may become a therapeutic strategy to mitigate inflammation and symptoms. Since IBD is a heterogeneous disease on a clinical and a molecular level, personalizing dietary advice could be the crucial factor to achieve long-lasting changes in dietary behaviors that could not only improve nutritional status but also tackle gut inflammation and abdominal symptoms on an individual level. In this review, we first discuss different aspects of personalized nutrition, namely the level, focus, and scope of personalized dietary regimens. Then, we provide a framework for the different goals of nutritional therapy in IBD and current evidence for personalized dietary approaches. Lastly, we discuss the need for adequate trial designs, access to the right data types and the bioinformatic tools that are necessary to develop algorithms that will allow us to move from general \"healthy eating\" advice to truly personalized nutritional plans for the individual IBD patient.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"15-27"},"PeriodicalIF":1.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/ef/pgpm-16-15.PMC9842524.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10554504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-02eCollection Date: 2022-01-01DOI: 10.2147/PGPM.S338601
Innocent G Asiimwe, Munir Pirmohamed
Cardiovascular disease remains a leading cause of both morbidity and mortality worldwide. It is widely accepted that both concomitant medications (drug-drug interactions, DDIs) and genomic factors (drug-gene interactions, DGIs) can influence cardiovascular drug-related efficacy and safety outcomes. Although thousands of DDI and DGI (aka pharmacogenomic) studies have been published to date, the literature on drug-drug-gene interactions (DDGIs, cumulative effects of DDIs and DGIs) remains scarce. Moreover, multimorbidity is common in cardiovascular disease patients and is often associated with polypharmacy, which increases the likelihood of clinically relevant drug-related interactions. These, in turn, can lead to reduced drug efficacy, medication-related harm (adverse drug reactions, longer hospitalizations, mortality) and increased healthcare costs. To examine the extent to which DDGIs and other interactions influence efficacy and safety outcomes in the field of cardiovascular medicine, we review current evidence in the field. We describe the different categories of DDIs and DGIs before illustrating how these two interact to produce DDGIs and other complex interactions. We provide examples of studies that have reported the prevalence of clinically relevant interactions and the most implicated cardiovascular medicines before outlining the challenges associated with dealing with these interactions in clinical practice. Finally, we provide recommendations on how to manage the challenges including but not limited to expanding the scope of drug information compendia, interaction databases and clinical implementation guidelines (to include clinically relevant DDGIs and other complex interactions) and work towards their harmonization; better use of electronic decision support tools; using big data and novel computational techniques; using clinically relevant endpoints, preemptive genotyping; ensuring ethnic diversity; and upskilling of clinicians in pharmacogenomics and personalized medicine.
{"title":"Drug-Drug-Gene Interactions in Cardiovascular Medicine.","authors":"Innocent G Asiimwe, Munir Pirmohamed","doi":"10.2147/PGPM.S338601","DOIUrl":"10.2147/PGPM.S338601","url":null,"abstract":"<p><p>Cardiovascular disease remains a leading cause of both morbidity and mortality worldwide. It is widely accepted that both concomitant medications (drug-drug interactions, DDIs) and genomic factors (drug-gene interactions, DGIs) can influence cardiovascular drug-related efficacy and safety outcomes. Although thousands of DDI and DGI (aka pharmacogenomic) studies have been published to date, the literature on drug-drug-gene interactions (DDGIs, cumulative effects of DDIs and DGIs) remains scarce. Moreover, multimorbidity is common in cardiovascular disease patients and is often associated with polypharmacy, which increases the likelihood of clinically relevant drug-related interactions. These, in turn, can lead to reduced drug efficacy, medication-related harm (adverse drug reactions, longer hospitalizations, mortality) and increased healthcare costs. To examine the extent to which DDGIs and other interactions influence efficacy and safety outcomes in the field of cardiovascular medicine, we review current evidence in the field. We describe the different categories of DDIs and DGIs before illustrating how these two interact to produce DDGIs and other complex interactions. We provide examples of studies that have reported the prevalence of clinically relevant interactions and the most implicated cardiovascular medicines before outlining the challenges associated with dealing with these interactions in clinical practice. Finally, we provide recommendations on how to manage the challenges including but not limited to expanding the scope of drug information compendia, interaction databases and clinical implementation guidelines (to include clinically relevant DDGIs and other complex interactions) and work towards their harmonization; better use of electronic decision support tools; using big data and novel computational techniques; using clinically relevant endpoints, preemptive genotyping; ensuring ethnic diversity; and upskilling of clinicians in pharmacogenomics and personalized medicine.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"15 ","pages":"879-911"},"PeriodicalIF":1.9,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/5c/pgpm-15-879.PMC9639705.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianpin Ye, Zhiwei Zeng, Yuxian Chen, Zhenkun Wu, Qingwei Yang, Tao Sun
Background Both genetic and environmental factors strongly affect serum uric acid (SUA) concentrations. The incidence of hyperuricemia tends to be younger in the Chinese population. In particular, we have found a high prevalence of hyperuricemia among Chinese flight attendants, aged from 20 to 40, in our survey. This study aims to evaluate whether there is an association between gene polymorphisms and hyperuricemia among Chinese flight attendants. Methods A total of 532 flight attendants with high and normal serum uric acid levels were recruited. Allele-specific polymerase chain reaction (AS-PCR) was performed using blood samples of enrolled subjects. Results Previous studies have reported single nucleotide polymorphisms (SNPs) that are tightly associated with uric acid levels. Among them, six SNPs that are strongly associated with SUA or gout in Asians, for instance ABCG2 (rs2231142, rs72552713 and rs2231137), GCKR (rs780094), SLC2A9 (rs1014290) and SLC17A1 (rs1183201), were selected for AS-PCR analyses. We found that SNPs such as ABCG2 rs2231142, GCKR rs780094 and SLC2A9 rs1014290 are strongly associated with hyperuricemia in male flight attendants, and SLC2A9 rs1014290 among female flight attendants. Conclusion Our study provides evidences of an association between SNPs and hyperuricemia in the Chinese flight attendants, and highlights the significance of improving diagnostics and prevention of disease development in uric acid metabolism disorders and gout using these SNPs.
{"title":"Examining an Association of Single Nucleotide Polymorphisms with Hyperuricemia in Chinese Flight Attendants","authors":"Jianpin Ye, Zhiwei Zeng, Yuxian Chen, Zhenkun Wu, Qingwei Yang, Tao Sun","doi":"10.2147/PGPM.S364206","DOIUrl":"https://doi.org/10.2147/PGPM.S364206","url":null,"abstract":"Background Both genetic and environmental factors strongly affect serum uric acid (SUA) concentrations. The incidence of hyperuricemia tends to be younger in the Chinese population. In particular, we have found a high prevalence of hyperuricemia among Chinese flight attendants, aged from 20 to 40, in our survey. This study aims to evaluate whether there is an association between gene polymorphisms and hyperuricemia among Chinese flight attendants. Methods A total of 532 flight attendants with high and normal serum uric acid levels were recruited. Allele-specific polymerase chain reaction (AS-PCR) was performed using blood samples of enrolled subjects. Results Previous studies have reported single nucleotide polymorphisms (SNPs) that are tightly associated with uric acid levels. Among them, six SNPs that are strongly associated with SUA or gout in Asians, for instance ABCG2 (rs2231142, rs72552713 and rs2231137), GCKR (rs780094), SLC2A9 (rs1014290) and SLC17A1 (rs1183201), were selected for AS-PCR analyses. We found that SNPs such as ABCG2 rs2231142, GCKR rs780094 and SLC2A9 rs1014290 are strongly associated with hyperuricemia in male flight attendants, and SLC2A9 rs1014290 among female flight attendants. Conclusion Our study provides evidences of an association between SNPs and hyperuricemia in the Chinese flight attendants, and highlights the significance of improving diagnostics and prevention of disease development in uric acid metabolism disorders and gout using these SNPs.","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"15 1","pages":"589 - 602"},"PeriodicalIF":1.9,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42850033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}