Pharmacogenomics & Personalized Medicine最新文献

{"title":"Leucyl and Cystinyl Aminopeptidase as a Prognostic-Related Biomarker in OV Correlating with Immune Infiltrates.","authors":"Qian Ma,&nbsp;Lei Chang,&nbsp;Wenwen Wang,&nbsp;Lingyi Che,&nbsp;Xiaoqin Song,&nbsp;Gailing Li,&nbsp;Ying Zhang,&nbsp;Yibing Chen,&nbsp;Zhuoyu Gu,&nbsp;Xin Ge","doi":"10.2147/PGPM.S400145","DOIUrl":"https://doi.org/10.2147/PGPM.S400145","url":null,"abstract":"<p><strong>Background: </strong>It was indicated that tumor intrinsic heterogeneity and the tumor microenvironment (TME) of ovarian cancer (OV) influence immunotherapy efficacy and patient outcomes. Leucyl and cystinyl aminopeptidase (LNPEP) encodes a zinc-dependent aminopeptidase, which has been proved to participant in the vesicle-mediated transport and class I MHC mediated antigen processing and presentation. However, the function of LNPEP in TME of OV and its potential molecular mechanisms have not been determined. Therefore, we aimed to investigate a prognostic biomarker which may be helpful in identifying TME heterogeneity of ovarian cancer.</p><p><strong>Methods: </strong>In this study, bioinformatics databases were used to explore the expression profile and immune infiltration of LNPEP. Bioinformatics analyses of survival data and interactors of LNPEP were conducted to predict the prognostic value of LNPEP in OV. The protein levels of LNPEP were validated by Western blot and immunohistochemistry.</p><p><strong>Results: </strong>Based on the TCGA data, our data displayed that the mRNA expression of LNPEP was markedly down-regulated in ovarian cancer than that in para-cancer tissues, contrary to the protein level. Importantly, high LNPEP expression was associated with poor prognosis in patients with OV. Furthermore, Cox regression analysis showed that LNPEP was an independent prognostic factor in OV. GO and KEGG pathway analyses indicated the co-expressed genes of LNPEP were mainly related to a variety of immune-related pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, and immunoregulatory interaction. Our data also demonstrated that the expression of LNPEP was strongly correlated with immune infiltration levels, immunomodulators, chemokines and chemokine receptors.</p><p><strong>Conclusion: </strong>In our study, we identified and established a prognostic signature of immune-related LNPEP in OV, which will be of great value in predicting the prognosis of clinical trials and may become a new therapeutic target for immunological research and potential prognostic biomarker in OV.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"551-568"},"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/63/99/pgpm-16-551.PMC10244028.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9613502","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}

{"title":"Exploring the Correlation Between <i>GPR176</i>, a Potential Target Gene of Gastric Cancer, and Immune Cell Infiltration.","authors":"Xianhua Gu,&nbsp;Honghong Shen,&nbsp;Zheng Xiang,&nbsp;Xinwei Li,&nbsp;Yue Zhang,&nbsp;Rong Zhang,&nbsp;Fang Su,&nbsp;Zishu Wang","doi":"10.2147/PGPM.S411199","DOIUrl":"https://doi.org/10.2147/PGPM.S411199","url":null,"abstract":"<p><strong>Introduction: </strong><i>GPR176</i>, an orphan G protein-coupled receptor (GPCR), is essential for the progression of gastrointestinal cancers. However, it is still unclear how <i>GPR176</i> affects tumor immunity and patient prognosis in gastric cancer (GC).</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were searched in this investigation to assess the expression patterns of <i>GPR176</i> in GC tissues and normal gastric mucosa. The findings were further verified using immunohistochemical tests and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method, univariate logistic regression, and Cox regression were then used to investigate the relationship between <i>GPR176</i> and clinical traits. Additionally, the potential correlation between <i>GPR176</i>, immune checkpoint genes, and immune cell infiltration levels was investigated.</p><p><strong>Results: </strong>As per the research findings, GC tissues had higher levels of <i>GPR176</i> than normal tissues. Additionally, individuals with high expression of <i>GPR176</i> had a worse 10-year overall survival (OS), in contrast with those having a low expression of <i>GPR176</i> (<i>p</i> < 0.001). The OS of GC can be predicted using a validated nomogram model. The expression of <i>GPR176</i> demonstrated a negative correlation with CD8+ T cells. When compared to the low-expression group of <i>GPR176</i>, Tumor Immune Dysfunction and Exclusion (TIDE) analysis demonstrated that the high-expression group had a considerably higher risk of immune evasion. A remarkable difference (variation) was observed in the levels of <i>GPR176</i> expression across both groups, ie, low and high-risk groups, as determined by the immune phenomenon scores (IPS) immunotherapy assessment.</p><p><strong>Conclusion: </strong>By examining <i>GPR176</i> from various biological perspectives, it was determined that <i>GPR176</i> can act as a predictive biomarker for poor patient prognosis in GC. Additionally, it was observed that <i>GPR176</i> is capable of suppressing the proliferation of CD8+ T cells and facilitating immune evasion.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"519-535"},"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/43/db/pgpm-16-519.PMC10241216.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9645597","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}

{"title":"Exploration into Plasma Hsa_circ_0052184 as a New Biomarker of Colorectal Cancer Prognosis.","authors":"Enqi Zheng,&nbsp;Deshuang Xiao","doi":"10.2147/PGPM.S413451","DOIUrl":"https://doi.org/10.2147/PGPM.S413451","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) are strong modulators of tumor pathology. Herein, our goal was to examine the plasma hsa_circ_0052184 content among colorectal cancer (CRC) patients, and assess its association with patient clinicopathological profile and diagnostic values.</p><p><strong>Methods: </strong>Overall, we collected 228 presurgical CRC and 146 normal plasma samples from The First People's Hospital of Wenling. Circulating hsa_circ_0052184 levels were assessed via qRT-PCR, and the diagnostic prediction was conducted with the receiver operating characteristic (ROC) curve.</p><p><strong>Results: </strong>Relative to healthy controls, CRC patients exhibited markedly enhanced circulating hsa_circ_0052184 levels, which were closely correlated with advanced stage of disease and worse outcome. Based on our uni- (UA) and multivariate assessments (MA), elevated hsa_circ_0052184 levels were a stand-alone predictor of poor prognosis. The ROC curve depicted an area under the curve (AUC) for CRC diagnosis to be 0.9072.</p><p><strong>Conclusion: </strong>Circulating hsa_circ_0052184 is a potential bioindicator of CRC outcome.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"589-597"},"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/74/77/pgpm-16-589.PMC10275319.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9654390","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}

{"title":"Pyroptosis and Inflammasome-Related Genes-<i>NLRP3, NLRC4</i> and <i>NLRP7</i> Polymorphisms Were Associated with Risk of Lung Cancer.","authors":"Xin Jing,&nbsp;Yuhui Yun,&nbsp;Xiang Ji,&nbsp;Ende Yang,&nbsp;Pei Li","doi":"10.2147/PGPM.S424326","DOIUrl":"https://doi.org/10.2147/PGPM.S424326","url":null,"abstract":"<p><strong>Background: </strong>Cancer development and tumor immune microenvironment remodeling are closely linked to pyroptosis and inflammasome activation. However, little information is available in single nucleotide polymorphisms (SNPs) in pyroptosis and inflammasome-related genes in patients with lung cancer. This study aims to evaluate the associations between pyroptosis-related gene (<i>NLRP3, NLRC4,</i> and <i>NLRP7</i>) polymorphisms and the risk of lung cancer.</p><p><strong>Methods: </strong>The MassARRAY platform was used to genotype six SNPs of the <i>NLRP3, NLRC4,</i> and <i>NLRP7</i> genes in 660 lung cancer cases and 660 controls.</p><p><strong>Results: </strong>Individuals with rs35829419-A, rs385076-C, and rs775882-T alleles exhibited a higher risk of lung cancer (<i>p</i> < 0.01), while rs212704-T appears protective (<i>p</i> = 0.006). The rs35829419-AA, rs385076-TC/CC, and rs775882-CT/TT genotypes were associated with various degrees of elevated risk of lung cancer (<i>p</i><0.02), whereas rs212704-TT was associated with a reduced risk of the disease (<i>p</i>=0.014). Genetic models analysis showed that rs35829419, rs385076, and rs775882 was associated with an increased risk of lung cancer, while rs212704 was related to a reduced risk in all three models (<i>p</i> < 0.05). The four SNPs remained significant in smoker and nonsmoker subgroups (<i>p</i> < 0.05). However, rs35829419 was correlated with risk of adenocarcinoma and small cell lung cancer, and rs212704 was only protective for squamous cell carcinoma. The rs385076 and rs775882 were associated with all three pathological types (<i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>Besides providing candidate markers for identification of high-risk populations and early prevention of the disease, our research also provided new insight into anti-tumor strategies targeting inflammasomes and pyroptosis.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"795-804"},"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/25/87/pgpm-16-795.PMC10464886.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10482816","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}

{"title":"Clinical Knowledge, Attitude, and Perceptions of Community Pharmacists Towards Pharmacogenomics - A Cross-Sectional Study from Saudi Arabia.","authors":"Ziyad Alrabiah,&nbsp;Wajid Syed,&nbsp;Salmeen D Babelghaith,&nbsp;Mohamed N Al Arifi","doi":"10.2147/PGPM.S403655","DOIUrl":"https://doi.org/10.2147/PGPM.S403655","url":null,"abstract":"<p><strong>Background and aims: </strong>It is crucial to provide healthcare personnel with the necessary knowledge and understanding of genetic testing and pharmacogenomics. The purpose of this study is to assess the knowledge, attitudes, views, and considerations of Community pharmacists (CPs) about pharmacogenomics and genetics.</p><p><strong>Methods and materials: </strong>A cross-sectional web-based study was conducted among practicing pharmacists Between January and February of 2022. Participants were recruited through a convenient sampling technique. A total of 23 item questionnaires were used to assess the Knowledge Attitudes, Views, and Considerations toward Pharmacogenomics among pharmacists.</p><p><strong>Results: </strong>The mean age of the CPs were 28.45±7.29(Std). Among the CPs, 38.4% (98 of 255) of them were correctly identified human chromosomes, and the majority of them 73.3% knew that adverse reactions can be caused by genetic changes in the human body. A total of 194 CPs agreed that certain drugs can be affected by genetic changes in the patient. In this study, one-third (33%) of the CPs were found to have good knowledge, while most (66.3%) of the CPs were found poor knowledge of pharmacogenomics and genetics. Furthermore, the knowledge score is significantly different concerning the qualification of the CPs (<i>p</i>=0.0001).</p><p><strong>Conclusion: </strong>The current findings, demonstrated a majority of the CPs found a lack of knowledge and understanding regarding pharmacogenomics and its perspectives, there is a need to increase awareness among CPs to reduce the knowledge gap of pharmacogenomics and genetics.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"433-441"},"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/53/b9/pgpm-16-433.PMC10179052.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9829685","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}

{"title":"Are We Ready for Whole Population Genomic Sequencing of Asymptomatic Newborns?","authors":"Danya F Vears,&nbsp;Julian Savulescu,&nbsp;John Christodoulou,&nbsp;Meaghan Wall,&nbsp;Ainsley J Newson","doi":"10.2147/PGPM.S376083","DOIUrl":"https://doi.org/10.2147/PGPM.S376083","url":null,"abstract":"<p><p>The introduction of genomic sequencing technologies into routine newborn screening programs in some form is not only inevitable but also already occurring in some settings. The question is therefore not \"if\" but \"when and how\" genomic newborn screening (GNBS) should be implemented. In April 2022, the Centre for Ethics of Paediatric Genomics held a one-day symposium exploring ethical issues relating to the use of genomic sequencing in a range of clinical settings. This review article synthesises the panel discussion and presents both the potential benefits of wide-scale implementation of genomic newborn screening, as well as its practical and ethical issues, including obtaining appropriate consent, and health system implications. A more in-depth understanding of the barriers associated with implementing genomic newborn screening is critical to the success of GNBS programs, both from a practical perspective and also in order to maintain public trust in an important public health initiative.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"681-691"},"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/4f/7b/pgpm-16-681.PMC10321326.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9805770","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}

{"title":"Role of <i>CYP19A1</i> Loci (rs28757157 and rs3751591) with Ischemic Stroke Risk in the Chinese Han Population.","authors":"Kang Huang,&nbsp;Tianyi Ma,&nbsp;Qiang Li,&nbsp;Zanrui Zhong,&nbsp;Ting Qin,&nbsp;Yilei Zhou,&nbsp;Wei Zhang,&nbsp;Shilin Tang,&nbsp;Jianghua Zhong,&nbsp;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}

{"title":"High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma.","authors":"Xuegang Wang,&nbsp;Weiquan Li,&nbsp;Ning Lou,&nbsp;Weiwei Han,&nbsp;Bo Hai,&nbsp;Wen Xiao,&nbsp;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}

{"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,&nbsp;Rutie Yin,&nbsp;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}

{"title":"Identification and Validation of Ferroptosis-Related Subtypes and a Predictive Signature in Hepatocellular Carcinoma.","authors":"Chunlan Zheng,&nbsp;Yanan Peng,&nbsp;Haizhou Wang,&nbsp;Youwei Wang,&nbsp;Lan Liu,&nbsp;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}