Pharmacogenomics & Personalized Medicine最新文献

{"title":"Novel <i>MYBPC3</i> Mutations in Indian Population with Cardiomyopathies.","authors":"Deepa Selvi Rani,&nbsp;Apoorva Kasala,&nbsp;Perundurai S Dhandapany,&nbsp;Uthiralingam Muthusami,&nbsp;Sreejith Kunnoth,&nbsp;Andiappan Rathinavel,&nbsp;Dharma Rakshak Ayapati,&nbsp;Kumarasamy Thangaraj","doi":"10.2147/PGPM.S407179","DOIUrl":"https://doi.org/10.2147/PGPM.S407179","url":null,"abstract":"<p><strong>Background: </strong>Mutations in Myosin Binding Protein C (<i>MYBPC3</i>) are one of the most frequent causes of cardiomyopathies in the world, but not much data are available in India.</p><p><strong>Methods: </strong>We carried out targeted direct sequencing of <i>MYBPC3 </i>in 115 hypertrophic (HCM) and 127 dilated (DCM) cardiomyopathies against 197 ethnically matched healthy controls from India.</p><p><strong>Results: </strong>We detected 34 single nucleotide variations in <i>MYBPC3</i>, of which 19 were novel. We found a splice site mutation [(IVS6+2T) T>G] and 16 missense mutations in Indian cardiomyopathies [5 in HCM; E258K, T262S, H287L, R408M, V483A: 4 in DCM; T146N, V321L, A392T, E393K and 7 in both HCM and DCM; L104M, V158M, S236G, R272C, T290A, G522E, A626V], but those were absent in 197 normal healthy controls. Interestingly, we found 7 out of 16 missense mutations (V158M, E258K, R272C, A392T, V483A, G522E, and A626V) in <i>MYBPC3</i> were altering the evolutionarily conserved native amino acids, accounted for 8.7% and 6.3% in HCM and DCM, respectively. The bioinformatic tools predicted that those 7 missense mutations were pathogenic. Moreover, the co-segregation of those 7 mutations in families further confirmed their pathogenicity. Remarkably, we also identified compound mutations within the <i>MYBPC3</i> gene of 6 cardiomyopathy patients (5%) with more severe disease phenotype; of which, 3 were HCM (2.6%) [(1. K244K + E258K + (IVS6+2T) T>G); (2. L104M + G522E + A626V); (3. P186P + G522E + A626V]; and 3 were DCM (2.4%) [(1. 5'UTR + A392T; 2. V158M+G522E; and 3.V158M + T262T + A626V].</p><p><strong>Conclusion: </strong>The present comprehensive study on <i>MYBPC3</i> has revealed both single and compound mutations in <i>MYBPC3</i> and their association with disease in Indian Population with Cardiomyopathies. Our findings may perhaps help in initiating diagnostic strategies and eventually recognizing the targets for therapeutic interventions.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"883-893"},"PeriodicalIF":1.9,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/7a/pgpm-16-883.PMC10518145.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154182","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":"Genome-Wide Identification of lncRNA and mRNA for Diagnosing Type 2 Diabetes in Saudi Arabia.","authors":"Sarah Albogami","doi":"10.2147/PGPM.S427977","DOIUrl":"https://doi.org/10.2147/PGPM.S427977","url":null,"abstract":"<p><strong>Purpose: </strong>According to the World Health Organization, Saudi Arabia ranks seventh worldwide in the number of patients with diabetes mellitus. To our knowledge, no research has addressed the potential of noncoding RNA as a diagnostic and/or management biomarker for patients with type 2 diabetes mellitus (T2DM) living in high-altitude areas. This study aimed to identify molecular biomarkers influencing patients with T2DM living in high-altitude areas by analyzing lncRNA and mRNA.</p><p><strong>Patients and methods: </strong>RNA sequencing and bioinformatics analyses were used to identify significantly expressed lncRNAs and mRNAs in T2DM and healthy control groups. Coding potential was analyzed using coding-noncoding indices, the coding potential calculator, and PFAM, and the lncRNA function was predicted using Pearson's correlation. Differentially expressed transcripts between the groups were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify the biological functions of both lncRNAs and mRNAs.</p><p><strong>Results: </strong>We assembled 1766 lncRNAs in the T2DM group, of which 582 were novel. This study identified three lncRNA target genes (<i>KLF2, CREBBP</i>, and <i>REL</i>) and seven mRNAs (<i>PIK3CD, PIK3R5, IL6R, TYK2, ZAP70, LAMTOR4</i>, and <i>SSH2</i>) significantly enriched in important pathways, playing a role in the progression of T2DM.</p><p><strong>Conclusion: </strong>To the best of our knowledge, this comprehensive study is the first to explore the applicability of certain lncRNAs as diagnostic or management biomarkers for T2DM in females in Taif City, Saudi Arabia through the genome-wide identification of lncRNA and mRNA profiling using RNA seq and bioinformatics analysis. Our findings could help in the early diagnosis of T2DM and in designing effective therapeutic targets.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"859-882"},"PeriodicalIF":1.9,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/a0/pgpm-16-859.PMC10508282.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41174231","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":"Chromosomal Copy Number Variation Predicts EGFR-TKI Response and Prognosis for Patients with Non-Small Cell Lung Cancer.","authors":"Haiyan He,&nbsp;Hang Ma,&nbsp;Zhuo Chen,&nbsp;Jingliang Chen,&nbsp;Dandan Wu,&nbsp;Xuedong Lv,&nbsp;Jie Zhu","doi":"10.2147/PGPM.S418320","DOIUrl":"10.2147/PGPM.S418320","url":null,"abstract":"<p><strong>Purpose: </strong>Chromosomal abnormalities represent genomic signatures linked to cancer prognosis and responses to chemotherapy, immunotherapy, and drug resistance. This study aimed to investigate the impact of chromosome copy number variants (CNVs) on the efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC) patients, as well as its prognostic implications for progression-free survival (PFS) and overall survival (OS) in EGFR wild-type patients.</p><p><strong>Methods: </strong>A total of 110 patients with advanced NSCLC were enrolled in this study and categorized into EGFR-mutated and wild-type groups. Utilizing next-generation sequencing (NGS) technology, we assessed 24 genes and chromosome CNVs associated with lung cancer pathways in patients' tissue samples.</p><p><strong>Results: </strong>Within the EGFR-mutated group, patients with a gain in Chr 1p13.3-p13.1 exhibited poor TKI responses, a high relapse rate, and shortened PFS (<i>P</i> = 0.002). Conversely, EGFR-mutated patients with a gain in 14q31.1-q31.3 demonstrated favorable TKI responses and relatively extended PFS (<i>P</i> = 0.005). Among EGFR wild-type patients, the presence of 7q31.1-q31.31 CNV emerged as an independent factor influencing both PFS and OS (<i>P</i> = 0.013, <i>P</i> = 0.004). Notably, patients with a gain in 7q31.1-q31.31 exhibited prolonged PFS and OS. Additionally, independent prognostic significance for OS in EGFR wild-type patients was observed for CNVs in 9q21.31-q22.2 and 11p11.11-q12.1 regions (<i>P</i> = 0.001). Patients with gains in these regions experienced extended OS, while losses were predictive of poorer outcomes.</p><p><strong>Conclusion: </strong>Our results suggested that chromosomal copy number variation is a practical indicator for predicting the response of EGFR-targeted therapy and prognosis for NSCLC patients.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"835-846"},"PeriodicalIF":1.9,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/c9/pgpm-16-835.PMC10505391.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10313102","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 Significance of NAT2 Genetic Variations in Type II Diabetes Mellitus and Lipid Regulation.","authors":"Yazun Jarrar,&nbsp;Sara Abudahab,&nbsp;Ghasaq Abdul-Wahab,&nbsp;Dana Zaiter,&nbsp;Abdalla Madani,&nbsp;Sara J Abaalkhail,&nbsp;Dina Abulebdah,&nbsp;Hussam Alhawari,&nbsp;Rami Musleh,&nbsp;Su-Jun Lee","doi":"10.2147/PGPM.S422495","DOIUrl":"10.2147/PGPM.S422495","url":null,"abstract":"<p><strong>Background: </strong>N-acetyltransferase 2 (NAT2) enzyme is a Phase II drug-metabolizing enzyme that metabolizes different compounds. Genetic variations in <i>NAT2</i> can influence the enzyme's activity and potentially lead to the development of certain diseases.</p><p><strong>Aim: </strong>This study aimed to investigate the association of <i>NAT2</i> variants with the risk of Type II diabetes mellitus (T2DM) and the lipid profile among Jordanian patients.</p><p><strong>Methods: </strong>We sequenced the whole protein-coding region in <i>NAT2</i> using Sanger's method among a sample of 45 Jordanian T2DM patients and 50 control subjects. Moreover, we analyzed the lipid profiles of the patients and examined any potential associations with <i>NAT2</i> variants.</p><p><strong>Results: </strong>This study revealed that the heterozygous <i>NAT2*13 C/T</i> genotype is significantly (<i>P</i> = 0.03) more common among T2DM (44%) than non-T2DM subjects (23.5%). Furthermore, the frequency of homozygous <i>NAT2*13 T/T</i> genotype was found to be significantly higher (<i>P</i> = 0.03) among T2DM patients (26.7%) compared to that of non-T2DM subjects (11%). The heterozygous <i>NAT2*7 G/A</i> genotype was exclusively observed in T2DM patients (11.1%) and absent in the control non-T2DM group. Moreover, among T2DM patients, those with a homozygous <i>NAT2*11</i> T/T genotype exhibited significantly higher levels of triglycerides (381.50 ± 9.19 ng/dL) with a <i>P</i> value of 0.01 compared to those with heterozygous <i>NAT2*11</i> C/T (136.23 ± 51.12 ng/dL) or wild-type <i>NAT2*11</i> C/C (193.65 ± 109.89 ng/dL) genotypes. T2DM patients with homozygous <i>NAT2*12</i> G/G genotype had a significantly (<i>P</i> = 0.04) higher triglyceride levels (275.67 ± 183.42 ng/dL) than the heterozygous <i>NAT2*12 A/G</i> (140.02 ± 49.53 ng/dL) and the wild <i>NAT2*12 A/A</i> (193.65 ± 109.89 ng/dL).</p><p><strong>Conclusion: </strong>The finding in this study suggests that the <i>NAT2</i> gene is a potential biomarker for the development of T2DM and changes in triglyceride levels among Jordanians. However, it is important to note that our sample size was limited; therefore, further clinical studies with a larger cohort are necessary to validate these findings.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"847-857"},"PeriodicalIF":1.9,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/be/pgpm-16-847.PMC10505377.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10313104","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":"PSMC2 is a Novel Prognostic Biomarker and Predicts Immunotherapeutic Responses: From Pancreatic Cancer to Pan-Cancer.","authors":"Wei Huang, Zhengtao Qian, Yuxin Shi, Zheming Zhang, Rui Hou, Jie Mei, Junying Xu, Junli Ding","doi":"10.2147/PGPM.S418533","DOIUrl":"10.2147/PGPM.S418533","url":null,"abstract":"<p><strong>Background: </strong>Proteasome 26S subunit ATPase 2 (PSMC2) is a part of the 19S regulatory complex, which catalyzes the unfolding and transport of substrates into the 20S proteasome. Our previous research demonstrated that PSMC2 participates in the tumorigenesis and progression of pancreatic cancer (PC). However, no systematic analysis has been conducted to conclude its expression pattern and correlation with tumor immunity.</p><p><strong>Aim: </strong>To investigate the expression level of PSMC2 in PC, its prognostic value and its relationship with tumor immunity.</p><p><strong>Methods: </strong>In numerous public and internal cohorts, the expression, prognostic significance, and immunological connections of PSMC2 in PC were investigated. Additionally, using data from The Cancer Genome Atlas (TCGA), a pan-cancer analysis was carried out to examine PSMC2's immunological assocaition, and the predictive power of PSMC2 for immunotherapy was also evaluated in numerous public cohorts.</p><p><strong>Results: </strong>PSMC2 was overexpressed in tumor tissues and linked to unfavorable prognosis in PC. PSMC2 was not only positively correlated with TIICs, also positively correlated with immune checkpoints in PC. In addition to PC, PSMC2 was expected to be an indicator of high immunogenicity in most cancer types. Importantly, PSMC2 could predict the immunotherapeutic responses in various cancer types, including urothelial carcinoma and breast cancer.</p><p><strong>Conclusion: </strong>From PC to pan-cancer analysis, we report that PSMC2 is a novel prognostic biomarker in multiple cancer types. PSMC2 is related to the immuno-hot phenotype and predicts the outcome of immunotherapy. Therefore, the current study emphasizes that cancer patients with high PMSC2 expression should actively receive immunotherapy to improve their prognosis.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"747-758"},"PeriodicalIF":1.8,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/6f/pgpm-16-747.PMC10423611.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10006285","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 of Novel Prognostic Biomarkers That are Associated with Immune Microenvironment Based on GABA-Related Molecular Subtypes in Gastric Cancer.","authors":"Beibei Wang, Linlin Huang, Shanliang Ye, Zhongwen Zheng, Shanying Liao","doi":"10.2147/PGPM.S411862","DOIUrl":"10.2147/PGPM.S411862","url":null,"abstract":"<p><strong>Background: </strong>Gamma-aminobutyric acid (GABA) plays an important role in tumorigenesis and progression. Despite this, the role of Reactome GABA receptor activation (RGRA) on gastric cancer (GC) remains unclear. This study was intended to screen RGRA-related genes in GC and investigate their prognostic value.</p><p><strong>Methods: </strong>GSVA algorithm was used to assess the score of RGRA. GC patients were divided into two subtypes based on the median score of RGRA. GSEA, functional enrichment analysis, and immune infiltration analysis were performed between the two subgroups. Then, differentially expressed analysis, and weighted gene co-expression network analysis (WGCNA) were used to identify RGRA-related genes. The prognosis and expression of core genes were analyzed and validated in the TCGA database, GEO database, and clinical samples. ssGSEA and ESTIMATE algorithms were used to assess the immune cell infiltration in the low- and high-core genes subgroups.</p><p><strong>Results: </strong>High-RGRA subtype had a poor prognosis and activated immune-related pathways, as well as an activated immune microenvironment. ATP1A2 was identified to be the core gene. The expression of ATP1A2 was associated with the overall survival rate and tumor stage, and its expression was down-regulated in GC patients. Furthermore, ATP1A2 expression was positively correlated with the level of immune cells, including B cells, CD8 T cells, cytotoxic cells, DC, eosinophils, macrophages, mast cells, NK cells, and T cells.</p><p><strong>Conclusion: </strong>Two RGRA-related molecular subtypes were identified that could predict the outcome in GC patients. ATP1A2 was a core immunoregulatory gene and was associated with prognosis and immune cell infiltration in GC.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"665-679"},"PeriodicalIF":1.9,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/09/pgpm-16-665.PMC10315139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9792751","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":"Use of Continuous Glucose Monitors to Manage Type 1 Diabetes Mellitus: Progress, Challenges, and Recommendations.","authors":"Jared G Friedman, Zulma Cardona Matos, Emily D Szmuilowicz, Grazia Aleppo","doi":"10.2147/PGPM.S374663","DOIUrl":"10.2147/PGPM.S374663","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"263-276"},"PeriodicalIF":1.9,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/1e/pgpm-16-263.PMC10072139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9625864","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":"Current Understanding of Inherited Modifiers of FVIII Pharmacokinetic Variation.","authors":"Laura L Swystun, David Lillicrap","doi":"10.2147/PGPM.S383221","DOIUrl":"10.2147/PGPM.S383221","url":null,"abstract":"<p><p>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 <i>VWF</i> 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.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"239-252"},"PeriodicalIF":1.8,"publicationDate":"2023-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/1b/pgpm-16-239.PMC10046206.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9230529","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":"Massive Hepatocellular Carcinoma with Situs Inversus Totalis Achieved a Complete Response Following Camrelizumab Plus Apatinib and Combined with Two-Stage Hepatectomy: A Case Report.","authors":"Yining Wu, Shenjian Ou, Xiwen Liao, Chuangye Han, Chengkun Yang, Wei Qin, Yufeng Tan, Quan Lao, Tao Peng, Xinping Ye","doi":"10.2147/PGPM.S376596","DOIUrl":"10.2147/PGPM.S376596","url":null,"abstract":"<p><p>Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Two-stage hepatectomy (TSH) combined with translational therapy for hepatocellular carcinoma (HCC) with SIT has been rarely reported. We report a 41-year-old man with giant hepatocellular carcinoma (71 mm × 55 mm × 51 mm) whose future residual liver (FLR) and standard liver volume (SLV) ratio at first diagnosis was 37.4%. Preoperative volume assessment of portal vein ligation (PVL) revealed inadequate hypertrophy of FLR. After a multidisciplinary group discussion (MDT), the patient decided to follow conversion therapy. Three months later, ratio of the FLR/SLV increased from 37.4% to 71% after operation, which met the surgical requirements. Second hepatectomy, right lobectomy was successful. There was no recurrence after six months of follow-up. In our case, conversion therapy appears to be effective in maintaining residual liver hyperplasia, reducing tumor load, and preventing tumor progression in patients with large HCC during TSH.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"111-120"},"PeriodicalIF":1.8,"publicationDate":"2023-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/45/pgpm-16-111.PMC9921441.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10713044","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":"Nidogen-2 (NID2) is a Key Factor in Collagen Causing Poor Response to Immunotherapy in Melanoma.","authors":"Yan Sha,&nbsp;An-Qi Mao,&nbsp;Yuan-Jie Liu,&nbsp;Jie-Pin Li,&nbsp;Ya-Ting Gong,&nbsp;Dong Xiao,&nbsp;Jun Huang,&nbsp;Yan-Wei Gao,&nbsp;Mu-Yao Wu,&nbsp;Hui Shen","doi":"10.2147/PGPM.S399886","DOIUrl":"https://doi.org/10.2147/PGPM.S399886","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>We clarified the adverse effects of collagen on melanoma patients and identified NID2 as a potential therapeutic target.</p>","PeriodicalId":56015,"journal":{"name":"Pharmacogenomics & Personalized Medicine","volume":"16 ","pages":"153-172"},"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/f4/b8/pgpm-16-153.PMC9994630.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9155229","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}