Cancer Genomics & Proteomics最新文献

{"title":"p21 Protein Outperforms Clinico-pathological Criteria in Predicting Liver Metastases in Pancreatic Endocrine Tumors.","authors":"Aejaz Nasir, Malik K Ahmed, James J Saller, Evita B Henderson-Jackson, Mokenge P Malafa, Timothy J Yeatman, Domenico Coppola","doi":"10.21873/cgp.20402","DOIUrl":"10.21873/cgp.20402","url":null,"abstract":"<p><strong>Background/aim: </strong>P21 is a cyclin-dependent kinase inhibitor regulating the cell cycle as a tumor suppressor. Using a p21 immunohistochemistry (IHC) assay, we compared tumor p21 levels with conventional clinico-pathological criteria in primary pancreatic endocrine tumor subsets with and without liver metastases.</p><p><strong>Materials and methods: </strong>Sections from tissue microarray (TMA) including 13 archival metastatic primary and 18 non-metastatic primary pancreatic endocrine carcinomas/tumors (MP-PECAs/NMP-PETs) were stained with a monoclonal anti-p21^WAFI,CIP primary antibody. Tumor p21 IHCs were scored as the sum of intensity (0-3) and proportion scores (0-5) (Total Allred score: 0-8), and as p21% labelling index in the tumor. ROC curve analysis was used for most optimal p21 score cut-off (4 or >) and Fisher's exact test was used to compare the association among tumor p21 scores, conventional prognostic criteria, and liver metastases.</p><p><strong>Results: </strong>For PET/PECA patients, mean ages were 55.6 years (27-73) and 49.3 years (28-71), M/F ratios were 7/11 and 7/6. Mean p21 labelling index (%) for MP- PECAs was 24% (range=3-63%) vs. 9% for NMP-PETs (range=1-25%) (p=0.022). The mean p21 index in MP-PECAs was significantly higher (24%) as compared to PIs (7%) (p=0.0047). Using a p21 Allred score of ≥4, high p21 IHC score had strong association with the presence of liver metastases (p-value <0.001). High tumor p21 IHC score had a 93% sensitivity, 68% specificity, 78% predictive accuracy, 66% positive, and 94% negative predictive values.</p><p><strong>Conclusion: </strong>In patients with primary PETs, p21 IHC is superior to conventional criteria in predicting presence or absence of liver metastases.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227767","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":"Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in Preclinical <i>In Vivo</i> Models.","authors":"Ulrich H Weidle,&nbsp;Adam Nopora","doi":"10.21873/cgp.20401","DOIUrl":"10.21873/cgp.20401","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) ranges as number two with respect to the incidence of tumors and is associated with a dismal prognosis. The therapeutic efficacy of approved multi-tyrosine kinase inhibitors and checkpoint inhibitors is modest. Therefore, the identification of new therapeutic targets and entities is of paramount importance. We searched the literature for up-regulated circular RNAs (circRNAs) which mediate efficacy in preclinical in vivo models of HCC. Our search resulted in 14 circRNAs which up-regulate plasma membrane transmembrane receptors, while 5 circRNAs induced secreted proteins. Two circRNAs facilitated replication of Hepatitis B or C viruses. Three circRNAs up-regulated high mobility group proteins. Six circRNAs regulated components of the ubiquitin system. Seven circRNAs induced GTPases of the family of ras-associated binding proteins (RABs). Three circRNAs induced redox-related proteins, eight of them up-regulated metabolic enzymes and nine circRNAs induced signaling-related proteins. The identified circRNAs up-regulate the corresponding targets by sponging microRNAs. Identified circRNAs and their targets have to be validated by standard criteria of preclinical drug development. Identified targets can potentially be inhibited by small molecules or antibody-based moieties and circRNAs can be inhibited by small-interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) for therapeutic purposes.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227754","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":"Hsa_circ_0079557 Promotes the Proliferation of Colorectal Cancer Cells Through the hsa_circ_0079557/miR-502-5p/CCND1 Axis.","authors":"Chao Yu, Xue Huang, Renli Huang, Peiqi Wang, Zongda Cai, Zeyi Guo, Qingnan Lan, Haodi Cao, Jinlong Yu","doi":"10.21873/cgp.20406","DOIUrl":"10.21873/cgp.20406","url":null,"abstract":"<p><strong>Background/aim: </strong>Recent studies have demonstrated the crucial regulatory roles of circular RNAs (circRNAs) in cancer initiation and progression. The sponge mechanism of circRNAs has been shown to be widely active in various types of tumors. However, many circRNAs still have not been verified to function through this mechanism. This study aimed to investigate the regulatory mechanism of hsa_circ_0079557 in colorectal cancer (CRC) and its role in CRC progression.</p><p><strong>Materials and methods: </strong>Raw gene expression profile datasets were downloaded from Gene Expression Omnibus (GEO) and combined to form a new dataset. Hsa_circ_0079557 was found to be highly expressed in CRC. Its role was evaluated in vitro and in vivo through a series of experiments, including quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, colony formation, cell counting kit-8 (CCK-8), transwell assays, scratch wound healing assays, nude mice experiments, and immunohistochemistry (IHC). The association between hsa_circ_0079557 and the identified target microRNAs (miRNA) was confirmed through fluorescence in situ hybridization (FISH) and dual-luciferase reporter assays. The downstream target proteins were predicted using the web-based tool \"TargetScan,\" and their expressions were determined using Western blot (WB).</p><p><strong>Results: </strong>Hsa_circ_0079557 was found to be relatively up-regulated in CRC tissues and cell lines. Suppression of hsa_circ_0079557 expression inhibited cell proliferation in vitro and in vivo. Additionally, hsa_circ_0079557 acted as a \"molecular sponge\" for miR-502-5p, up-regulating the expression of Cyclin D1 (CCND1).</p><p><strong>Conclusion: </strong>In this study, we identify a highly expressed circRNA in CRC and propose a novel pathway of hsa_circ_0079557/miR-502-5p/CCND1 in CRC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227755","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":"Pathogenetic Dichotomy in Angioleiomyoma.","authors":"Ioannis Panagopoulos,&nbsp;Kristin Andersen,&nbsp;Marta Brunetti,&nbsp;Ludmila Gorunova,&nbsp;Ilyá Kostolomov,&nbsp;Wanja Kildal,&nbsp;Hanne Regine Hognestad,&nbsp;Ingvild Lobmaier,&nbsp;Francesca Micci,&nbsp;Sverre Heim","doi":"10.21873/cgp.20405","DOIUrl":"10.21873/cgp.20405","url":null,"abstract":"<p><strong>Background/aim: </strong>Angioleiomyoma is a benign tumor, occurs at any age, and arises most frequently in the lower extremities. Genetic information on angioleiomyomas is restricted to six reported abnormal karyotypes, losses in chromosome 22 and gains in Xq found by comparative genomic hybridization, and mutation analysis of notch receptor 2 (NOTCH2), NOTCH3, platelet-derived growth factor receptor beta (PDGFRB), and mediator complex subunit 12 (MED12) in a few tumors. Herein, we report the genetic findings in another three angioleiomyomas.</p><p><strong>Materials and methods: </strong>The tumors were examined using G-banding and karyotyping, RNA sequencing, reverse transcription-polymerase chain reaction, Sanger sequencing, and expression analysis.</p><p><strong>Results: </strong>The first tumor carried a t(4;5)(p12;q32) translocation resulting in fusion of the cardiac mesoderm enhancer-associated non-coding RNA (CARMN in 5q32) with the TXK tyrosine kinase gene (TXK in 4p12) leading to overexpression of TXK. To our knowledge, this is the first time that a recurrent chromosome translocation and its resulting fusion gene have been described in angioleiomyomas. The second tumor carried a four-way translocation, t(X;3;4;16)(q22;p11;q11;p13) which fused the myosin heavy chain 11 gene (MYH11 in 16p13) with intergenic sequences from Xq22 that mapped a few kilobase pairs distal to the insulin receptor substrate 4 gene (IRS4), resulting in enhanced IRS4 expression. The third angioleiomyoma carried another rearrangement of chromosome band Xq22, t(X;9)(q22;q32), as the sole cytogenetic aberration, but no material was available for further molecular investigation.</p><p><strong>Conclusion: </strong>Our data, together with previously reported abnormal karyotypes in angioleiomyomas, show the presence of two recurrent genetic pathways in this tumor type: The first is characterized by presence of the translocation t(4;5)(p12;q32), which generates a CARMN::TXK chimera. The second is recurrent rearrangement of Xq22 resulting in overexpression of IRS4.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227768","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":"SUV39H1 Expression as a Guideline for Omitting Radiotherapy in Lymph Node-positive Triple-negative Breast Cancer Patients.","authors":"Wei-Lun Huang,&nbsp;Chi-Wen Luo,&nbsp;Huei-Shan Lin,&nbsp;Chao-Ming Hung,&nbsp;Fang-Ming Chen,&nbsp;Sin-Hua Moi,&nbsp;Mei-Ren Pan","doi":"10.21873/cgp.20407","DOIUrl":"10.21873/cgp.20407","url":null,"abstract":"<p><strong>Background/aim: </strong>The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs.</p><p><strong>Materials and methods: </strong>Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses.</p><p><strong>Results: </strong>The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basal-like 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel.</p><p><strong>Conclusion: </strong>Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227771","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":"Using Comparative Proteomics to Identify Protein Signatures in Clear Cell Renal Cell Carcinoma.","authors":"Juhee Park,&nbsp;Eun Hye Lee,&nbsp;Hyunchae Sim,&nbsp;Ann-Yae Na,&nbsp;So Young Choi,&nbsp;Jae-Wook Chung,&nbsp;Yun-Sok Ha,&nbsp;Tae Gyun Kwon,&nbsp;Sangkyu Lee,&nbsp;Jun Nyung Lee","doi":"10.21873/cgp.20408","DOIUrl":"10.21873/cgp.20408","url":null,"abstract":"<p><strong>Background/aim: </strong>Renal cell carcinoma (RCC) is one of the most commonly diagnosed cancers in the world. Approximately 25-30% of patients identified with initial kidney cancer will have metastasized tumors, thus 5-year survival rates for these patients are poor. Therefore, biomarker research is required to identify and predict molecular signatures in RCC.</p><p><strong>Materials and methods: </strong>To address this, we used a mass spectrometry (MS)-based proteomics approach to identify proteins related to clear cell RCC (ccRCC) tissues from patients with T1G2, T1G3, T3G2, T3G3, and metastatic RCC (mRCC) stages.</p><p><strong>Results: </strong>We identified and quantified 2,608 and 2,463 proteins, respectively, in ccRCC tissue and identified 1,449 differentially expressed proteins (DEPs). Bioinformatics analysis revealed that serpin family A member 3 (SERPINA3) qualified as biomarker for ccRCC progression. Using indirect enzyme-linked immunosorbent assay (ELISA), immunoblotting, and immunohistochemistry assays it was found that SERPINA3 expression levels in ccRCC tissues were much higher in stages before metastasis.</p><p><strong>Conclusion: </strong>Comparative proteomics analysis of ccRCC tissues provided new evidence of SERPINA3 association with ccRCC progression.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227772","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":"Inhibition of Increased Invasiveness of Breast Cancer Cells With Acquired Tamoxifen Resistance by Suppression of CYR61.","authors":"Gerd Bauerschmitz,&nbsp;Silke Hüchel,&nbsp;Julia Gallwas,&nbsp;Carsten Gründker","doi":"10.21873/cgp.20403","DOIUrl":"10.21873/cgp.20403","url":null,"abstract":"<p><strong>Background/aim: </strong>Hormone sensitivity-targeted therapy with selective estrogen receptor modulators (SERMs), such as 4-hydroxytamoxifen (4-OHT), is the mainstay of treatment for breast cancers (BCs) that express estrogen receptor α (ERα). However, development of resistance limits this therapy approach. The question arises whether changes associated with 4-OHT resistance could be exploited therapeutically.</p><p><strong>Materials and methods: </strong>First, 4-OHT-resistant sublines of ERα-positive breast carcinoma cell lines MCF-7 and T47D were generated. Viability was assessed by the Alamar Blue assay. Cell invasion was quantified in modified Boyden chambers with Matrigel. Changes in expression of CYR61, S100A4, and ERα were examined by RT-qPCR. Expression of CYR61 was suppressed by transient gene silencing using siRNA. Successful suppression was verified by western blot. Efficacy of 4-OHT treatment was analyzed by quantification of viability using Alamar Blue assay. Correlation of CYR61 levels in patients with luminal A BC to distant metastases-free survival was determined by Kaplan-Meier analysis.</p><p><strong>Results: </strong>ERα-positive MCF-7 and T47D BC cells exhibit an extremely weak invasion rate. Acquired tamoxifen resistance significantly increased the invasive behavior of both tamoxifen-resistant MCF-7-TR and T47D-TR sublines. In addition, expression of CYR61 and S100A4 showed significantly increased levels, whereas expression of ERα was decreased. Suppression of CYR61 expression resulted in a significant decreased invasion rate. In addition, expression of S100A4 was reduced, whereas expression of ERα was increased. Furthermore, suppression of CYR61 resulted in re-sensitization to 4-OHT. High CYR61 levels in patients with luminal A BC resulted in reduced distant metastases-free survival.</p><p><strong>Conclusion: </strong>The prometastatic factor CYR61 appears to play an important role in the increased invasiveness of tamoxifen-resistant ERα-positive BC cells. Its suppression leads to a lower invasion rate. Given the few therapeutic options available for tamoxifen-resistant BC, therapy that reduces CYR61 may improve its treatability in future.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227756","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":"Molecular Characteristics and Therapeutic Vulnerabilities of Claudin-low Breast Cancers Derived from Cell Line Models.","authors":"Ioannis A Voutsadakis","doi":"10.21873/cgp.20404","DOIUrl":"10.21873/cgp.20404","url":null,"abstract":"<p><strong>Background/aim: </strong>Breast cancers constitute heterogeneous tumor groups and their categorization in subtypes based on the expression of the estrogen (ER), progesterone (PR) and HER2 receptors has advanced therapeutics. Claudin-low breast cancer has been proposed as an additional subtype which is mostly ER, PR and HER2 negative, but its identification has not led to corresponding specific treatments yet.</p><p><strong>Materials and methods: </strong>Breast cancer cell lines from the Cancer Cell Line Encyclopedia (CCLE) were assessed for mRNA suppression of claudins and mRNA expression of ER and ERBB2 (the gene encoding HER2). The set of identified claudin-low cell lines were compared with representative ER-/ERBB2- cell lines for associated molecular alterations, gene dependencies through CRISPR and microRNA arrays and in vitro drug sensitivities using the Genomics of Drug Sensitivity in Cancer (GDSC) project.</p><p><strong>Results: </strong>Claudin-low cell lines display up-regulation of mRNA expression of epithelial to mesenchymal transition (EMT) regulators. Methylation sensitive genes are down-regulated in claudin-low lines compared with other cell lines, without associated up-regulation of DNA methyltransferases. Dependency screen microarrays reveal dependencies of claudin-low cell lines on components of the cytoskeleton but no consistent dependencies in known oncogenes or tumor suppressors. Potential drug sensitivities revealed in the drug screens included sensitivities to WNT pathway modulators, tyrosine kinase cascade inhibitors and BET inhibitors. On the other hand, claudin-low cell lines showed resistance to deacetylase inhibitors.</p><p><strong>Conclusion: </strong>Claudin-low cell line models duplicate features of claudin-low breast cancers and may serve as guides for identification of drugs worth exploring for further development.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227757","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":"Risk Stratification by Tissue <i>GAD1</i> Expression Level in Curatively Resected Esophageal Squamous Cell Carcinoma.","authors":"Takayoshi Kishida,&nbsp;Mitsuro Kanda,&nbsp;Yusuke Sato,&nbsp;Dai Shimizu,&nbsp;Yoshikuni Inokawa,&nbsp;Norifumi Hattori,&nbsp;Masamichi Hayashi,&nbsp;Chie Tanaka,&nbsp;Goro Nakayama,&nbsp;Yasuhiro Kodera","doi":"10.21873/cgp.20410","DOIUrl":"10.21873/cgp.20410","url":null,"abstract":"<p><strong>Background/aim: </strong>To improve patient management, new biomarkers are required that stratify prognosis. Here we focused on glutamic acid decarboxylase 1 (GAD1), which is associated with proliferation of lung cancer cells, and investigated its expression and function in esophageal squamous cell carcinoma (ESCC).</p><p><strong>Materials and methods: </strong>We evaluated changes in the proliferative potential of ESCC cell lines using small interfering RNA-mediated GAD1 knockdown techniques. We analyzed GAD1 protein expression using a tissue microarray (TMA) and measured GAD1 mRNA expression to evaluate correlations between the expression level of each tissue and postoperative outcomes of two independent cohorts (the TMA and mRNA cohorts) of patients who underwent radical esophagectomy.</p><p><strong>Results: </strong>GAD1 knockdown reduced cell proliferation. In the TMA cohort, high GAD1 expression significantly correlated with lymph node metastasis and advanced stage. Disease-free survival was significantly shorter in the group with high GAD1 expression, as was overall survival. Multivariate analysis of overall survival showed that positivity for GAD1 was an independent prognostic factor for poor survival. In the mRNA cohort, GAD1 mRNA expression in ESCC tissues was significantly up-regulated compared with that in adjacent noncancerous mucosal tissues. When patients were divided into high- and low-expression groups according to the median GAD1 mRNA expression level in ESCC tissues, overall survival was significantly shortened in the high GAD1 expression group. The incidence of initial hematogenous recurrence was significantly higher in the group with high GAD1 expression.</p><p><strong>Conclusion: </strong>GAD1 expression mediates the proliferative potential of ESCC cells, and a high level may serve as a useful prognostic biomarker for patients with ESCC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227770","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":"Clinicopathological and Prognostic Values of Telomerase Reverse Transcriptase (<i>TERT</i>) Promoter Mutations in Ovarian Clear Cell Carcinoma for Predicting Tumor Recurrence, Platinum Resistance and Survival.","authors":"Hyunwoo Yoo, Hyun-Soo Kim","doi":"10.21873/cgp.20411","DOIUrl":"10.21873/cgp.20411","url":null,"abstract":"<p><strong>Background/aim: </strong>A small subset of patients with ovarian clear cell carcinoma (OCCC) harbors telomerase reverse transcriptase promoter (TERTp) mutations. We aimed to analyze the clinicopathological and molecular characteristics of TERTp-mutant OCCC and investigate whether TERTp mutations are associated with the clinicopathological characteristics and outcomes of patients with OCCC.</p><p><strong>Patients and methods: </strong>We included 11 OCCC cases in our study. Targeted sequencing was performed with a thorough review of pathology slides and electronic medical records.</p><p><strong>Results: </strong>Eleven OCCCs harbored two hotspot TERTp mutations: c.1-146C>T (6/11) and c.1-124C>T (5/11). All patients (11/11) who underwent postoperative adjuvant chemotherapy experienced tumor recurrence, and eight of them were classified as platinum-resistant. TERTp-mutant OCCC showed significantly higher frequencies of postoperative recurrence and relapse within six months of chemotherapy. TERTp mutations significantly predicted disease-free survival (DFS) in patients with OCCC.</p><p><strong>Conclusion: </strong>We demonstrate that TERTp mutations have significant prognostic value for predicting tumor recurrence, platinum resistance, and worse DFS in patients with OCCC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227753","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}