Cancer Genomics & Proteomics最新文献

{"title":"Prostate Cancer: De-regulated Circular RNAs With Efficacy in Preclinical <i>In Vivo</i> Models.","authors":"Ulrich H Weidle, Fabian Birzele","doi":"10.21873/cgp.20494","DOIUrl":"10.21873/cgp.20494","url":null,"abstract":"<p><p>Therapy resistance, including castration-resistance and metastasis, remains a major hurdle in the treatment of prostate cancer. In order to identify novel therapeutic targets and treatment modalities for prostate cancer, we conducted a comprehensive literature search on PubMed to identify de-regulated circular RNAs that influence treatment efficacy in preclinical prostate cancer-related <i>in vivo</i> models. Our analysis identified 49 circular RNAs associated with various processes, including treatment resistance, transmembrane and secreted proteins, transcription factors, signaling cascades, human antigen R, nuclear receptor binding, ubiquitination, metabolism, epigenetics and other target categories. The identified targets and circular RNAs can be further scrutinized through target validation approaches. Down-regulated circular RNAs are candidates for reconstitution therapy, while up-regulated RNAs can be inhibited using small interfering RNA (siRNA), antisense oligonucleotides (ASO) or clustered regularly interspaced short palindromic repeats/CRISPR associated (CRISPR-CAS)-related approaches.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"136-165"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490844","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":"Correlation of GD2 Biosynthesis Enzymes With Cancer Stem Cell Markers in Human Breast Cancer.","authors":"Niamh S O'Neill, Mariam Rizk, Amber X Li, Tracey A Martin, Wen G Jiang, Kefah Mokbel","doi":"10.21873/cgp.20498","DOIUrl":"10.21873/cgp.20498","url":null,"abstract":"<p><strong>Background/aim: </strong>The disialoganglioside GD2 has been shown to promote cell proliferation, migration, tumor and metastasis through specific signaling pathways in tumor cells originating from the neuroectoderm, including melanomas, neuroblastomas, glioblastomas, and breast carcinomas. GD2 has therefore emerged as a potential diagnostic biomarker in early malignancy as evidenced by the high specificity of its expression in tumor cells. Furthermore, recent findings show that GD2 might also act as a novel cancer stem cell (CSC) marker. Our study aimed to investigate the relationship between GD2 and 34 recognized CSC markers in human breast cancer.</p><p><strong>Materials and methods: </strong>We analyzed the relationship between the mRNA expression profiles of three key enzymes involved in the biosynthesis of GD2 - B4GalT5, B4GALNT1, and ST8SIA1 - and 34 CSC markers in 91 human breast cancer tissue samples.</p><p><strong>Results: </strong>All three enzymes had positive and statistically significant correlation between each other with <i>p</i><0.0001. Furthermore, each enzyme was found to have highly significant correlations with 15 CSC markers associated with aggressive cancer behavior: BMI1, CX43, ALCAM (CD166), Podoplanin, CD29, CD24, CD49f, IL8RA, NGFR, hTERT, Nestin, OCT4, CTBP, PSCA and Myc.</p><p><strong>Conclusion: </strong>These findings lend further support to the growing evidence that GD2 is a potential biomarker of CSCs and epithelial-mesenchymal transition (EMT) in human breast cancer that can be amenable to therapeutic targeting.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"231-246"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490817","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":"Integrated Pharmacogenetic Signature for the Prediction of Prostatic Neoplasms in Men With Metabolic Disorders.","authors":"Maria Pagoni, Vasileios L Zogopoulos, Stavros Kontogiannis, Annia Tsolakou, Vassilios Zoumpourlis, George Th Tsangaris, Eleftherios Fokaefs, Ioannis Michalopoulos, Aristidis M Tsatsakis, Nikolaos Drakoulis","doi":"10.21873/cgp.20502","DOIUrl":"10.21873/cgp.20502","url":null,"abstract":"<p><strong>Background/aim: </strong>Oncogenic processes are delineated by metabolic dysregulation. Drug likeness is pharmacokinetically tested through the CYP450 enzymatic system, whose genetic aberrations under epigenetic stress could shift male organisms into prostate cancer pathways. Our objective was to predict the susceptibility to prostate neoplasia, focused on benign prostatic hyperplasia (BPH) and prostate cancer (PCa), based on the pharmacoepigenetic and the metabolic profile of Caucasians.</p><p><strong>Materials and methods: </strong>Two independent cohorts of 47,389 individuals in total were assessed to find risk associations of CYP450 genes with prostatic neoplasia. The metabolic profile of the first cohort was statistically evaluated and frequencies of absorption-distribution-metabolism-excretion-toxicity (ADMET) properties were calculated. Prediction of miRNA pharmacoepigenetic targeting was performed.</p><p><strong>Results: </strong>We found that prostate cancer and benign prostatic hyperplasia patients of the first cohort shared common cardiometabolic trends. Drug classes C08CA, C09AA, C09CA, C10AA, C10AX of the cardiovascular, and G04CA, G04CB of the genitourinary systems, were associated with increased prostate cancer risk, while C03CA and N06AB of the cardiovascular and nervous systems were associated with low-risk for PCa. CYP3A4*1B was the most related pharmacogenetic polymorphism associated with prostate cancer susceptibility. miRNA-200c-3p and miRNA-27b-3p seem to be associated with CYP3A4 targeting and prostate cancer predisposition. Metabolomic analysis indicated that 11β-OHT, 2β-OHT, 15β-OHT, 2α-OHT and 6β-OHT had a high risk, and 16α-OHT, and 16β-OHT had an intermediate disease-risk.</p><p><strong>Conclusion: </strong>These findings constitute a novel integrated signature for prostate cancer susceptibility. Further studies are required to assess their predictive value more fully.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"285-305"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490820","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":"<i>SPOCD1</i> Enhances Cancer Cell Activities and Serves as a Prognosticator in Esophageal Squamous Cell Carcinoma.","authors":"Tuvshin Bayasgalan, Mitsuro Kanda, Yusuke Sato, Haote Zhu, Mohammad Hussain Hamrah, Flor Esther Garza Martinez, Takahiro Shinozuka, Yuki Ito, Masahiro Sasahara, Dai Shimizu, Shinichi Umeda, Yoshikuni Inokawa, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Yasuhiro Kodera","doi":"10.21873/cgp.20503","DOIUrl":"10.21873/cgp.20503","url":null,"abstract":"<p><strong>Background/aim: </strong>Comprehensive transcriptome analysis has revealed SPOC Domain Containing 1 (SPOCD1) as a potential biomarker for esophageal squamous cell carcinoma (ESCC). However, the expression and oncological roles of SPOCD1 in ESCC remains underexplored. We aimed to evaluate the role of SPOCD1 in oncogenesis and prognosis of ESCC <i>in vitro</i> and <i>in vivo</i>Materials and Methods: The Cancer Cell Line Encyclopedia (CCLE) database was utilized to evaluate correlations between SPOCD1 expression and oncogenes in ESCC. mRNA and protein levels were measured by qRT-PCR and Simple Western assays, respectively. siRNA-mediated knockdown and overexpression experiments assessed the effects of SPOCD1 expression on proliferation, migration, and invasion of ESCC cell lines. <i>In vivo</i>, siRNA knockdown effects on tumor growth were tested in mouse xenograft models. SPOCD1 mRNA levels in 164 resected tissues were correlated with clinicopathological parameters and survival, while a cohort of 177 patients was analyzed for protein expression and survival.</p><p><strong>Results: </strong>SPOCD1 mRNA expression varied widely among ESCC cell lines and correlated with epithelial-mesenchymal transition-related genes. Knockdown significantly suppressed proliferation, migration, and invasion (<i>p</i><0.001), while overexpression increased proliferation (<i>p</i><0.001). <i>In vivo</i>, siRNA knockdown reduced tumor growth compared to both si-control (<i>p</i>=0.005) and untransfected groups (<i>p</i><0.001). High SPOCD1 mRNA expression was linked to poor disease-specific survival (<i>p</i>=0.009, HR=1.965, 95% CI=1.187-3.252) and disease-free survival (<i>p</i>=0.047, HR=1.602, 95% CI=1.007-2.549). Similarly, elevated protein levels were associated with unfavorable disease-specific (<i>p</i>=0.013, HR=1.860, 95% CI=1.137-3.041) and disease-free survival (<i>p</i>=0.032, HR=1.618, 95% CI=1.042-2.513).</p><p><strong>Conclusion: </strong>SPOCD1 expression correlates with the aggressiveness of ESCC cells, and its expression levels in tumor tissues may serve as a prognostic factor for ESCC patients.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"306-325"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490813","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":"Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression to Breast Cancer in African American Women.","authors":"Sylvia Dasi, Tammey J Naab, Bernard Kwabi-Addo, Victor Apprey, Desta Beyene, Robert L Dewitty, Steven Nagel, Robin Williams, Kelly Bolden, Andrea Hayes-Dixon, Babak Shokrani, Delisha A Stewart, Olakunle O Kassim, Robert L Copeland, Yasmine M Kanaan","doi":"10.21873/cgp.20497","DOIUrl":"10.21873/cgp.20497","url":null,"abstract":"<p><strong>Background/aim: </strong>Methylation in the estrogen receptor alpha (ESRα) promoter is an epigenetic abnormality associated with breast cancer (BCa), whereas hypermethylation results in the loss of ER expression.</p><p><strong>Materials and methods: </strong>Pyrosequencing was used to investigate a potential link between aberrant methylation in the P0/P1 promoters of ESRα and the risk of progression of benign fibrocystic and fibroadenoma tumors to BCa.</p><p><strong>Results: </strong>Results showed a significantly elevated level of DNA methylation in ESRα P1 promoter (<i>p</i>=0.0001) in fibroadenoma compared to ER-negative BCa tumors and a two-fold increased ESRα expression in fibrocystic and fibroadenoma benign tissues. In addition, methylation levels of HIN-1 and RASSF1A promoters were elevated in ER-positive compared to ER-negative BCa (<i>p</i>-value<0.04). ANOVA Mixed Model revealed significantly higher methylation levels in the promoter of RASSF1A for fibroadenoma and ER-positive BCa (<i>p</i>=0.004) compared to ER-negative BCa. Tumors with unclassified molecular subtypes (ER-positive, PR-negative, HER2-negative) had elevated levels of methylation (<i>p</i>=0.046) in the P0 promoter compared with luminal B (ER-positive, PR-positive, HER2-positive) tumors. Grade 3 tumors showed a borderline association with ESRα P1 promoter methylation when compared with grade 2 tumors (<i>p</i>=0.056).</p><p><strong>Conclusion: </strong>ESRα P0 promoter hypermethylation may occur in the early stages of breast carcinogenesis, while P1 promoter methylation appears in later stages with a poor prognosis. Therefore, methylation of the ESRα promoter and other tumor-related genes could serve as a potential biomarker for predicting fibroadenoma progression risk to BCa.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"208-230"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490843","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":"Significant Association of Matrix Metalloproteinase-9 Polymorphisms With Triple Negative Breast Cancer Risk.","authors":"Chih-Chiang Hung, Yun-Chi Wang, Hou-Yu Shih, Chia-Hua Liu, Jie-Long He, Jaw-Chyun Chen, Wen-Shin Chang, Chen-Hsien Su, DA-Tian Bau, Chia-Wen Tsai","doi":"10.21873/cgp.20500","DOIUrl":"10.21873/cgp.20500","url":null,"abstract":"<p><strong>Background/aim: </strong>Matrix metalloproteinase-9 (MMP-9) has been associated with the development and progression of breast cancer (BCa). However, the relationship between MMP-9 genetic variants and BCa susceptibility remains contentious and inconclusive. This study aimed to evaluate the association of MMP-9 rs3918242 promoter polymorphisms with BCa, with a particular focus on the risk of triple-negative breast cancer (TNBC).</p><p><strong>Materials and methods: </strong>A case-control study was conducted involving 1,232 BCa patients and 1,232 healthy controls. The MMP-9 rs3918242 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.</p><p><strong>Results: </strong>The genotype distribution of MMP-9 rs3918242 among the control group adhered to Hardy-Weinberg equilibrium (<i>p</i>=0.3265). No statistically significant differences were observed in the genotype frequencies between BCa cases and controls (p for trend=0.2555). Although the homozygous variant genotype (TT) showed a potential risk-increasing effect, this was not statistically significant [odds ratio (OR)=1.43, 95% confidence interval (CI)=0.88-2.36, <i>p</i>=0.1869]. Similarly, allele frequency analysis indicated no significant association between the variant T allele and overall BCa risk (OR=1.13, 95%CI=0.97-1.33, <i>p</i>=0.1265). Additionally, no interaction was detected between MMP-9 rs3918242 genotypes and the age of BCa onset (both p>0.05). Notably, the TT genotype of MMP-9 rs3918242 was significantly associated with an increased risk of TNBC (OR=2.49, 95%CI=1.32-4.72, <i>p</i>=0.0072).</p><p><strong>Conclusion: </strong>The MMP-9 rs3918242 TT genotype may serve as a potential predictive biomarker for TNBC in the Taiwanese population.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"258-270"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490845","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 Characteristics and Chemosensitivity in Germline TP53 Pathogenic Variant Cases Identified by Cancer Genomic Testing.","authors":"Yosuke Saito, Yuki Hoshi, Masamichi Sato, Manabu Seino, Norikazu Watanabe, Masaaki Kawai, Shuhei Suzuki","doi":"10.21873/cgp.20506","DOIUrl":"10.21873/cgp.20506","url":null,"abstract":"<p><strong>Background/aim: </strong>The widespread implementation of cancer genomic profiling (CGP) has led to an increase in the detection of germline TP53 pathogenic variants (gTP53v) in patients who do not meet the classical Li-Fraumeni syndrome (LFS) criteria. The present study aimed to characterize the clinical features and treatment outcomes of gTP53v cases identified through routine CGP testing.</p><p><strong>Patients and methods: </strong>We conducted a retrospective analysis of 43 patients with gTP53v identified through CGP testing between June 2019 and August 2024. Clinical characteristics, molecular features, and treatment outcomes were analyzed and compared with TP53 wild-type cases from the same database (n=6,515).</p><p><strong>Results: </strong>The median age at diagnosis was 38 years (range=1-83 years), with 58.1% of cases presenting with non-core LFS tumors. A genomic analysis revealed diverse variant types (missense: 32, frameshift: 8, and nonsense: 3) with variant allele frequencies ranging between 0.10 and 0.696. Among 37 patients who received first-line chemotherapy, the objective response rate was 62%, which was significantly higher than in TP53 wild-type cases (32%, <i>p</i>=0.02). Complete responses were observed in six patients and partial responses in 14.</p><p><strong>Conclusion: </strong>The present results suggest that gTP53v carriers identified through CGP represent a broader clinical spectrum than classical LFS, while demonstrating potentially favorable treatment outcomes. These results challenge traditional paradigms and emphasize the need for individualized approaches to patient care, particularly in cases with atypical presentations requiring the careful interpretation of mosaicism, de novo mutations, and clonal hematopoiesis.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"354-362"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490816","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":"The WASP/WAVE Protein Family in Breast Cancer and Their Role in the Metastatic Cascade.","authors":"Rhiannon Yannan Yu, Wen G Jiang, Tracey A Martin","doi":"10.21873/cgp.20495","DOIUrl":"10.21873/cgp.20495","url":null,"abstract":"<p><p>The Wiskott-Aldrich syndrome protein (WASP) and the WASP family verprolin-homologous protein (WAVE) family are essential molecules that connect GTPases to the actin cytoskeleton, thereby controlling actin polymerisation through the actin-related protein 2/3 complex. This control is crucial for forming actin-based membrane protrusions necessary for cell migration and invasion. The elevated expression of WASP/WAVE proteins in invasive breast cancer cells highlights their significant role in promoting cell motility and invasion. This review summarises the discovery, structural properties, and activation mechanisms of WASP/WAVE proteins, focuses on the contribution of the WASP/WAVE family to breast cancer invasion and migration, particularly synthesises the results of nearly a decade of research in this field since 2015. By exploring promising therapeutic strategies for breast cancer, including small molecule inhibitors and biological agents, this review stresses the potential for developing anticancer drugs that target the WASP/WAVE family and associated pathways, intending to improve the prognosis for patients with metastatic breast cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"166-187"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490846","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":"Characterization of the Genomic Landscape in HPV-positive Cervical and Head and Neck Squamous Cell Carcinomas by Whole Genome Next Generation Sequencing.","authors":"Jianlan Ren, Nian Ma, Tyler Seckar, Sheynaz Bassa, Nicola Zetola, Surbhi Grover, Zhi Wei, Erle Robertson","doi":"10.21873/cgp.20496","DOIUrl":"10.21873/cgp.20496","url":null,"abstract":"<p><strong>Background/aim: </strong>In this study, we provide a comprehensive characterization of HPV-positive primary cervical cancers (CC) and HPV-positive head and neck squamous cell carcinomas (HNSCC) through whole genome next-generation sequencing. Human papillomavirus (HPV) infection, recognized as a definitive human carcinogen, is increasingly acknowledged for its role in development of human cancers. HPV-driven cervical cancers are among the leading causes of cancer-related deaths worldwide, while HPV-driven head and neck cancers exhibit distinct biological and clinical characteristics. Recent data has provided convincing evidence that HPV-related cervical cancer, like HPV head and neck cancer also predict better outcomes, with viral integration patterns further predicting disease related outcomes.</p><p><strong>Materials and methods: </strong>We designed an experimental study that encompasses four pairs of HPV-positive patient samples with controls, utilizing state-of-the-art Next Generation Sequencing (NGS) technology including whole genome sequencing, transcriptome sequencing and virus integration.</p><p><strong>Results: </strong>Multiple mutated genes, including TTN, COL6A3, and FLNA, were identified shared between CC and HNSCC. Additionally, we observed a notable proportion of pathways affected by oncogenic alterations, particularly in the RTK-RAS and NOTCH pathways, in both CC and HNSCC. Furthermore, we discovered a shared down-regulation of the Hedgehog signaling pathway based on transcriptome expression analysis in KEGG. We also identified RUNX2 and TFPI as sites of virus integration, and upstream as well as downstream pathway modulators, and represent potential targets for therapeutic interventions.</p><p><strong>Conclusion: </strong>Overall, this study showed a thorough comparison between CC and HNSCC from multiple aspects, including gene variations, oncogenic pathways, KEGG enrichment and virus integration sites. However, further studies, which involve larger patient cohorts should be undertaken to further support these findings.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"188-207"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490815","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":"Accumulating Genetic Mutations from Primary to Secondary Biliary Tract Cancers: Analysis of Four Patients With Metachronous Biliary Tract Cancer Using Comprehensive Genomic Profiling.","authors":"Toshio Kokuryo, Yoshio Koike, Junpei Yamaguchi, Masaki Sunagawa, Taisuke Baba, Nobuyuki Watanabe, Shunsuke Onoe, Takashi Mizuno, Tomoki Ebata","doi":"10.21873/cgp.20505","DOIUrl":"10.21873/cgp.20505","url":null,"abstract":"<p><strong>Background/aim: </strong>Metachronous biliary tract cancer (BTC) is a rare occurrence after curative resection of primary BTC. The genetic alterations and pathogenesis associated with metachronous BTC remain poorly understood.</p><p><strong>Patients and methods: </strong>We analyzed four patients with metachronous BTC who underwent resection at the Nagoya University Hospital between 2010 and 2024. Gene panel examination was performed on both primary and secondary tumors using next-generation sequencing.</p><p><strong>Results: </strong>The median interval between resection of the primary tumor and diagnosis of metachronous BTC was 24 months. Genetic alterations were observed in all paired primary and metachronous carcinomas. The number of genetic mutations was higher in metachronous lesions than in primary lesions. <i>CDKN2A</i> and <i>SMAD4</i> were the most frequently mutated genes in all metachronous lesions. Common genetic mutations between primary and metachronous lesions were confirmed in all four cases, suggesting a common clonal origin.</p><p><strong>Conclusion: </strong>This study demonstrated that characteristic genetic alterations and their accumulation play important roles in metachronous BTC. This suggests that the increasing burden of gene mutations may play a crucial role in the carcinogenesis of metachronous BTC. Further investigation is required to validate these findings and elucidate the underlying molecular mechanisms.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"346-353"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490814","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}