Pub Date : 2025-10-09DOI: 10.1016/j.cancergen.2025.10.002
Jun Jiang, Xiaoshuai Chen, Xinjie Dong, Yanfang Wang, Jixuan Liu, Ting Liu, Xiaolei Bian, Ming Li, Yafang Liu
Objectives
RING finger proteins are a large family of proteins within the human genome that play essential roles in the regulation of physiological processes and have been implicated in cancer progression. However, the relationships among RING Finger Protein 121 (RNF121), E3 ubiquitin ligase, and tumorigenesis have yet to be determined. In this study, we aimed to comprehensively elucidate the functions of RNF121 in non-small cell lung cancer (NSCLC).
Methods
On the basis of MTT, colony formation, and Transwell assays, we evaluated RNF121-specific functions that were found to be closely associated with clinicopathological features.
Results
RNF121 expression was demonstrated to be closely associated with different diseases. By altering the levels of this protein in the A549 and H1299 cell lines, we discovered that this protein promotes cell proliferation, migration, and invasion.
Conclusion
This study is the first to demonstrate that RNF121 plays a prominent role in driving NSCLC progression and that its expression is correlated with clinicopathological features. Accordingly, this gene would serve not only as a key prognostic indicator but also as a novel potential therapeutic target for the treatment of NSCLC.
目的：无名指蛋白是人类基因组中的一个大家族蛋白，在生理过程的调节中发挥重要作用，并与癌症进展有关。然而，RING Finger Protein 121 （RNF121）、E3泛素连接酶与肿瘤发生之间的关系尚不明确。在本研究中，我们旨在全面阐明RNF121在非小细胞肺癌（NSCLC）中的功能。方法：基于MTT、菌落形成和Transwell试验，我们评估了与临床病理特征密切相关的rnf121特异性功能。结果：RNF121的表达与不同疾病密切相关。通过改变A549和H1299细胞系中这种蛋白的水平，我们发现这种蛋白促进细胞增殖、迁移和侵袭。结论：本研究首次证实RNF121在推动NSCLC进展中发挥突出作用，其表达与临床病理特征相关。因此，该基因不仅可以作为关键的预后指标，而且可以作为治疗非小细胞肺癌的新的潜在治疗靶点。
{"title":"RNF121 promotes the proliferation, migration, and invasion of lung cancer cell lines","authors":"Jun Jiang, Xiaoshuai Chen, Xinjie Dong, Yanfang Wang, Jixuan Liu, Ting Liu, Xiaolei Bian, Ming Li, Yafang Liu","doi":"10.1016/j.cancergen.2025.10.002","DOIUrl":"10.1016/j.cancergen.2025.10.002","url":null,"abstract":"<div><h3>Objectives</h3><div>RING finger proteins are a large family of proteins within the human genome that play essential roles in the regulation of physiological processes and have been implicated in cancer progression. However, the relationships among RING Finger Protein 121 (RNF121), E3 ubiquitin ligase, and tumorigenesis have yet to be determined. In this study, we aimed to comprehensively elucidate the functions of <em>RNF121</em> in non-small cell lung cancer (NSCLC).</div></div><div><h3>Methods</h3><div>On the basis of MTT, colony formation, and Transwell assays, we evaluated <em>RNF121</em>-specific functions that were found to be closely associated with clinicopathological features.</div></div><div><h3>Results</h3><div><em>RNF121</em> expression was demonstrated to be closely associated with different diseases. By altering the levels of this protein in the A549 and H1299 cell lines, we discovered that this protein promotes cell proliferation, migration, and invasion.</div></div><div><h3>Conclusion</h3><div>This study is the first to demonstrate that <em>RNF121</em> plays a prominent role in driving NSCLC progression and that its expression is correlated with clinicopathological features. Accordingly, this gene would serve not only as a key prognostic indicator but also as a novel potential therapeutic target for the treatment of NSCLC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 193-197"},"PeriodicalIF":2.1,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-02DOI: 10.1016/j.cancergen.2025.10.001
Ana Valeria Silva Alencar, Giulianna Aparecida Vieira Barreto, Maria Cláudia dos Santos Luciano, Clarissa Picanço Albuquerque, Rosane Oliveira de Sant’Ana, Paulo Goberlânio de Barros Silva, Flávio da Silveira Bittencourt, Valeska Portela Lima, Maria Júlia Barbosa Bezerra
To analyze the influence of Lynch Syndrome on the incidence of adverse reactions to antineoplastic treatment in patients with colorectal cancer. Observational and retrospective study based on analyzing electronic medical records of patients treated at Hospital Haroldo Juaçaba/Ceará Cancer Institute (HHJ/ICC). Patients with NCCN clinical criteria for Lynch Syndrome and a diagnosis of colorectal cancer were included, comparing the profile of adverse reactions to chemotherapy between those with and without pathogenic mutations associated with the syndrome. The sample consisted of 161 patients with suspected Lynch Syndrome, all undergoing chemotherapy. A higher frequency of adverse reactions was observed among patients without a pathogenic mutation for Lynch Syndrome. Approximately two-thirds of the sample reported adverse reactions, with nausea being the most common adverse event, followed by neurotoxicity and diarrhea. Patients with colorectal cancer without a pathogenic mutation for Lynch syndrome had a higher incidence of adverse reactions to chemotherapy. This finding may be related to biological and physiological factors, including greater cellular variability, the need for more intensive therapeutic regimens, and the influence of individual genetic variability. These results highlight the importance of personalized approaches in managing the side effects of cancer treatment.
分析Lynch综合征对结直肠癌患者抗肿瘤治疗不良反应发生率的影响。基于Haroldo juaaba医院/ ceearcancer Institute （HHJ/ICC）治疗患者电子病历分析的观察性和回顾性研究纳入符合Lynch综合征NCCN临床标准并诊断为结直肠癌的患者，比较具有和不具有与该综合征相关的致病性突变的患者化疗不良反应的概况。样本包括161名疑似Lynch综合征的患者，他们都在接受化疗。在没有Lynch综合征致病突变的患者中观察到更高频率的不良反应。大约三分之二的样本报告了不良反应，恶心是最常见的不良反应，其次是神经毒性和腹泻。无Lynch综合征致病突变的结直肠癌患者化疗不良反应发生率较高。这一发现可能与生物和生理因素有关，包括更大的细胞变异性，需要更强化的治疗方案，以及个体遗传变异性的影响。这些结果强调了个性化方法在管理癌症治疗副作用方面的重要性。
{"title":"Influence of lynch syndrome on the incidence of side effects to antineoplastic treatment of patients with colorectal cancer","authors":"Ana Valeria Silva Alencar, Giulianna Aparecida Vieira Barreto, Maria Cláudia dos Santos Luciano, Clarissa Picanço Albuquerque, Rosane Oliveira de Sant’Ana, Paulo Goberlânio de Barros Silva, Flávio da Silveira Bittencourt, Valeska Portela Lima, Maria Júlia Barbosa Bezerra","doi":"10.1016/j.cancergen.2025.10.001","DOIUrl":"10.1016/j.cancergen.2025.10.001","url":null,"abstract":"<div><div>To analyze the influence of Lynch Syndrome on the incidence of adverse reactions to antineoplastic treatment in patients with colorectal cancer. Observational and retrospective study based on analyzing electronic medical records of patients treated at Hospital Haroldo Juaçaba/Ceará Cancer Institute (HHJ/ICC). Patients with NCCN clinical criteria for Lynch Syndrome and a diagnosis of colorectal cancer were included, comparing the profile of adverse reactions to chemotherapy between those with and without pathogenic mutations associated with the syndrome. The sample consisted of 161 patients with suspected Lynch Syndrome, all undergoing chemotherapy. A higher frequency of adverse reactions was observed among patients without a pathogenic mutation for Lynch Syndrome. Approximately two-thirds of the sample reported adverse reactions, with nausea being the most common adverse event, followed by neurotoxicity and diarrhea. Patients with colorectal cancer without a pathogenic mutation for Lynch syndrome had a higher incidence of adverse reactions to chemotherapy. This finding may be related to biological and physiological factors, including greater cellular variability, the need for more intensive therapeutic regimens, and the influence of individual genetic variability. These results highlight the importance of personalized approaches in managing the side effects of cancer treatment.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 169-179"},"PeriodicalIF":2.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
High-grade serous ovarian carcinoma (HGSOC) accounts for 70% of all ovarian cancer cases and 80% of related deaths. TP53 mutations are common; however, other driving genetic factors are not well understood. In this study, we used RNA sequencing to explore the genetic background of HGSOC in patients with unclear profiles.
Methods
This study included 80 patients with a pathological diagnosis of HGSOC. RNA sequencing was performed to analyze gene expression and detect fusion.
Results
We identified 18 novel potential driver fusion gene candidates, including in-frame and frameshift fusions, in 80 patients with high-grade serous ovarian cancer (HGSOC). Of these, ST7-OT4::MET, STK24::DOCK9, GAB::PAK1, HDAC1::LCK, ESR1::LATS1, ZNF157::CDK16, NEK7::RP11–85M11.2, CAMKK1::R2RX1, HNRNPUL1::AXL, DYRK1A::GART, MAPKAPK2::DYRK3, and FER::GS1421I3.2 involved fusion partners harboring protein kinase domains. Notably, TAOK1::PIPOX and PSMD11::NLK were identified in the same case, similar to SH3PXD2A::BMPR1A and EIF3H::CAMK2D in another case. In addition, SLMAP::NTRK3 involves NTRK3, a known fusion partner. The remaining fusions, SWAP70::ZNF143, WDR25::YY1, and NR2F6::MYO9B, included partners with DNA-binding domains.
Conclusions
This study identified candidate driver fusion genes and suggested new therapeutic targets for HGSOCs.
{"title":"Identification of novel gene fusions in high-grade serous ovarian carcinoma: implications for tumorigenesis and targeted therapy","authors":"Katsuhiro Masago , Eiichi Sasaki , Yasuko Fujita , Shiro Fujita , Yoshitsugu Horio , Hiroaki Kuroda , Aiko Ogasawara , Kenji Tatsuno , Hiroyuki Aburatani , Katsutoshi Oda , Kosei Hasegawa , Hirokazu Matsushita","doi":"10.1016/j.cancergen.2025.09.012","DOIUrl":"10.1016/j.cancergen.2025.09.012","url":null,"abstract":"<div><h3>Background</h3><div>High-grade serous ovarian carcinoma (HGSOC) accounts for 70% of all ovarian cancer cases and 80% of related deaths. <em>TP53</em> mutations are common; however, other driving genetic factors are not well understood. In this study, we used RNA sequencing to explore the genetic background of HGSOC in patients with unclear profiles.</div></div><div><h3>Methods</h3><div>This study included 80 patients with a pathological diagnosis of HGSOC. RNA sequencing was performed to analyze gene expression and detect fusion.</div></div><div><h3>Results</h3><div>We identified 18 novel potential driver fusion gene candidates, including in-frame and frameshift fusions, in 80 patients with high-grade serous ovarian cancer (HGSOC). Of these, <em>ST7-OT4::MET, STK24::DOCK9, GAB::PAK1, HDAC1::LCK, ESR1::LATS1, ZNF157::CDK16, NEK7::RP11–85M11.2, CAMKK1::R2RX1, HNRNPUL1::AXL, DYRK1A::GART, MAPKAPK2::DYRK3,</em> and <em>FER::GS1421I3.2</em> involved fusion partners harboring protein kinase domains. Notably, <em>TAOK1::PIPOX</em> and <em>PSMD11::NLK</em> were identified in the same case, similar to <em>SH3PXD2A::BMPR1A</em> and <em>EIF3H::CAMK2D</em> in another case. In addition, <em>SLMAP::NTRK3</em> involves <em>NTRK3</em>, a known fusion partner. The remaining fusions, <em>SWAP70::ZNF143, WDR25::YY1</em>, and <em>NR2F6::MYO9B</em>, included partners with DNA-binding domains.</div></div><div><h3>Conclusions</h3><div>This study identified candidate driver fusion genes and suggested new therapeutic targets for HGSOCs.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 159-168"},"PeriodicalIF":2.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145266621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-26DOI: 10.1016/j.cancergen.2025.09.011
Yuan Wang , Xin Wan , Yutian Zhang , Jia Qi , Chao Li , Xiaonan Cui
Objective
To explore the role of ESRRA in esophageal squamous cell carcinoma (ESCC) progression and evaluate the antitumor effects of hydroxygenkwanin (HGK), focusing on its interaction with ESRRA and the underlying molecular mechanisms.
Methods
Cell viability, apoptosis, invasion, and proliferation were assessed in EC109 and TE-1 cells treated with HGK using CCK-8, Hoechst staining, Transwell, and colony formation assays. ESRRA expression was analyzed via qPCR and Western blot. An ESCC mouse model was established, with treatment groups receiving HGK. Serum IL-10 and IL-12 levels were measured by ELISA; tumor growth and toxicity were evaluated by histology. EMT marker expression was analyzed by IHC and RT-qPCR. TCGA database analysis explored ESRRA-related pathways and its link to the tumor microenvironment and patient survival.
Results
HGK inhibited EC109 and TE-1 cell proliferation and migration, especially in EC109 cells, by downregulating ESRRA in a dose-dependent manner. In vivo, HGK reduced tumor growth with minimal toxicity, though high doses showed possible renal effects. IL-12 levels decreased, and EMT markers were altered. ESRRA was overexpressed in ESCC tissues and correlated with EMT-related genes. TCGA analysis confirmed ESRRA’s association with poor survival in ESCC patients.
Conclusion
HGK effectively suppresses ESCC with low toxicity, primarily by inhibiting ESRRA and blocking EMT, highlighting its therapeutic potential.
{"title":"Study on the anticancer mechanism of hydroxygenkwanin in esophageal cancer via the ESRRA signaling pathway","authors":"Yuan Wang , Xin Wan , Yutian Zhang , Jia Qi , Chao Li , Xiaonan Cui","doi":"10.1016/j.cancergen.2025.09.011","DOIUrl":"10.1016/j.cancergen.2025.09.011","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the role of ESRRA in esophageal squamous cell carcinoma (ESCC) progression and evaluate the antitumor effects of hydroxygenkwanin (HGK), focusing on its interaction with ESRRA and the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>Cell viability, apoptosis, invasion, and proliferation were assessed in EC109 and TE-1 cells treated with HGK using CCK-8, Hoechst staining, Transwell, and colony formation assays. ESRRA expression was analyzed via qPCR and Western blot. An ESCC mouse model was established, with treatment groups receiving HGK. Serum IL-10 and IL-12 levels were measured by ELISA; tumor growth and toxicity were evaluated by histology. EMT marker expression was analyzed by IHC and RT-qPCR. TCGA database analysis explored ESRRA-related pathways and its link to the tumor microenvironment and patient survival.</div></div><div><h3>Results</h3><div>HGK inhibited EC109 and TE-1 cell proliferation and migration, especially in EC109 cells, by downregulating ESRRA in a dose-dependent manner. In vivo, HGK reduced tumor growth with minimal toxicity, though high doses showed possible renal effects. IL-12 levels decreased, and EMT markers were altered. ESRRA was overexpressed in ESCC tissues and correlated with EMT-related genes. TCGA analysis confirmed ESRRA’s association with poor survival in ESCC patients.</div></div><div><h3>Conclusion</h3><div>HGK effectively suppresses ESCC with low toxicity, primarily by inhibiting ESRRA and blocking EMT, highlighting its therapeutic potential.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 180-192"},"PeriodicalIF":2.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The transcription factor ZHX2 exerts paradoxical roles in cancer, acting as either an oncogene or tumor suppressor in a context-dependent manner. This duality stems from ZHX2’s regulation of key processes including cell cycle, apoptosis, EMT, stemness, and metabolism. Consequently, ZHX2 may impacts tumor cell growth, migration, and immune evasion, positioning it as a promising therapeutic target. This short communication synthesizes current understanding of ZHX2’s molecular structure, transcriptional regulation, and its critical modulation of oncogenic and tumor-suppressive pathways across various cancers. We highlight its potential utility as a prognostic biomarker and its implications for precision medicine, chemotherapy, targeted therapy, and immunotherapy. However, translating ZHX2-targeting strategies faces significant hurdles, particularly concerning tissue-specific restoration and integration with existing treatments. Future research should prioritize overcoming these barriers and exploring ZHX2’s epigenetic regulatory potential.
{"title":"Molecular mechanisms underlying the oncogenic and tumor-suppressive roles of ZHX2 in cancers","authors":"Yifan Wei , Haiyang Guo , Jingjie Zhou , Da Shi, Liqiang Hao","doi":"10.1016/j.cancergen.2025.09.010","DOIUrl":"10.1016/j.cancergen.2025.09.010","url":null,"abstract":"<div><div>The transcription factor ZHX2 exerts paradoxical roles in cancer, acting as either an oncogene or tumor suppressor in a context-dependent manner. This duality stems from ZHX2’s regulation of key processes including cell cycle, apoptosis, EMT, stemness, and metabolism. Consequently, ZHX2 may impacts tumor cell growth, migration, and immune evasion, positioning it as a promising therapeutic target. This short communication synthesizes current understanding of ZHX2’s molecular structure, transcriptional regulation, and its critical modulation of oncogenic and tumor-suppressive pathways across various cancers. We highlight its potential utility as a prognostic biomarker and its implications for precision medicine, chemotherapy, targeted therapy, and immunotherapy. However, translating ZHX2-targeting strategies faces significant hurdles, particularly concerning tissue-specific restoration and integration with existing treatments. Future research should prioritize overcoming these barriers and exploring ZHX2’s epigenetic regulatory potential.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 128-132"},"PeriodicalIF":2.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-18DOI: 10.1016/j.cancergen.2025.09.008
Wanfang Yang , Jing Xu , Shuhua Cao , Ning Wang , Zhuanghui Hao , Qing Wang , Yanhong Tan , Xiuhua Chen , Zhifang Xu , Yaofang Zhang , Jianmei Chang , Xiaojuan Wang , Fanggang Ren , Hongwei Wang
Mutations in Isocitrate Dehydrogenase-1 (IDH1) and IDH2 lead to abnormal histone hypermethylation and DNA modifications, disrupting cell differentiation, yet the clinical and prognostic significance of these mutations in primary acute myeloid leukemia (AML) remains debated. This study retrospectively analyzed 181 newly diagnosed AML patients, categorizing them into IDH1mut, IDH2mut, and IDHwt groups to compare clinical features, mutational profiles, and outcomes. IDH1 and IDH2 mutations were detected in 7.7 % (14/181) and 11.6 % (21/181) of cases, respectively. Patients with IDH mutations were older, had higher platelet counts, elevated WT1 mRNA expression, and lower white blood cell counts compared to IDHwt patients. Notably, IDH1mut patients showed no significant OS difference (P = .153), whereas IDH2mut patients exhibited significantly shorter overall survival (OS) than IDHwt patients (HR = 1.844, 95 % CI: 1.008–3.792, P = .047). Additionally, IDH1mut patients with DNMT3A co-mutations also demonstrated shorter DFS and OS (P = .013 and P = .003, respectively), while IDH2mut patients with co-mutations in NPM1, ASXL1, or SRSF2 had reduced disease-free survival (DFS) and OS (P < .05).
These findings suggest that early detection of IDH1/2 mutations and associated clinical features at AML diagnosis could provide a rationale for targeted therapy with IDH inhibitors, potentially improving patient outcomes.
{"title":"Differential impact of IDH1/2 mutations on outcome in adult acute myeloid leukemia patients","authors":"Wanfang Yang , Jing Xu , Shuhua Cao , Ning Wang , Zhuanghui Hao , Qing Wang , Yanhong Tan , Xiuhua Chen , Zhifang Xu , Yaofang Zhang , Jianmei Chang , Xiaojuan Wang , Fanggang Ren , Hongwei Wang","doi":"10.1016/j.cancergen.2025.09.008","DOIUrl":"10.1016/j.cancergen.2025.09.008","url":null,"abstract":"<div><div>Mutations in Isocitrate Dehydrogenase-1 (IDH1) and IDH2 lead to abnormal histone hypermethylation and DNA modifications, disrupting cell differentiation, yet the clinical and prognostic significance of these mutations in primary acute myeloid leukemia (AML) remains debated. This study retrospectively analyzed 181 newly diagnosed AML patients, categorizing them into IDH1mut, IDH2mut, and IDHwt groups to compare clinical features, mutational profiles, and outcomes. IDH1 and IDH2 mutations were detected in 7.7 % (14/181) and 11.6 % (21/181) of cases, respectively. Patients with IDH mutations were older, had higher platelet counts, elevated WT1 mRNA expression, and lower white blood cell counts compared to IDHwt patients. Notably, IDH1mut patients showed no significant OS difference (<em>P</em> = .153), whereas IDH2mut patients exhibited significantly shorter overall survival (OS) than IDHwt patients (HR = 1.844, 95 % CI: 1.008–3.792, <em>P</em> = .047). Additionally, IDH1mut patients with DNMT3A co-mutations also demonstrated shorter DFS and OS (<em>P</em> = .013 and <em>P</em> = .003, respectively), while IDH2mut patients with co-mutations in NPM1, ASXL1, or SRSF2 had reduced disease-free survival (DFS) and OS (<em>P</em> < .05).</div><div>These findings suggest that early detection of IDH1/2 mutations and associated clinical features at AML diagnosis could provide a rationale for targeted therapy with IDH inhibitors, potentially improving patient outcomes.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 133-140"},"PeriodicalIF":2.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-18DOI: 10.1016/j.cancergen.2025.09.009
Aarthi Goverdhan , Lisa Mullineaux , Amber Pryzbylski , Claire Teigen , Kevin C. Halling , Sheryl K. Elkin , Beth A. Pitel
Accurate clinical interpretation of somatic cancer variants is critical for diagnosis and guidance of precision oncology treatment. As the depth and breadth of genomic sequencing increased, laboratories developed independent standards for the classification of somatic variants. In response, a set of standards for classification were published by a collaboration among Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC) and Variant Interpretation for Cancer Consortium (VICC). This study evaluated these standards and compared the resulting classifications to the classifications generated by a clinical decision support software system, QIAGEN Clinical Insight (QCI) Interpret One, a system using a version of the 2015 consensus guidelines by the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) customized for somatic assessment. The published variant set for validation was utilized and expanded by conducting a retrospective analysis using real-world cancer variants drawn from oncology cases tested at Mayo Clinic. For “oncogenic” and “likely oncogenic” variants in the combined datasets, automated classifications by the QCI system were 97.2% concordant with those assessed using the ClinGen/CGC/VICC system. The ClinGen/CGC/VICC standards led to more conservative variant classifications, with a larger proportion of variants assigned to the “variant of unknown significance” and “likely benign” designations. This study demonstrates that the ClinGen/CGC/VICC guidelines and clinical decision support tools can be effectively used together to facilitate somatic variant classification and interpretation.
{"title":"Comparison of somatic variant oncogenicity classification using ClinGen/CGC/VICC guidelines and QIAGEN Clinical Insight Interpret decision support software","authors":"Aarthi Goverdhan , Lisa Mullineaux , Amber Pryzbylski , Claire Teigen , Kevin C. Halling , Sheryl K. Elkin , Beth A. Pitel","doi":"10.1016/j.cancergen.2025.09.009","DOIUrl":"10.1016/j.cancergen.2025.09.009","url":null,"abstract":"<div><div>Accurate clinical interpretation of somatic cancer variants is critical for diagnosis and guidance of precision oncology treatment. As the depth and breadth of genomic sequencing increased, laboratories developed independent standards for the classification of somatic variants. In response, a set of standards for classification were published by a collaboration among Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC) and Variant Interpretation for Cancer Consortium (VICC). This study evaluated these standards and compared the resulting classifications to the classifications generated by a clinical decision support software system, QIAGEN Clinical Insight (QCI) Interpret One, a system using a version of the 2015 consensus guidelines by the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) customized for somatic assessment. The published variant set for validation was utilized and expanded by conducting a retrospective analysis using real-world cancer variants drawn from oncology cases tested at Mayo Clinic. For “oncogenic” and “likely oncogenic” variants in the combined datasets, automated classifications by the QCI system were 97.2% concordant with those assessed using the ClinGen/CGC/VICC system. The ClinGen/CGC/VICC standards led to more conservative variant classifications, with a larger proportion of variants assigned to the “variant of unknown significance” and “likely benign” designations. This study demonstrates that the ClinGen/CGC/VICC guidelines and clinical decision support tools can be effectively used together to facilitate somatic variant classification and interpretation.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 151-158"},"PeriodicalIF":2.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-16DOI: 10.1016/j.cancergen.2025.09.007
Xiaojuan Zhang , Juan Xie , Tao Fu , Zhen Gao , Hengrui Liu , Zhenshan Yang
Laminin, a critical component of the basement membrane, plays an indispensable role in numerous biological processes. Among its subunits, laminin γ2 (LAMC2) emerges as a key player in the progression of cancer. This review delves into the current understanding of LAMC2′s role, highlighting its significant contribution to cancer development through promoting cell proliferation, invasion, and vasculogenic mimicry, as well as inhibiting apoptosis. Notably, LAMC2 expression is markedly increased in cancerous tissues compared to normal counterparts, with higher levels of LAMC2 correlating with poorer survival rates. This correlation underscores LAMC2′s potential as a diagnostic and prognostic marker across various cancers. Furthermore, the increasing importance of LAMC2 as a viable target for cancer therapy is explored. This review aims to provide a thorough overview of LAMC2′s involvement in cancer progression, prognostic implications, potential therapeutic target, and involved signaling pathway, and to outline future research directions in this promising field.
{"title":"The multidimensional role of laminin γ2 (LAMC2) on cancer progression","authors":"Xiaojuan Zhang , Juan Xie , Tao Fu , Zhen Gao , Hengrui Liu , Zhenshan Yang","doi":"10.1016/j.cancergen.2025.09.007","DOIUrl":"10.1016/j.cancergen.2025.09.007","url":null,"abstract":"<div><div>Laminin, a critical component of the basement membrane, plays an indispensable role in numerous biological processes. Among its subunits, laminin γ2 (LAMC2) emerges as a key player in the progression of cancer. This review delves into the current understanding of LAMC2′s role, highlighting its significant contribution to cancer development through promoting cell proliferation, invasion, and vasculogenic mimicry, as well as inhibiting apoptosis. Notably, LAMC2 expression is markedly increased in cancerous tissues compared to normal counterparts, with higher levels of LAMC2 correlating with poorer survival rates. This correlation underscores LAMC2′s potential as a diagnostic and prognostic marker across various cancers. Furthermore, the increasing importance of LAMC2 as a viable target for cancer therapy is explored. This review aims to provide a thorough overview of LAMC2′s involvement in cancer progression, prognostic implications, potential therapeutic target, and involved signaling pathway, and to outline future research directions in this promising field.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 122-127"},"PeriodicalIF":2.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-10DOI: 10.1016/j.cancergen.2025.09.006
Jun Zhang , Yang Xu , Xiao Han , Yan Gao , Zhanbo Wei , Xu Sun
Galectin-9 plays multiple roles in various tumors and exerts immune regulation within the tumor microenvironment. It is closely associated with tumor prognosis. This study aimed to analyze the expression of galectin-9 in the colon tumor microenvironment. The results indicated that galectin-9 expression is higher in the colon tumor microenvironment compared to adjacent normal tissues. Furthermore, high expression of galectin-9 was related to M2-type macrophages, which promote tumor development by increasing tumor cell viability, migration, and invasion. Notably, high expression of galectin-9 in colon tumor microenvironment contributed to the polarization of M2 cells, marked by high expression of arginase-1, CD163, and IL-10 and low expression of iNOS. When M0 macrophages were treated with galectin-9 and co-cultured with colon cancer cell lines, it resulted in increased cancer cell growth, migration, and invasion by promoting the differentiation of THP-1 monocytes into the M2 macrophages. The specific mechanism by which galectin-9 promotes M2 polarization involves its binding to Tim-3, recruiting PI3K-p85 to the cytoplasmic domain of Tim-3. This interaction further affects the PI3K/Akt signal pathway, leading to M2 polarization.
{"title":"Galectin-9 promotes colon cancer development by polarizing macrophages toward the M2 phenotype","authors":"Jun Zhang , Yang Xu , Xiao Han , Yan Gao , Zhanbo Wei , Xu Sun","doi":"10.1016/j.cancergen.2025.09.006","DOIUrl":"10.1016/j.cancergen.2025.09.006","url":null,"abstract":"<div><div>Galectin-9 plays multiple roles in various tumors and exerts immune regulation within the tumor microenvironment. It is closely associated with tumor prognosis. This study aimed to analyze the expression of galectin-9 in the colon tumor microenvironment. The results indicated that galectin-9 expression is higher in the colon tumor microenvironment compared to adjacent normal tissues. Furthermore, high expression of galectin-9 was related to M2-type macrophages, which promote tumor development by increasing tumor cell viability, migration, and invasion. Notably, high expression of galectin-9 in colon tumor microenvironment contributed to the polarization of M2 cells, marked by high expression of arginase-1, CD163, and IL-10 and low expression of iNOS. When M0 macrophages were treated with galectin-9 and co-cultured with colon cancer cell lines, it resulted in increased cancer cell growth, migration, and invasion by promoting the differentiation of THP-1 monocytes into the M2 macrophages. The specific mechanism by which galectin-9 promotes M2 polarization involves its binding to Tim-3, recruiting PI3K-p85 to the cytoplasmic domain of Tim-3. This interaction further affects the PI3K/Akt signal pathway, leading to M2 polarization.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 141-150"},"PeriodicalIF":2.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-05DOI: 10.1016/j.cancergen.2025.09.005
Junxu Chen , Dongwook Kim , Jae Young Kim , Hyung Jun Kim
Background
Oral squamous cell carcinoma (OSCC) carries substantial mortality despite surgery-based management. Reliable biomarkers and practical prognostic tools are needed to guide individualized care.
Methods
Transcriptomic and clinical data from TCGA and multiple GEO cohorts were integrated. Candidate genes identified by differential expression analysis, WGCNA, and PPI were refined using LASSO and Random Forest, then entered a multivariable Cox model to derive a three-gene risk score. Performance was assessed with Kaplan–Meier curves, time-dependent ROC, and calibration, and validated across internal, external, and combined datasets. Expression was examined by RT-qPCR and Western blot in OSCC and normal oral cell lines. Immune infiltration and pathway enrichment analyses were conducted to contextualize biology.
Results
The three-gene signature (CXCL12, PLAU, PXDN) separated risk groups in the training cohort with 1/3/5-year AUCs of 0.767/0.625/0.714. In three independent external cohorts, high-risk patients consistently had worse overall survival (log-rank p = 0.0092, ≤0.0001, ≤0.0001), with time-AUC ranges of 0.581–0.747 (1-year), 0.555–0.795 (3-year), and 0.603–0.812 (5-year). In TCGA, the score remained prognostic across sex, age, smoking, drinking, and stage III/IV subgroups (all p ≤ 0.05), with a consistent trend in stage I/II (p = 0.09). A nomogram integrating clinical variables with the risk score achieved a C-index of 0.63 with good 1–5-year calibration and outperformed TNM staging alone (C-index 0.63 vs 0.58; 95 % CI 0.58–0.70 vs 0.54–0.61). RT-qPCR/Western blot confirmed consistent differential expression of all three biomarkers. Immune-infiltration and pathway analyses revealed distinct microenvironmental and molecular features across risk strata.
Conclusion
We present a robust, externally validated three-gene prognostic model for OSCC, supported by experimental evidence and superior to TNM staging for discrimination, offering a practical nomogram for individualized risk estimation from 1 to 5 years.
背景：尽管手术治疗，口腔鳞状细胞癌（OSCC）的死亡率仍然很高。需要可靠的生物标志物和实用的预后工具来指导个体化护理。方法整合来自TCGA和多个GEO队列的转录组学和临床数据。通过差异表达分析、WGCNA和PPI鉴定的候选基因使用LASSO和Random Forest进行细化，然后进入多变量Cox模型，得出三基因风险评分。通过Kaplan-Meier曲线、随时间变化的ROC曲线和校准进行评估，并通过内部、外部和联合数据集进行验证。用RT-qPCR和Western blot检测OSCC和正常口腔细胞株的表达。免疫浸润和途径富集分析进行了背景生物学。结果三基因标记（CXCL12， PLAU， PXDN）分离了训练队列的风险组，1/3/5年auc为0.767/0.625/0.714。在三个独立的外部队列中，高危患者的总生存率均较差（log-rank p = 0.0092,≤0.0001,≤0.0001），时间auc范围为0.581-0.747（1年），0.555-0.795（3年）和0.603-0.812（5年）。在TCGA中，评分在性别、年龄、吸烟、饮酒和III/IV期亚组中仍具有预测作用（均p≤0.05），在I/II期中趋势一致（p = 0.09）。综合临床变量和风险评分的nomogram C-index为0.63，具有良好的1 - 5年校准效果，优于单纯的TNM分期（C-index 0.63 vs 0.58; 95% CI 0.58 - 0.70 vs 0.54-0.61）。RT-qPCR/Western blot证实了这三种生物标志物的一致差异表达。免疫浸润和途径分析揭示了不同风险层的微环境和分子特征。结论我们提出了一个可靠的、外部验证的OSCC三基因预后模型，该模型有实验证据支持，在区分方面优于TNM分期，为1 - 5年的个体化风险估计提供了一个实用的nomogram。
{"title":"Development and multi-cohort validation of a prognostic risk score model for oral squamous cell carcinoma based on a three-gene signature","authors":"Junxu Chen , Dongwook Kim , Jae Young Kim , Hyung Jun Kim","doi":"10.1016/j.cancergen.2025.09.005","DOIUrl":"10.1016/j.cancergen.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Oral squamous cell carcinoma (OSCC) carries substantial mortality despite surgery-based management. Reliable biomarkers and practical prognostic tools are needed to guide individualized care.</div></div><div><h3>Methods</h3><div>Transcriptomic and clinical data from TCGA and multiple GEO cohorts were integrated. Candidate genes identified by differential expression analysis, WGCNA, and PPI were refined using LASSO and Random Forest, then entered a multivariable Cox model to derive a three-gene risk score. Performance was assessed with Kaplan–Meier curves, time-dependent ROC, and calibration, and validated across internal, external, and combined datasets. Expression was examined by RT-qPCR and Western blot in OSCC and normal oral cell lines. Immune infiltration and pathway enrichment analyses were conducted to contextualize biology.</div></div><div><h3>Results</h3><div>The three-gene signature (<em>CXCL12, PLAU, PXDN</em>) separated risk groups in the training cohort with 1/3/5-year AUCs of 0.767/0.625/0.714. In three independent external cohorts, high-risk patients consistently had worse overall survival (log-rank <em>p</em> = 0.0092, ≤0.0001, ≤0.0001), with time-AUC ranges of 0.581–0.747 (1-year), 0.555–0.795 (3-year), and 0.603–0.812 (5-year). In TCGA, the score remained prognostic across sex, age, smoking, drinking, and stage III/IV subgroups (all <em>p</em> ≤ 0.05), with a consistent trend in stage I/II (<em>p</em> = 0.09). A nomogram integrating clinical variables with the risk score achieved a C-index of 0.63 with good 1–5-year calibration and outperformed TNM staging alone (C-index 0.63 vs 0.58; 95 % CI 0.58–0.70 vs 0.54–0.61). RT-qPCR/Western blot confirmed consistent differential expression of all three biomarkers. Immune-infiltration and pathway analyses revealed distinct microenvironmental and molecular features across risk strata.</div></div><div><h3>Conclusion</h3><div>We present a robust, externally validated three-gene prognostic model for OSCC, supported by experimental evidence and superior to TNM staging for discrimination, offering a practical nomogram for individualized risk estimation from 1 to 5 years.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 88-98"},"PeriodicalIF":2.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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