Translational cancer research最新文献

{"title":"Value of <i>ZSCAN9</i> in the treatment and survival prediction of hepatocellular carcinoma: a bioinformatics study.","authors":"Suwei Jing, Wenlei Dong, Chao Zhan","doi":"10.21037/tcr-2025-1597","DOIUrl":"10.21037/tcr-2025-1597","url":null,"abstract":"<p><strong>Background: </strong>Zinc finger and SCAN domain containing 9 (<i>ZSCAN9</i>), also known as <i>zinc finger factor 193</i> (<i>ZNF193</i>), has been associated with the enhanced expression of X-chromosomal genes in certain organs. However, its role in hepatocellular carcinoma (HCC) remains unclear. This study examines the mechanism of <i>ZSCAN9</i> in HCC and analyze its expression, prognostic value, clinical relevance, immune correlation, signaling pathways, and drug sensitivity, thus providing new insights into its potential as a therapeutic target for HCC.</p><p><strong>Methods: </strong>The Tumor Immune Estimation Resource (TIMER) 2.0 database was used to analyze the pancancer expression of <i>ZSCAN9</i>, its differential expression between tumor and normal tissues, and the associations with overall survival (OS) and recurrence-free survival (RFS). Additionally, The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases, along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were used to analyze the pathways, immune levels, and drug sensitivity related to <i>ZSCAN9</i>'s involvement in HCC.</p><p><strong>Results: </strong><i>ZSCAN9</i> was differentially expressed in HCC, with its high expression being associated with poor prognosis (P<0.05). <i>ZSCAN9</i> was also correlated with several biological functions, such as DNA replication, G2M checkpoint, tumor proliferation, DNA repair (R>0.3; P<0.05), and fatty acid degradation (R<-0.3; P<0.05). The results of immune correlation analysis showed that <i>ZSCAN9</i> was positively correlated with the abundance of T helper cells (R>0.2; P<0.05) and negatively correlated with that of dendritic cells (DCs), cytotoxic cells, neutrophils, plasmacytoid DCs, B cells, and interdigitating DCs (R<-0.2; P<0.05). <i>ZSCAN9</i> was positively correlated with CD274 level (R=0.29), and the results of drug sensitivity analysis indicated that patients with high <i>ZSCAN9</i> were more responsive to several drugs, including sorafenib, 5-fluorouracil, etoposide, and AKT inhibitor VIII, as compared to those with low expression.</p><p><strong>Conclusions: </strong><i>ZSCAN9</i> may be a biological target capable of predicting recurrence and survival time in patients with HCC and may be involved in the regulation of angiogenesis; moreover, its expression may influence the drug sensitivity of sorafenib, 5-fluorouracil, etoposide, and AKT inhibitor VIII.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"5077-5092"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of hub genes related to radiosensitivity and prognosis in rectal cancer.","authors":"Hui Yang, Yin Liu, Mengdi Hao, Huimin Li, Dajin Yuan, Lei Ding","doi":"10.21037/tcr-2025-521","DOIUrl":"10.21037/tcr-2025-521","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is one of the main treatment methods for rectal cancer (RC). However, radioresistance often leads to treatment failure and poor prognosis. This study aimed to explore the core molecules associated with radiosensitivity and prognosis of RC.</p><p><strong>Methods: </strong>GSE133057 containing RC radiosensitivity information was downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between the complete response (CR) group and the incomplete response (iCR) group were identified. Immune genes were obtained from the ImmPort database. Radiosensitivity-related immune genes (RRIGs) were obtained by intersecting DEGs and the immune genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to study the biological functions of RRIGs. Transcriptomic and clinical data of RC were downloaded from The Cancer Genome Atlas (TCGA) database, and the entire cohort was randomly divided into training and testing sets at a ratio of 7:3. Prognostic genes were selected by univariate and multivariate Cox analyses, and a risk model and nomogram were built subsequently. External dataset validation was performed. The relationship between the risk model and immune cell infiltration was analyzed by single-sample gene set enrichment analysis (ssGSEA).</p><p><strong>Results: </strong>A total of 76 RRIGs were identified, and they were mainly involved in cytokine-cytokine receptor interaction, TNF signaling pathway, cAMP signaling pathway, Toll-like receptor (TLR) signaling pathway, and so on. <i>BMP2</i>, <i>COLEC10</i>, <i>MASP2</i>, and <i>GCGR</i> were screened as prognostic genes after Cox regression analysis. The risk score model demonstrated good performance in predicting prognosis as proved by the receiver operating characteristic (ROC) curves. Multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for RC. Moreover, we found that the immune microenvironment was different between the high and low risk groups, and these four genes were associated with different immune cell infiltration.</p><p><strong>Conclusions: </strong>We identified four key genes: <i>BMP2</i>, <i>COLEC10</i>, <i>MASP2</i>, and <i>GCGR</i>, which play significant roles in the radiosensitivity, immune microenvironment, and prognosis of RC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4759-4773"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065529","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":"METTL11A serves as a novel therapeutic target for acute myeloid leukemia through regulation of the p38-MAPK pathway.","authors":"Ju Li, Jiasi Zhang, Pei Zhang","doi":"10.21037/tcr-2025-602","DOIUrl":"10.21037/tcr-2025-602","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) represents a heterogeneous blood malignancy and is the most common and severe acute leukemia in adult. The METTL gene family is increasingly being recognized as involved in cancer progression. The aim of the study is to elaborate on the specific role of METTL11A in AML.</p><p><strong>Methods: </strong>In this research, cell viability, transwell assay, and scratch wound assay were utilized to assess cell proliferation and migration in AML cells. Western blot was used to determine the expression of proteins and the activation of signal pathway. Virtual screening was performed to obtain potential inhibitors of METTL11A.</p><p><strong>Results: </strong>Our findings indicated that METTL11A expression levels were strongly associated with AML patients' prognosis. Overexpressed METTL11A by constructing stable cell lines promoted proliferation and migration in AML cells. Conversely, knockdown of METTL11A inhibited cell viability and migration. Through gene sets enrichment analysis, we validated the inactivated p38-mitogen-activated protein kinase (MAPK) pathway under silenced METTL11A expression. In high throughput molecular docking, S-Adenosyl-L-methionine disulfate tosylate was predicted to bind METTL11A, which was validated to inhibit cell proliferation and migration.</p><p><strong>Conclusions: </strong>The results suggested that METTL11A is a novel biomarker and therapeutic target in AML, which is mediated by suppressed MAPK pathway.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4561-4573"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065586","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 functional role of exosomal <i>miRNA-675-3p</i> derived from patients with hepatocellular carcinoma.","authors":"Chi Liang, Xiang Ji, Shan Liu, Liancheng Xu, Yicheng Xiong, Guanyi Cao","doi":"10.21037/tcr-2025-1372","DOIUrl":"10.21037/tcr-2025-1372","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) is one of the most common solid tumors, resulting in poor survival and high mortality worldwide. MicroRNAs (miRNAs) contained in serum exosomes are being increasing used as targets for disease diagnosis and treatment. However, the role and the diagnostic potential of exosome-transported miRNAs in HCC remain largely underexplored. Therefore, this study aims to identify differentially expressed exosomal miRNAs in the serum of HCC patients and healthy individuals, clarify the biological function of the key miRNAs in HCC progression, and explore its potential as a diagnostic and therapeutic biomarker for HCC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, the serum-derived exosomes of patients with HCC and healthy individuals were characterized via transmission electron microscopy (TEM), Western blot assay, and nanoparticle tracking analysis (NTA). The serum-derived exosomes were labeled with PKH-67, and the transport to recipient HCC cells was observed with confocal microscopy. Differentially expressed miRNAs (DEmiRs) encapsulated in serum-derived exosomes were screened via miRNA sequencing, the expression of which was verified through quantitative real-time polymerase chain reaction (qRT-PCR). The association between &lt;i&gt;miR-675-3p&lt;/i&gt; and clinicopathological features was investigated via the chi-squared test. The gain and loss of function of &lt;i&gt;miR-675-3p&lt;/i&gt; in HCC cells were examined through transfection with mimics and inhibitor. Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, and Transwell assays were conducted to test the biological effects of overexpressed and inhibited &lt;i&gt;miR-675-3p&lt;/i&gt; on HCC cells &lt;i&gt;in vitro&lt;/i&gt;. Tumor xenograft models and immunohistochemistry (IHC) were performed to assess the malignant progression of HCC cells with downregulated &lt;i&gt;miR-675-3p&lt;/i&gt; &lt;i&gt;in vivo&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Uptake of exosomes from patients with HCC promoted the malignant phenotype of recipient cells. &lt;i&gt;miRNA-675-3p&lt;/i&gt; within exosomes was confirmed to be upregulated in the serum of patients with HCC as compared with that of healthy donors. The chi-squared test results showed that &lt;i&gt;miRNA-675-3p&lt;/i&gt; was associated with poor survival. Overexpression of &lt;i&gt;miRNA-675-3p&lt;/i&gt; promoted the proliferation, invasion, and colony formation of HCC cells &lt;i&gt;in vitro&lt;/i&gt;, while downregulation of &lt;i&gt;miRNA-675-3p&lt;/i&gt; had the opposite biological effects on HCC cells and inhibited tumor growth and malignant progression &lt;i&gt;in vivo&lt;/i&gt;. Furthermore&lt;i&gt;,&lt;/i&gt; bioinformatics analysis indicated that &lt;i&gt;miRNA-675-3p&lt;/i&gt; was involved in certain cellular processes, especially in lipid metabolism and regulation of several signaling pathways such as &lt;i&gt;PI3K/AKT&lt;/i&gt; pathways and &lt;i&gt;PPAR&lt;/i&gt; pathways.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;&lt;i&gt;miRNA-675-3p&lt;/i&gt; was upregulated in the serum of patients with HCC and exerted an oncogenic role in HCC cells via the targeti","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"5012-5027"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065724","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":"Development and validation of a preoperative nomogram for predicting residual tumor risk in breast cancer patients undergoing excisional biopsy.","authors":"Yangfan Fan, Yiwei Wu, Fangfang Chen, Fang Wan, Dianlei Liu, Jingpei Long, Tao Zhang","doi":"10.21037/tcr-2025-850","DOIUrl":"10.21037/tcr-2025-850","url":null,"abstract":"<p><strong>Background: </strong>Current research on breast-conserving surgery (BCS) focuses on recurrence and survival but overlooks the issue of residual tumors post-excisional biopsy. These remnants, crucial for surgical planning, often necessitate additional excisions, impacting BCS success. Our 5-year study of excisional biopsy patients identifies risk factors for residual tumors, offering insights to improve surgical decisions.</p><p><strong>Methods: </strong>This study examined 233 breast cancer patients split into training and validation groups (2:1 ratio). Logistic regression models identified predictors of post-biopsy residual tumors status, leading to the creation and validation of a preoperative nomogram for residual risk.</p><p><strong>Results: </strong>In this study of 233 patients, 23.9% with BCS had residual tumors after biopsy, significantly less than those in the non-BCS group (P<0.001). Tumor size, biopsy method, and histopathological subtype were crucial in predicting residual tumors and were used to develop a nomogram, which showed strong predictive accuracy for preoperative residual tumor status. This tool enhances preoperative risk stratification and aids in the formulation of personalized surgical strategies by providing visual quantification of the probabilities associated with oncological clearance parameters.</p><p><strong>Conclusions: </strong>We developed a clinically practical nomogram for predicting residual tumor status following excisional biopsy, facilitating preoperative risk stratification and personalized surgical strategy. Further prospective studies are necessary to evaluate its generalizability and accuracy.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4965-4975"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064779","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":"Elevated suicide risk in thyroid cancer patients: determining mortality rates and identifying predictive factors using Surveillance, Epidemiology, and End Results (SEER) data.","authors":"Jiaojiao Ma, Xi Wang, Shanshan Wang, Xuejiao Yu, Yang Li, Zhe Sun, Huilin Li, Yong Cheng, Bo Zhang","doi":"10.21037/tcr-2025-1617","DOIUrl":"10.21037/tcr-2025-1617","url":null,"abstract":"<p><strong>Background: </strong>Despite thyroid cancer's favorable prognosis, population-level data on suicide risk and predictive factors remain limited, necessitating targeted mental health interventions. Patients experience significant psychological distress due to diagnostic/treatment uncertainties, particularly in the active surveillance era. This study quantified suicide mortality and identified risk predictors among US thyroid cancer patients.</p><p><strong>Methods: </strong>We analyzed 328,264 histologically confirmed thyroid cancer patients [International Classification of Diseases for Oncology (ICD-O) C73.9] from the Surveillance, Epidemiology and End Results (SEER) database (2000-2021). Exclusions: non-suicide deaths, cases without microscopic confirmation, and incomplete records. We calculated standardized mortality ratios (SMRs) versus the general population and analyzed demographic (age, sex, race, income) and clinical predictors (stage, treatment history, tumor sequence) using Cox regression. A nomogram was developed from significant predictors and internally validated.</p><p><strong>Results: </strong>Among 328,264 patients (75.3% female; median age 48 years), 282 died by suicide, yielding an SMR of 1.24 [95% confidence interval (CI): 0.72-1.99]. Key high-risk subgroups included males [hazard ratio (HR) =1.93], patients aged 10-39 years, and those diagnosed between 2016-2020 (HR =6.17). The nomogram demonstrated good predictive accuracy, with a C-index of 0.795.</p><p><strong>Conclusions: </strong>Thyroid cancer patients show elevated suicide risk, particularly young males and recent diagnoses. While the nomogram may help identify high-risk subgroups, its clinical utility requires external validation and integration with psychosocial assessments.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"5127-5141"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065396","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":"Enhanced antitumor efficacy of sorafenib and everolimus combination in pancreatic neuroendocrine neoplasms through mTOR inhibition.","authors":"Hongxia Zheng, Yue Gao, Mujie Ye, Jianan Bai, Min Liu, Qin Long, Jinhao Chen, Xinyun Qiang, Qiyun Tang","doi":"10.21037/tcr-2024-2424","DOIUrl":"10.21037/tcr-2024-2424","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic neuroendocrine neoplasms (pNENs) represent a rare group of highly heterogeneous tumors derived from pancreatic epithelial cells exhibiting neuroendocrine differentiation properties. Everolimus, an oral inhibitor of mTOR, is the most promising drug for patients with unresectable, metastatic disease, particularly in progressive well-differentiated pNENs. Sorafenib is utilized in the treatment of hepatocellular carcinoma (HCC), renal cell carcinoma, and differentiated thyroid cancer. Furthermore, it plays an indispensable role in the management of multisystem malignancies. This study aims to investigate the effects and mechanisms of sorafenib, as well as its potential for combination use with everolimus in pNENs.</p><p><strong>Methods: </strong>QGP-1and BON-1cells were collected from routine <i>in vitro</i> culture and treated with various concentrations of sorafenib, everolimus, and dual-drug combinations for 24 hours. The capacity of these medications to influence tumor activity was evaluated through the use of the Cell Counting Kit-8 (CCK-8) assay, cloning assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, and analysis of the xenograft tumor model. Western blot analysis was conducted to detect the level of mTOR in QGP-1 and BON-1 cells.</p><p><strong>Results: </strong>Compared to the control group, the proliferation and migration of sorafenib-treated cells were significantly inhibited. Furthermore, as drug concentration increased, the proliferation rates of both cell types decreased. Notably, the inhibition of cell proliferation was more pronounced in the sorafenib and everolimus combination group than in the single-drug group. Western blot results indicated that the expression level of mTOR was down-regulated in the experimental group after treatment with sorafenib, everolimus, and the dual-drug combination for 24 hours, compared to the control group. In experiments involving animals, tumors in the groups treated with both high and low doses of sorafenib were smaller than those observed in the control group, and liver metastasis was suppressed in the experimental groups when compared to the control.</p><p><strong>Conclusions: </strong>Sorafenib can inhibit the proliferation and migration of pNENs by down-regulating the mTOR pathway. The combination of sorafenib and everolimus exhibits a stronger anti-tumor effect.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4586-4597"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065465","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 SLC25A10 promotes cellular senescence and impedes hepatocellular carcinoma progression.","authors":"Yi-Hong Ding, Tian-Yi Huang, Shi-Meng Xu, Min Li, Xiang Shi, Wen-Yan Sun, Cui-Hua Lu, Zhao-Xiu Liu, Wei Huang","doi":"10.21037/tcr-2024-2319","DOIUrl":"10.21037/tcr-2024-2319","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality with limited therapeutic options. Solute carrier family 25 member 10 (SLC25A10), a mitochondrial transporter linked to metabolic regulation and tumor progression, has unclear roles in HCC pathogenesis. This study aimed to elucidate the functional and mechanistic contributions of SLC25A10 to HCC development.</p><p><strong>Methods: </strong>The International Cancer Genome Consortium (ICGC) database, GAO <i>et al.</i> dataset, quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB), and immunohistochemistry (IHC) staining were used to explore the expression levels of SLC25A10 in HCC tissues and cell lines. Functional assays [cell counting kit-8, colony formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, SA-β-galactosidase staining, and flow cytometry] and a subcutaneous xenograft mouse model were employed to assess the effects of SLC25A10 knockdown on proliferation, senescence, and tumorigenesis. Finally, NecroX-7, a high mobility group box 1 (HMGB1) inhibitor, was used to delineate the underlying molecular mechanisms involved in cell senescence caused by SLC25A10 knockdown.</p><p><strong>Results: </strong>The protein and messenger RNA (mRNA) levels of SLC25A10 in HCC tissues were higher than those in adjacent normal tissues. Knockdown of SLC25A10 suppressed cell proliferation, induced senescence-associated β-galactosidase activity, and triggered G1 phase arrest by downregulating cyclin-dependent kinase 4 (<i>CDK4</i>)/<i>Cyclin D1</i> and upregulating cyclin-dependent kinase inhibitor 2A (<i>CDKN2A</i>). <i>In vivo</i>, SLC25A10 silencing reduced tumor growth and decreased KI67/proliferating cell nuclear antigen (PCNA) expression, while enhancing HMGB1, a senescence-associated secretory phenotype (SASP) marker. Mechanically, pharmacological inhibition of HMGB1 with NecroX-7 partially reversed the anti-proliferative and pro-senescent effects of SLC25A10 knockdown, restoring cell cycle progression.</p><p><strong>Conclusions: </strong>SLC25A10 promotes HCC progression by suppressing cellular senescence. Pharmacological or genetic inhibition of SLC25A10 triggers tumor suppression through HMGB1-mediated SASP signaling, positioning SLC25A10 as a promising therapeutic target for HCC intervention.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4939-4954"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of mechanosensitive ion channel-related molecular subtypes and key genes for ovarian cancer.","authors":"Lu Zhang, Li Wang, Min Wang, Kefei Peng, Huihui Chen, Xin Wang, Ling Zhou","doi":"10.21037/tcr-2025-1219","DOIUrl":"10.21037/tcr-2025-1219","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a significant health concern due to the complex nature of its causes, difficulties in early detection, and low 5-year survival rate. The function of mechanosensitive ion channel (MIC)-related prognostic gene signatures in OC is still not clearly defined. Our aim was to clarify the function of the MIC in OC.</p><p><strong>Methods: </strong>We created OC subtypes and a prognostic model based on MICs to forecast patient outcomes using RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA) database.</p><p><strong>Results: </strong>In this study, the top 20 genes were identified based on their relevance scores and included <i>PIEZO1, SCN5A, KCNQ1, CFTR, PIEZO2, KCNMA1, ASIC2, CACNA1C, ASIC3, SCN1A, TRPV4, TRPV1, KCNN4, SCNN1B, SCNN1A, CACNA1B, SCNN1G, TRPM7, KCNK2</i>, and <i>TRPA1</i>. Patients were distinctly categorized into a high-risk group (cluster 1) and a low-risk group (cluster 2) based on genes related to MICs. Functional analysis revealed that the upregulated differentially expressed genes (DEGs) in cluster 1 were significantly enriched in pathways such as focal adhesion, axon guidance, proteoglycans in cancer, extracellular matrix (ECM)-receptor interaction, Wnt signaling pathway, Hippo signaling pathway, and thyroid hormone signaling pathway. Conversely, the downregulated DEGs in cluster 1 were predominantly enriched in pathways including oxidative phosphorylation, chemical carcinogenesis-reactive oxygen species, and nonalcoholic fatty liver disease. Gene Ontology (GO) analysis of the upregulated DEGs in cluster 1 indicated significant enrichment in biological pathways related to ECM organization, cell-substrate adhesion, and cell junction assembly. Conversely, the downregulated DEGs in cluster 1 were significantly enriched in pathways associated with oxidative phosphorylation, adenosine triphosphate metabolic processes, and cellular respiration. The estimation of immune scores revealed differences between the high- and low-risk groups. Using least absolute shrinkage and selection operator and Cox regression analyses, we identified a set of 20 genes linked to MICs in OC, from which three key genes-<i>PIEZO1</i>, <i>CACNA1C</i>, and <i>TRPV4</i>-were further selected. Single-cell RNA sequencing demonstrated that <i>CACNA1C</i> was expressed in fibroblasts and myofibroblasts, <i>PIEZO1</i> was expressed across all five cell subtypes, and <i>TRPV4</i> was expressed in fibroblasts and monocytes or macrophages.</p><p><strong>Conclusions: </strong>This study initially identified unique molecular subtypes and key genes for patients with OC from the novel angle of MICs.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"5166-5175"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the transcription factor <i>SOX8</i> in hepatocellular carcinoma development and lymph node metastasis.","authors":"Xiong Teng, Tian-Man Li, Kai Peng, Yu-Hua Li, Han-Jing Zhang, Bin Ge, Hai-Xiang Xie, Ke-Jian Yang, Chong-Jiu Qin, Xi-Wen Liao, Guang-Zhi Zhu, Xin Zhou, Tao Peng","doi":"10.21037/tcr-2025-94","DOIUrl":"10.21037/tcr-2025-94","url":null,"abstract":"<p><strong>Background: </strong>Lymph node metastasis (LNM) is one of the forms of hepatocellular carcinoma (HCC) dissemination, a phenomenon that is strongly correlated with an adverse prognosis. The transcription factor <i>SOX8</i> has been implicated in tumor progression in other malignancies, but its prognostic significance and mechanistic role in HCC LNM remain unexplored. This study aims to explore the prognostic significance and mechanistic role of the transcription factor <i>SOX8</i> in HCC LNM.</p><p><strong>Methods: </strong>We retrospectively enrolled 387 HCC patients who underwent radical hepatectomy with lymph-node dissection between 2013 and 2021, among whom 57 were LNM-positive and the remaining 330 were negative. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier curves and compared by log-rank test; independent prognostic factors were identified with Cox proportional-hazards regression. <i>SOX8</i> mRNA levels in matched primary tumors and metastatic lymph nodes were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Functional impacts of <i>SOX8</i> knockdown and overexpression were assessed in HCC cell lines via proliferation, migration, and invasion assays. Changes in epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, Vimentin) were examined by Western blot.</p><p><strong>Results: </strong>LNM, microvascular invasion (MVI), and the China Liver Cancer (CNLC) stage emerged as independent predictors of both shorter RFS and OS in the matched cohort; metastatic lymph nodes exhibited a 3.8-fold increase in <i>SOX8</i> mRNA compared to primary tumors (P<0.001). <i>In vitro</i>, <i>SOX8</i> knockdown significantly inhibited HCC cell proliferation, migration, and invasion, whereas <i>SOX8</i> overexpression produced the opposite effects. At the molecular level, <i>SOX8</i> modulation altered EMT marker expression-specifically, <i>SOX8</i> overexpression reduced E-cadherin while upregulating N-cadherin and Vimentin-demonstrating that <i>SOX8</i> drives EMT to promote HCC cell invasiveness and metastatic potential.</p><p><strong>Conclusions: </strong>In summation, this study established a correlation between LNM and diminished RFS and OS among HCC patients. Moreover, it demonstrated the significant role of <i>SOX8</i> in HCC progression and LNM, which appears to modulate the malignant phenotype of HCC cells, encompassing enhanced proliferation, stem cell-like properties, and invasive migration through the induction of EMT. These collective findings implicate <i>SOX8</i> as a promising candidate for targeted therapeutic intervention in HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4882-4905"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065616","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}