Translational cancer research最新文献

{"title":"Limitations and oncological uncertainties of intraductal laser ablation for pathological nipple discharge.","authors":"Mariam Rizk, Kefah Mokbel","doi":"10.21037/tcr-2025-426","DOIUrl":"10.21037/tcr-2025-426","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"3892-3893"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822675","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":"Stemness-hypoxia genes <i>PPARGC1A</i>, <i>PFKFB3</i>, and <i>SLC2A5</i> are associated with prognosis and tumor immune microenvironment in hepatocellular carcinoma.","authors":"Dan Wang, Ruotian Wang, Yuewen Zhang, Zhitao Li, Hong Zheng, Wanggang Xu","doi":"10.21037/tcr-24-2030","DOIUrl":"10.21037/tcr-24-2030","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The stemness of cancer cells and hypoxic microenvironment in HCC influence tumor progression and resistance to anti-tumor therapies. Herein, we aimed to combine tumoral stemness and hypoxia features to evaluate the prognosis and tumor immune microenvironment (TIME) in HCC.</p><p><strong>Methods: </strong>Based on the HCC data from The Cancer Genome Atlas (TCGA) database, the mRNA expression-based stemness index (mRNAsi) was calculated, followed by acquisition of stemness-hypoxia genes. The prognostic stemness-hypoxia genes were identified using Cox regression analysis and a stemness-hypoxia prognostic model was constructed. The prognostic capacity of the model was validated, and the associations between the model and immune characteristics were evaluated. Moreover, the differential expression of model genes in HCC cells under hypoxia condition was determined.</p><p><strong>Results: </strong>A three-gene prognostic signature based on the stemness-hypoxia genes (<i>PPARGC1A</i>, <i>PFKFB3</i>, and <i>SLC2A5</i>) was constructed. The Kaplan-Meier curve validated the prognostic capacity of the model. <i>PPARGC1A</i> and <i>PFKFB3</i> were independent prognostic factors for HCC: <i>PPARGC1A</i> expression was significantly associated with favorable overall survival (OS) of HCC patients, while <i>PFKFB3</i> expression was related to poor OS. Furthermore, the high-risk group was associated with advanced stages, infiltrated tumor-promoting immune cells, and elevated expression of immune checkpoints. The risk score also exhibited prognostic capacity for the OS and predictive value for the immune microenvironment in HCC. Finally, <i>SLC2A5</i> was significantly up-regulated in HepG2 cells compared to LO-2 cells. Additionally, elevated <i>SLC2A5</i> expression and reduced <i>PPARGC1A</i> and <i>PFKFB3</i> expression were observed in both Hep3B and HepG2 cells under hypoxia condition.</p><p><strong>Conclusions: </strong>Our established stemness-hypoxia gene signature showed favorable prognosis performance for HCC and was related to TIME. Our findings provide novel insights into the prognostic evaluation of HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4009-4023"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822682","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":"Impact of smoking on the effectiveness of different non-small-cell lung cancer therapies.","authors":"Kairui Yang","doi":"10.21037/tcr-2025-145","DOIUrl":"10.21037/tcr-2025-145","url":null,"abstract":"<p><strong>Background and objective: </strong>Smoking reshapes tumor genetics, host immunity, and drug metabolism in non-small-cell lung cancer (NSCLC), yet its therapy-specific impact is often overlooked. This review sought to clarify how current, former, and never smokers respond to each major NSCLC modality and to outline opportunities for treatment optimization.</p><p><strong>Methods: </strong>A systematic search of PubMed, Web of Science, and Google Scholar up to April 2025 identified 146 high-quality trials, cohorts, and meta-analyses that reported outcomes by smoking status. Hazard ratios, response rates, and complication data, and random-effects meta-analyses were performed.</p><p><strong>Key content and findings: </strong>Immune-checkpoint inhibitors improved overall survival across all smoking groups (pooled HR_OS =0.74), although active smokers exhibited shorter response durability because of faster drug clearance and persistent immune dysfunction despite higher tumor-mutational burden and programmed death-ligand 1 (PD-L1) expression. Never-smokers achieved markedly better progression-free survival with EGFR tyrosine-kinase inhibitors [hazard ratio (HR) 0.32 <i>vs.</i> 0.54 in smokers], whereas ALK inhibitors showed little disparity. Smoking attenuated chemotherapy and radiotherapy benefits through cytochrome-P450 induction, tumor hypoxia, and enhanced DNA repair, and it increased postoperative pulmonary-complication rates two- to five-fold after lung resection; cessation ≥8 weeks reduced but did not eliminate this surgical risk.</p><p><strong>Conclusions: </strong>Smoking status is a potent, modifiable determinant of NSCLC outcomes. Embedding structured cessation programs, tailoring dose or schedule, and incorporating smoking-informed molecular profiling into routine care could heighten efficacy and reduce toxicity. Future trials should stratify participants by detailed tobacco history to advance truly personalized, behavior-integrated oncology.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4461-4473"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822697","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":"Erratum: Long non-coding RNA <i>SNHG17</i> promotes gastric cancer progression by inhibiting <i>P15</i> and <i>P16</i>.","authors":"","doi":"10.21037/tcr-2025b-13","DOIUrl":"10.21037/tcr-2025b-13","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.21037/tcr-2023-01.].</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4474-4475"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822707","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":"Unlocking the future of immunotherapy with circulating tumor DNA (ctDNA)-based liquid biopsy in non-small cell lung cancer.","authors":"Bartłomiej Tomasik, Bartosz Kamil Sobocki","doi":"10.21037/tcr-2025-326","DOIUrl":"10.21037/tcr-2025-326","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"3894-3898"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822715","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":"TSPAN9 inhibits malignant progression of hepatocellular carcinoma.","authors":"Li Xu, Buyun Yan, Zhaonv Yao, Yansong Hu, Yuhua Chen, Di Li, Cheng Lin, Shengkui Tan, Xiaonian Zhu","doi":"10.21037/tcr-2025-174","DOIUrl":"10.21037/tcr-2025-174","url":null,"abstract":"<p><strong>Background: </strong>Tetraspanins (TSPANs) are a critical family for cell migration, which have been implicated in a variety of activities including cancer. Previous study showed that tetraspanin 9 (TSPAN9) plays an important role in gastric cancer. In this study, we aim to explore the biological functions of TSPAN9 in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyze TSPAN9 expression, prognostic mutations, somatic copy number alterations (sCNAs), and tumor immune characteristics in 33 tumors. Immunohistochemistry images of TSPAN9 in HCC tissues were obtained from the Human Protein Atlas (HPA) database. Survival curves were generated using the Kaplan-Meier Plotter database. The proliferation, migration, and invasion abilities of HCC cells were assessed using Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays.</p><p><strong>Results: </strong>TSPAN9 was deregulated in various tumor types, and its expression was lower in HCC tissues than that of normal liver tissues (P<0.05). Moreover, TSPAN9 expression had a correlation with the prognosis of tumor patients, and HCC patients with low TSPAN9 expression showed a poor prognosis (Log-rank P<0.05). In addition, we detected that TSPAN9 was significantly decreased in HCC cells (P<0.01). As compared to the control cells, overexpression of TSPAN9 in HCC cells significantly reduced cell proliferation, slowed the wound healing rate, and inhibited the invasive and migration ability (all P<0.05). TCGA database analysis revealed a relationship between the expression of TSPAN9 and epithelium-mesenchymal transformation (EMT) factors.</p><p><strong>Conclusions: </strong>Downregulated expression of TSPAN9 indicates a poor prognosis of HCC patients. TSPAN9 can inhibit the proliferation and metastasis of HCC cells.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4046-4057"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822714","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":"Erratum: CK1α-targeting inhibits primary and metastatic colorectal cancer <i>in vitro</i>, <i>ex vivo</i>, in cell-line-derived and patient-derived tumor xenograft mice models.","authors":"","doi":"10.21037/tcr-2025b-9","DOIUrl":"10.21037/tcr-2025b-9","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.21037/tcr.2020.02.13.].</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3880-3881"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675751","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":"Erratum: Impact of apatinib in combination with osimertinib on EGFR T790M-positive lung adenocarcinoma.","authors":"","doi":"10.21037/tcr-2025b-10","DOIUrl":"10.21037/tcr-2025b-10","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.21037/tcr.2019.09.35.].</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3877-3879"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675752","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 single-cell and bulk RNA sequencing reveals prognostic and immunotherapy-associated myofibroblastic cancer-associated fibroblast subtypes in head and neck squamous cell carcinoma.","authors":"Xiufang Qiu, Yuhao Lin, Qian Li, Ameya A Asarkar, Zhiheng Ke, Yiying Xu, Lisha Chen","doi":"10.21037/tcr-2025-649","DOIUrl":"10.21037/tcr-2025-649","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblasts (CAFs) are involved in some critical aspects of the pathogenesis of head and neck squamous cell carcinoma (HNSCC), including the formation of a tumor-permissive extracellular matrix (ECM) structure, angiogenesis, and the immune and metabolic reprogramming of the tumor microenvironment (TME). This study aimed to examine the plasticity and metabolic heterogeneity of CAFs in HNSCC patients before and after immunotherapy.</p><p><strong>Methods: </strong>An integrated single-cell and bulk RNA sequencing (RNA-seq) analysis based on data from the GSE195832, GSE65868, and The Cancer Genome Atlas (TCGA)-HNSCC datasets was conducted. The functional plasticity and transcriptome diversity of the categorized CAF subtypes were analyzed using the DoRothEA tool and scMetabolism package. The relationship between the genes specifically expressed in the myofibroblast-like cancer-associated fibroblast (myCAF) subtype and prognosis was then examined by univariate and multivariate analyses. The influence of myCAF on immune cell modulation within the TME was analyzed using the Seurat and clusterProfiler packages. The therapeutic strategies for HNSCC were explored using the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing datasets.</p><p><strong>Results: </strong>In total, seven types of cells were annotated based on 11 clusters. The CAFs were then re-categorized into the following three subtypes: inflammatory cancer-associated fibroblasts (iCAFs), proliferating cancer-associated fibroblasts (pCAFs), and myCAFs. The percentage of myCAFs was reduced in HNSCC following the immunotherapy. The functional plasticity of the CAFs was further confirmed by the diverse enriched pathways. Notably, the myCAFs were closely associated with DNA repair, oxidative phosphorylation, and transcription factor E2F targets. Further, the myCAFs were found to be the subtype most relevant to the prognosis of HNSCC and were found to be involved in modulating the immune cells in the TME of HNSCC. Additionally, a higher myCAF score was related to the higher half-maximal inhibitory concentration (IC50) values of D-4476, GW-583340, spautin-1, and VER-155008, and the lower IC50 values of JTE-607, TG100-115, ML320, and TGX-221. Moreover, patients with lower myCAF scores responded better to immunotherapy.</p><p><strong>Conclusions: </strong>This study, which was based on single-cell and bulk RNA-seq analyses, showed the plasticity and metabolic heterogeneity of CAFs in HNSCC. Our findings may contribute to understandings of the immunotherapy response in HNSCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3730-3745"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675760","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":"Investigation of effects of CFI-400945 and ionizing radiation on DNA damage response in triple-negative breast cancer.","authors":"Harjot Athwal, Vasudeva Bhat, Alison L Allan, Armen Parsyan","doi":"10.21037/tcr-2024-2495","DOIUrl":"10.21037/tcr-2024-2495","url":null,"abstract":"<p><p>Breast cancer is the leading cause of cancer-related morbidity and mortality in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, often resistant to therapies including radiation treatment (RT). Developing new strategies for TNBC treatment is of paramount importance. In our previous studies, we have shown that a novel drug, Polo-like kinase 4 inhibitor CFI-400945, acts synergistically with RT to enhance antiproliferative effects in TNBC. Since one of the main anticancer mechanisms of RT is deoxyribonucleic acid (DNA) damage with ensuing DNA damage response (DDR) activation, in the current study, we aimed to investigate if and how CFI-400945 modulates DDR in response to RT. Using MDA-MB-231 and MDA-MB-468 TNBC cell lines, we investigated the levels and the foci formation of γ-H2AX, Ku70 and Rad51 proteins-the markers of DNA damage, non-homologous end joining (NHEJ) and homologous recombination (HR) repair pathways, respectively. We demonstrate that RT induces sustained DNA damage that is not further meaningfully enhanced or prolonged by CFI-400945. We also observed cell-line-dependent differences in the timing of activation of NHEJ and HR pathways in response to RT, and that CFI-400945 might lead to impeding RT-induced NHEJ pathway activation or result in earlier activation of the HR pathway. Notably, despite activation of the DDR responses, DNA damage persisted for 24 or more hours after RT. While some of these observations were cell-line dependent (emphasizing known molecular heterogeneity of TNBC), we highlight that canonical DDR pathways activity in response to RT might be inefficient and modulated by drugs, such as CFI-400945-a cancer cell vulnerability that warrants further investigations for better understanding the biology of TNBC, its responses to treatment and novel drug development.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3822-3832"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675761","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}