Translational cancer research最新文献

{"title":"Analysis of clinicopathological characteristics and prognosis of appendiceal neuroendocrine tumors: a retrospective cohort study based on the SEER database.","authors":"Xia Ren, Ganhong Wang, Jian Chen, Luojie Liu, Dan Li","doi":"10.21037/tcr-2025-239","DOIUrl":"10.21037/tcr-2025-239","url":null,"abstract":"<p><strong>Background: </strong>Appendiceal neuroendocrine tumors (ANETs) are rare, and there is a pressing clinical need for population-level data on their clinicopathological characteristics and prognosis to guide clinical decision-making. This study aimed to investigate the clinicopathological features and prognostic outcomes of patients with ANETs using the Surveillance, Epidemiology, and End Results (SEER) database.</p><p><strong>Methods: </strong>We included patients diagnosed with ANETs from 2000 to 2020. Participant inclusion was based on confirmed ANET diagnosis in the SEER database. Clinical factors, including tumor grade, stage, surgical status, and patient demographics, were assessed. Patients were followed up through the SEER database to record survival outcomes. The Kaplan-Meier method and Cox proportional hazards models were employed to evaluate overall survival (OS) and cancer-specific survival (CSS).</p><p><strong>Results: </strong>A total of 4,870 patients were enrolled, with females accounting for 61.3%. The median age was 40 years. Most patients presented with well-differentiated tumors (89.4%) and T1 stage disease (86.0%). Lymph node (4.6%) and distant (1.0%) metastases were rare. Surgical intervention was performed on 99.2% of patients. The 5-year OS and CSS rates were 92.8% and 97.2%. Multivariate Cox analysis revealed age [hazard ratio (HR) =10.05, P<0.001], female sex (compared to male, HR =0.70, P=0.004), and M stage (HR =2.35, P=0.01) as predictors of OS, while age (HR =10.12, P<0.001), poorly differentiated grade (HR =4.64, P=0.008), undifferentiated grade (HR =8.99, P=0.02), female sex (compared to male, HR =0.57, P=0.005), T4 stage (HR =3.24, P=0.01), and M stage (HR =5.44, P<0.001) were associated with CSS. After propensity score matching (PSM), males still exhibited significantly worse OS and CSS than females (P=0.003), and elderly patients had poorer OS and CSS compared to younger patients (P<0.001). However, among elderly patients, no significant differences in OS or CSS were observed between partial colectomy (PC) and subtotal colectomy (SC) groups (P=0.36 and P=0.07, respectively).</p><p><strong>Conclusions: </strong>ANETs patients generally present with early-stage disease and favorable prognosis. However, the males and the elders tend to have worse prognosis than their female and younger counterparts. These findings suggest that closer monitoring and potentially more aggressive treatment strategies may be warranted for these high-risk groups. For elderly patients, PC may be a more favorable surgical option, balancing efficacy and morbidity.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4804-4821"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065481","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 disulfidptosis-related long non-coding RNA signature to predict the prognosis, immunotherapy, and chemotherapy options in acute myeloid leukemia.","authors":"Minglei Huang, Longze Zhang, Ye Liu, Shuangmin Wang, Sikan Jin, Zhixu He, Xianyao Wang","doi":"10.21037/tcr-2025-441","DOIUrl":"10.21037/tcr-2025-441","url":null,"abstract":"<p><strong>Background: </strong>Disulfidptosis, a recently identified programmed cell death mechanism, has emerged as a critical regulator in tumorigenesis and demonstrates significant prognostic value across multiple cancer types. However, the prognostic significance of disulfidptosis-related long non-coding RNAs (DRLs) in acute myeloid leukemia (AML) and their functional implications in the tumor immune microenvironment (TIME) remain poorly characterized. Furthermore, the expression patterns and regulatory mechanisms of DRLs in AML require systematic investigation to elucidate their potential clinical applications. The study aims to investigate the prognostic and immunotherapeutic implications of DRLs in AML.</p><p><strong>Methods: </strong>RNA sequencing and clinical data for AML samples, as well as genotype-tissue expression (GTEx) normal bone marrow samples, were sourced from the University of California Santa Cruz (UCSC) database. Initially, DRLs were identified using Pearson correlation analysis. Subsequently, univariate Cox proportional hazards regression analysis was employed to identify long non-coding RNAs (lncRNAs) associated with prognosis. Key prognostic biomarkers were then selected through least absolute shrinkage and selection operator (LASSO) regression, stepwise Cox regression (StepCox), CoxBoost, and random survival forest (RSF) methods. A prognostic model was developed utilizing multivariate Cox regression analysis, and correlations between DRL risk scores, the AML immune microenvironment, and therapeutic agents were predicted. Furthermore, the expression levels of these DRLs in AML cell lines were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR).</p><p><strong>Results: </strong>We identified eight pivotal DRLs and developed a DRLs-based risk model (DRLs-RM). Patients classified in the low-risk cohort exhibited prolonged survival compared to those in the high-risk cohort. Multivariate Cox proportional hazards analysis demonstrated that DRL risk scores function as an independent prognostic biomarker for AML. Enrichment analysis revealed that DRL risk scores correlate with apoptotic pathways and NADPH oxidoreductase activity. Furthermore, DRL risk scores showed significant associations with the AML immune microenvironment, including elevated expression of various immune checkpoint molecules and human leukocyte antigen (HLA) genes in the high-risk group. Drug sensitivity profiling indicated that high-risk patients exhibit increased sensitivity to agents such as axitinib and cyclin-dependent kinase 9 (CDK9) inhibitors.</p><p><strong>Conclusions: </strong>The prognostic model incorporating eight DRLs demonstrates high accuracy and reliability in predicting survival outcomes for AML patients, thereby identifying potential therapeutic targets for future AML treatment strategies.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4491-4506"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors and treatment strategies for female reproductive system carcinosarcoma with metastasis.","authors":"Huijie Wu, Peiqiong Huo, Miao Dong, Ying Xiao, Lewei Tu","doi":"10.21037/tcr-2025-697","DOIUrl":"10.21037/tcr-2025-697","url":null,"abstract":"<p><strong>Background: </strong>Carcinosarcomas are rare, aggressive tumors of the female reproductive tract, with limited knowledge regarding their progression, metastasis, risk factors, and treatment, especially in advanced stages. This study aimed to investigate the risk factors and treatment outcomes for metastatic carcinosarcoma using a population-based approach.</p><p><strong>Methods: </strong>A retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database was conducted in order to identify patients diagnosed with carcinosarcoma and to analyze metastatic trends and patterns. Chi-square tests, Cox regression models, and the Kaplan-Meier method were used to identify risk factors and to assess the outcomes of various treatment strategies.</p><p><strong>Results: </strong>A total of 6,479 patients with carcinosarcoma were identified, with an estimated median cancer-specific survival (CSS) of 29 months. There were 775 patients in the metastatic cohort, with an estimated median CSS of 9 months. The metastasis patterns were mostly one-site metastasis (N=318, 41.03%), and the most common metastases were lung metastasis (N=153, 19.74%), followed by liver metastasis (N=96, 12.39%). A range of variables such as age, race, marital status, stage, grade, and size were found to be risk factors for metastatic carcinosarcoma in the univariable Cox model, but only tumor size was found to be an independent risk factor in the multivariable Cox model. Surgery and chemotherapy were associated with significant increases in survival, but radiotherapy was not.</p><p><strong>Conclusions: </strong>Carcinosarcoma is rare but aggressive and often results in lung and liver metastases. We conclude from our analysis that tumor size is an independent prognostic risk factor in patients with metastases, and we recommend both surgery and chemotherapy for these patients.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4748-4758"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065645","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 prognosis model for patients with brain-metastasis non-small cell lung cancer by machine-learning.","authors":"Jingxin Liu, Yibing Wang, Xianwei Zhou, Meijin Reng, Ziyue Xiang, Ruimin Chang, Wen Hao, Xitai Sun, Yang Yang","doi":"10.21037/tcr-2025-131","DOIUrl":"10.21037/tcr-2025-131","url":null,"abstract":"<p><strong>Background: </strong>Brain metastasis, the most prevalent site of lung cancer metastasis, implies a grim prognosis. Adopting the best treatment approach is crucial for improving the survival of these patients. Therefore, this study aimed to develop a personalized prognostic model for brain-metastasized non-small cell lung cancer (BM-NSCLC) patients to aid in clinical decision-making.</p><p><strong>Methods: </strong>The study enrolled BM-NSCLC patients who were single-primary and had not undergone radical surgery from 2010 to 2021. The Kaplan-Meier method analysis was utilized to assess overall survival (OS) and cancer-specific survival (CSS) under different treatments. Univariable and multivariable Cox regression analyses were conducted to ascertain independent prognostic factors. The dataset was partitioned into training (70%) and validation (30%) cohorts for the development and assessment of random forest (RF), logistic regression (LR), support vector machine (SVM), and K-nearest neighbor (KNN) models. The efficacy of the models was evaluated through the calculation of area under the curve (AUC) of the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). A user-friendly web app was developed via shinyapps.io to increase the accessibility for clinicians.</p><p><strong>Results: </strong>A total of 3,171 eligible samples were ultimately included in the study. Survival analysis indicated that patients who underwent metastasis site surgery combined with radiotherapy based on chemotherapy exhibited a more favorable prognosis compared to alternative treatment modalities within the scope of this study. The RF model demonstrated superior predictive accuracy for 1-year-OS, with an AUC of 0.89 in validation cohorts (n=951), and a more refined DCA profile.</p><p><strong>Conclusions: </strong>In the case of patients with BM-NSCLC, the integration of radiation therapy with surgery for metastasis site based on systematic treatment yielded the most significant benefits. The importance of a comprehensive treatment strategy that integrates chemotherapy, surgery, and radiotherapy for these patients was emphasized. Additionally, a clinical decision-support tool constructed from this dataset, demonstrated robust discrimination, excellent calibration, and notable clinical utility. This tool will effectively assist clinical practitioners in making more personalized clinical decisions for patients.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4638-4648"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065089","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":"Effects of different cancer-directed therapies on mortality of patients with stage I pulmonary large cell neuroendocrine carcinoma: a retrospective cohort study based on the SEER database.","authors":"Shijun Chen, Mohan Weng, Yanru Jiang, Tingting Li, Qicai Li, Chengling Zhao","doi":"10.21037/tcr-2024-2551","DOIUrl":"10.21037/tcr-2024-2551","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of lung tumors with the characteristics of both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), but has a worse prognosis. At present, there is no consensus on the optimal clinical therapy of LCNEC. This study aims to explore the effects of different cancer-directed therapies on mortality of stage I LCNEC patients.</p><p><strong>Methods: </strong>Data of this retrospective cohort study were extracted from the Surveillance Epidemiology and End Results (SEER) 2004-2015. Surgery, radiotherapy and their combination therapy were considered as cancer-directed therapy. The univariate and multivariate competing-risks model and COX proportional hazard model were utilized to explore the effect of different cancer-directed therapies on the all-cause mortality and cancer-species mortality of stage I LCNEC patients respectively and described as hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analysis was conducted to further evaluate the effect.</p><p><strong>Results: </strong>A total of 469 LCNEC patients were included, with 326 deaths recorded by December 31, 2015. Significant differences were observed between survivors and deceased patients in age, year of diagnosis, number of lymph nodes, type of surgery, use of radiation, combined treatments, and cancer-specific mortality. In the fully adjusted model, sublobectomy alone showed a lower HR compared to other treatments. No significant difference of mortality was found between patients who underwent lobectomy alone and sublobectomy alone. No statistically significant differences in mortality were found between patients receiving radiation combined with sublobectomy or lobectomy and those receiving sublobectomy alone. In patients younger than 65 years, combined radiation and other treatments increased mortality compared to sublobectomy alone. In patients older than 65 years, radiation or extended resection also increased mortality. Sublobectomy was the most favorable treatment for female patients and those classified as American Joint Committee on Cancer (AJCC) T1. Male patients who underwent lobectomy exhibited better prognoses. Extended resection or radiation alone or combined with other treatment in patients with cancer laterality increased mortality risk.</p><p><strong>Conclusions: </strong>Sublobectomy alone appears to be an effective treatment option for stage I LCNEC patients, outperforming combined therapies involving radiation and resection. Radiation therapy requires careful consideration, as it showed no significant mortality benefit when used alone or combined with sublobectomy or lobectomy. Lobectomy provided better prognoses for male patients, and radiation or extended resection offered limited advantages. And these findings need to be further confirmed by large-scale randomized controlled trails in the future.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4906-4919"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065249","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":"Exploration of signature-related FAM genes and correlation between FAM50A expression and the pathogenesis and prognosis of hepatocellular carcinoma.","authors":"Shaohan Wu, Sijun Chen, Xiaofang Sun, Xujian Chen","doi":"10.21037/tcr-2025-171","DOIUrl":"10.21037/tcr-2025-171","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) ranks among the deadliest malignancies worldwide, with limited therapeutic options and poor prognosis for advanced-stage patients. The family with sequence similarity (FAM) genes are expected to be potential regulators in tumorigenesis, but their roles in HCC remain poorly understood. This study aimed to systematically investigate the expression profiles and functional roles of FAM genes in HCC.</p><p><strong>Methods: </strong>We leveraged multiple databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC), to assess the expression patterns, prognostic implications, DNA methylation, genomic alterations, and associated tumor immune microenvironments of FAM genes. Differentially expressed genes were pinpointed using the DESeq2 package. Least absolute shrinkage and selection operator (LASSO) Cox regression and a nomogram model were employed to identify prognostic FAM genes and estimate the survival outcomes for HCC patients. We performed tissue microarrays and immunohistochemistry on samples from 48 HCC patients to evaluate <i>FAM50A</i> expression. <i>FAM50A</i> was also knocked down in HCC cell lines to investigate its biological functions.</p><p><strong>Results: </strong>Five overexpressed and signature-related FAM genes (<i>FAM50A</i>, <i>FAM83D</i>, <i>FAM104B</i>, <i>FAM220A</i>, and <i>FAM222B</i>) were identified and validated at both mRNA and protein levels. Elevated FAM50A expression was linked to advanced tumor stage, higher grade, and unfavorable prognosis. The constructed prognostic nomogram accurately predicted 1- and 3-year survival outcomes based on tumor stage, status, and <i>FAM50A</i> expression levels. Pathways enriched in <i>FAM50A</i> co-expressed genes included RNA processing, oxidative phosphorylation, and cell cycle regulation. Additionally, <i>FAM50A</i> expression was associated with immune cell infiltration and immune checkpoint activity. Knockdown of <i>FAM50A</i> led to the suppression of HCC cell proliferation, migration, and invasion.</p><p><strong>Conclusions: </strong>This study identifies five FAM genes with prognostic relevance in HCC, among which FAM50A emerges as a potential independent prognostic biomarker and therapeutic target.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4720-4747"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065422","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":"Influential factors affecting the survival benefit of combined neoadjuvant therapy and esophagectomy in patients with esophageal cancer: an analysis based on the SEER database.","authors":"Mi Chen, Li Jia, Zhou Su","doi":"10.21037/tcr-2025-543","DOIUrl":"10.21037/tcr-2025-543","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer (EC) is a major contributor to cancer-related deaths globally, with significant mortality rates. Neoadjuvant therapy (NAT), involving preoperative chemotherapy or radiation, aims to enhance outcomes in EC when combined with esophagectomy. However, its efficacy varies, necessitating identification of factors influencing survival benefits. This study aims to identify the factors influencing the survival benefit of NAT in patients with EC.</p><p><strong>Methods: </strong>The current retrospective cohort study collected data from the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2015. Propensity score matching (PSM) was used to balance baseline characteristics between the NAT and No NAT groups. A Cox model-based residual approach was applied to estimate the likelihood of survival benefit. Logistic regression was used to explore associated factors in the training cohort, and a nomogram was subsequently developed and validated.</p><p><strong>Results: </strong>In total, 2,755 patients were included in this study. Before PSM, the NAT group had a significantly longer median overall survival (mOS) than the No NAT group (31 <i>vs.</i> 21 months, P<0.001). After PSM, the survival advantage of the NAT group persisted (24 <i>vs.</i> 21 months, P=0.03). In the training cohort, tumor (T) stage, metastasis (M) stage, tumor grade, and lymph node ratio (LNR) appeared to be associated with survival benefit among patients receiving NAT. A nomogram was subsequently constructed based on these factors to estimate the likelihood of deriving benefit from NAT. In the validation cohort, the model exhibited reasonable discriminatory performance, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.782.</p><p><strong>Conclusions: </strong>This study identified clinical features potentially associated with survival benefit from NAT in patients with EC. The nomogram may serve as a reference tool to support treatment planning and patient selection in clinical practice.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4837-4850"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065492","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":"RHOJ enhances adhesion and proliferation capabilities and suppresses apoptosis of melanoma cells by activating the Rap1 signaling pathway.","authors":"Xi He, Jie Ma, Jiali Xia, Zhiqiang Guan, Guan Jiang","doi":"10.21037/tcr-2024-2692-b","DOIUrl":"10.21037/tcr-2024-2692-b","url":null,"abstract":"<p><strong>Background: </strong>Melanoma is an aggressive skin cancer derived from melanocytes, known for its high metastatic potential and poor prognosis. Understanding the molecular mechanisms underlying melanoma progression could provide novel therapeutic targets for improving treatment outcomes. Our study aims to investigate the role of the RHO family GTPase RHOJ in melanoma progression and its regulation of cell adhesion, proliferation, and apoptosis through the Rap1 signaling pathway.</p><p><strong>Methods: </strong>The Gene Expression Omnibus (GEO) dataset GSE122907 and the Gene Expression Profiling Interactive Analysis (GEPIA) database were used to analyze differentially expressed genes related to melanoma. A375 cells were employed as the in vitro melanoma model. The STRING database was utilized to identify RHOJ-associated genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed based on these genes. A375 cells were transfected with si-RHOJ, with or without the addition of a Rap1 signaling pathway activator. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay, while cell proliferation was measured using the 5-ethynyl-2'-deoxyuridine (EdU) assay. Apoptosis was evaluated by flow cytometry, and cell adhesion was determined using a cell adhesion detection kit. The expression of relevant genes was analyzed by real-time polymerase chain reaction (PCR), Western blot, and immunofluorescence techniques.</p><p><strong>Results: </strong>RHOJ, a key differentially expressed gene associated with melanoma, was significantly upregulated in melanoma cells, particularly in A375 cells. Knockdown of RHOJ reduced cell viability and proliferation, increased cell apoptosis, upregulated Bax, and downregulated Bcl-2. Additionally, cell adhesion was diminished, accompanied by the upregulation of E-cadherin and the downregulation of vinculin. The Rap1 signaling pathway was identified as a key pathway regulated by RHOJ. The levels of RAP1, RAP1GAP, and RasGRP3 were decreased in A375 cells transfected with si-RHOJ; however, these changes were reversed by activation of the Rap1 signaling pathway. Moreover, we found that the Rap1 signaling pathway activator could reverse the reduction in cell viability, proliferation, and adhesion, as well as the increase in apoptosis induced by si-RHOJ.</p><p><strong>Conclusions: </strong>In conclusion, RHOJ promotes melanoma cell adhesion and proliferation while inhibiting apoptosis through the activation of the Rap1 signaling pathway, highlighting the potential clinical implications of targeting RHOJ in melanoma treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4822-4836"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065624","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 into the sensitivity of adipocytes mediated by the major vault protein (MVP) to chemotherapy for triple-negative breast cancer.","authors":"Lianjin Qin, Ruofan Fei, Wenjuan Wang, Qingjian He","doi":"10.21037/tcr-2025-1175","DOIUrl":"10.21037/tcr-2025-1175","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy is an important therapeutic method for treating triple-negative breast cancer (TNBC), and docetaxel is the most commonly used chemotherapy drug for TNBC. Fat cells may increase the aggressiveness of TNBC and reduce the therapeutic effect of docetaxel. This research aimed to examine the mechanisms underlying the reduced chemosensitivity of TNBC to docetaxel.</p><p><strong>Methods: </strong>Cell migration and invasion experiments revealed that breast cancer cells cocultured with mature adipocytes had increased invasive and migratory capabilities, and decreased sensitivity to docetaxel chemotherapy. Immunofluorescence and Western blot analyses revealed the significant upregulation of major vault protein (MVP) expression in the cocultured breast cancer cells.</p><p><strong>Results: </strong>Our findings indicated that docetaxel effectively inhibited the proliferation, migration, and invasion of the MDA-MB231 cells. The optimal therapeutic concentration for the MDA-MB231 cells was 1,000 nM, and the optimal treatment duration was 48 hours.</p><p><strong>Conclusions: </strong>The level of MVP expression appears to influence the chemosensitivity of breast cancer cells to docetaxel. Notably, our results suggest that cocultured breast cancer cells may modulate MVP expression via the Notch1 signaling pathway. Overall, this study provides evidence that adipocytes could influence the chemosensitivity of TNBC cells to docetaxel via MVP expression.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"5109-5126"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065559","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 an immune-related gene signature for the prognostic and immune landscape prediction in head and neck squamous cell carcinoma by integrated analysis of machine learning and Mendelian randomization.","authors":"Zhengyu Wei, Guoli Wang, Yanghao Hu, Chongchang Zhou, Yuna Zhang, Yaowen Wang","doi":"10.21037/tcr-2024-2665","DOIUrl":"10.21037/tcr-2024-2665","url":null,"abstract":"<p><strong>Background: </strong>The immune microenvironment is pivotal in cancer advancement and reappearance. Nevertheless, the study concerning the association between immune-related genes (IRGs) and outcome in head and neck squamous cell carcinoma (HNSCC) is insufficient. This investigation sought to develop an IRG prediction model for accurately assessing the prognosis and immunological patterns in HNSCC.</p><p><strong>Methods: </strong>Gene expression and clinical information of HNSCC were obtained, including 522 HNSCC and 44 normal tissue specimens from The Cancer Genome Atlas and 270 HNSCC from the Gene Expression Omnibus GSE65858 database. By employing machine learning algorithms, an innovative prognostic IRG signature was established. This model allowed for calculating a risk score for each sample, thereby enabling the stratification of individuals into low-risk and high-risk cohorts. The prognostic significance of the signature was evaluated concerning survival, tumor mutation burden, immune cell infiltration, and its capacity to predict the response to immunotherapy. Subgroup analyses were performed based on age, sex, grade, and stage. Mendelian randomization (MR) was employed to assess the causative link between model gene expression and HNSCC development.</p><p><strong>Results: </strong>Ten IRGs were identified and incorporated into the predictive signature. The area under the receiver operating characteristic curves for overall survival at 1, 3, and 5 years were 0.694, 0.731, and 0.656, respectively. Kaplan-Meier survival analysis indicated that individuals in the high-risk cohort displayed substantially inferior outcomes versus those classified as low-risk. The multivariate prognostic analysis showed that the risk score was an independent prognostic factor associated with HNSCC (hazard ratio =3.647, P<0.001). Subgroup analyses stratified by clinical parameters demonstrated that the prognostic signature was consistently effective across all subgroups, underscoring its wide applicability. Additionally, individuals with low-risk demonstrated a more favorable prognosis, which was linked to heightened immunological scores, enhanced immune-related functioning, and increased immune cell infiltration. Moreover, low-risk patients responded better to immunotherapy than high-risk individuals. MR results suggested a causal relationship between CCR7 expression and HNSCC development.</p><p><strong>Conclusions: </strong>The IRG-related signature has been developed to predict survival results and immunological features of HNSCC. The model's robustness across various clinical subgroups, coupled with its capacity to predict responses to immunotherapy, highlights its potential for clinical application. This reliable prognostic signature has the ability to guide the development of novel therapeutic strategies for HNSCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4520-4538"},"PeriodicalIF":1.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065145","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}