Translational cancer research最新文献

{"title":"Most eligible candidates for primary tumor resection among metastatic colorectal cancer patients: a SEER-based population analysis.","authors":"Cheng-Wu Jin, Sun-Yuan Lv, Can Yang, Mao Tan, Vishal G Shelat, Peter C Ambe, Timothy Price, Li Song, Wei Peng, Shu-Lang Jian, Heng Liu","doi":"10.21037/tcr-2025-1084","DOIUrl":"10.21037/tcr-2025-1084","url":null,"abstract":"<p><strong>Background: </strong>Primary tumor resection (PTR) can improve the prognosis and survival of some patients with metastatic colorectal cancer (mCRC). However, selecting candidates that may benefit from this intervention may be challenging. Therefore, we aim to construct a predictive model to help identify the most eligible candidates for PTR.</p><p><strong>Methods: </strong>Propensity score matching (PSM) was used to balance the baseline characteristics of the patients. Patients in the surgical group were further allocated to either a beneficial or a non-beneficial cohort based on whether their survival time exceeded the median overall survival (mOS) time of the non-surgical group. A multivariate Cox analysis was then conducted to select independent prognostic risk factors the surgical group. Finally, multivariate logistic regression was used to establish a predictive model based on the demographic characteristics, and the calibration curves, area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and a decision curve analysis (DCA) were used to validate and assess the model accuracy and clinical prediction ability.</p><p><strong>Results: </strong>A total of 11,763 mCRC patients were enrolled in the study, of whom 8,808 (74.88%) underwent PTR. After PSM, the median cancer-specific survival (CSS) was 29 months in the surgical group and 16 months in the non-surgical group (P<0.001). Based on the logistic regression, 10 covariates [age, ethnicity, negative or positive CEA, TNM staging, grade, bone metastasis, liver metastasis, histology, primary tumor site, distant metastasis surgery (or no surgery), and chemotherapy] were identified and used to construct the predictive model, using a training and a validation group. The AUC values of the nomograph were 0.727 in the training group and 0.742 in the validation group. The calibration curves, DCA and Kaplan-Meier (K-M) analysis results suggest that the predictive model was able to accurately predict the likelihood of a patient benefiting from PTR (P<0.001).</p><p><strong>Conclusions: </strong>This study constructed and validated a predictive model to help clinicians identify patients with mCRC who are most likely to benefit from PTR.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4381-4398"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical pathological characteristics correlation of <i>H3F3A</i> gene mutation in giant cell tumor of bone: a study of 96 cases.","authors":"Juan Du, Siying Liu, Lei Miao, Huijun Yang, Jiayao Li, Fei Wang, Xuzhi Wang, Ningning Shen, Zhiqing Yang, Lifang Gao, Wenxia Ma, Chen Wang","doi":"10.21037/tcr-2024-2564","DOIUrl":"10.21037/tcr-2024-2564","url":null,"abstract":"<p><strong>Background: </strong>Giant cell tumor of bone (GCTB) has been a common primary bone tumor with potential malignancy and local aggressiveness. <i>H3F3A</i> gene mutation has been gradually understood to be related with GCTB occurrence. However, the relationship between different mutation sites and tumor pathological morphology as well as clinical prognosis is still uncertain. This study aimed to investigate the clinical pathological characteristics of GCTB and analyze the potential correlation between <i>H3F3A</i> and GCTB tumor recurrence and prognosis risk.</p><p><strong>Methods: </strong>A total of 96 cases of GCTB samples diagnosed by two registered pathologists in the Second Hospital of Shanxi Medical University from January 2019 to December 2023 were collected. The clinical and pathological features of the samples were evaluated by pathological hematoxylin and eosin (HE) staining combined with immunohistochemistry (IHC) experiments. <i>H3F3A</i> mutation status was analyzed based on Sanger sequencing. Further, the associations between <i>H3F3A</i> mutation sites and GCTB clinical features, especially recurrence risk, were explored.</p><p><strong>Results: </strong>Among the 96 GCTB cases, <i>H3F3A</i> was detected to be mutated in 85 cases (88.54%) with the main mutation site defined as <i>H3F3A</i> G34W (76 cases, 89.41%), and other relatively rare mutation sites including G34V, G34L, and Y41H. Of these sites, Y41H mutation was firstly reported in the study. Meanwhile, 15 of the 96 patients encountered recurrence, with clinicopathological features including the Campanacci grading system (which is based on imaging evaluation), tumor soft tissue invasion, P53 expression, and different mutation sites of <i>H3F3A</i> gene associated with tumor recurrence. In particular, compared with the common <i>H3F3A</i> G34W mutation, other relatively rare mutation sites were revealed to be correlated with increased intravascular tumor thrombin and higher tumor cell mitosis, and these patients tended to have a greater risk of recurrence.</p><p><strong>Conclusions: </strong>Multiple clinicopathological features of GCTB including Campanacci grading system, soft tissue invasion, and <i>H3F3A</i> mutation in rare gene sites were associated with tumor recurrence, and the cases with rare <i>H3F3A</i> mutation sites encountered recurrence more frequently than those with G34W mutation. It is of clinical significance to elucidate in detail the mutation sites of <i>H3F3A</i> by Sanger or high-throughput sequencing analysis.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4260-4278"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical value of SPP1 overexpression in patients with papillary thyroid carcinoma.","authors":"Linfeng Xin, Changqing Li, Hui Ni, Guangcheng Fu, Qin Qin, Lin Zhang","doi":"10.21037/tcr-2024-2568","DOIUrl":"10.21037/tcr-2024-2568","url":null,"abstract":"<p><strong>Background: </strong>Secreted phosphoprotein 1 (SPP1) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family. SPP1 is known to be involved in various cancer-related signaling pathways. Nevertheless, limited research has been conducted on the association between SPP1 and papillary thyroid carcinoma (THCA). This study aimed to investigate the expression of SPP1 in papillary THCA and its relationship with clinical relevance and immune cell infiltration.</p><p><strong>Methods: </strong>The expression and prognosis of SPP1 in pan-cancer were analyzed using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data plat forms. The differential expression of SPP1 between thyroid cancer and adjacent normal tissues was analyzed by the University of Alabama at Birmingham Cancer Data Analysis portal (UALCAN) online database. Thyroid cancer tissues and adjacent tissues were distinguished by the receiver operating characteristic (ROC) curve. The relationship between SPP1 and the signal pathway was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The correlation between SPP1 and immune cell infiltration was analyzed using the Tumor Immune Estimation Resource (TIMER). The correlation between the expression level of SPP1 detected by immunohistochemistry and the clinical characteristics, laboratory parameters, and inflammatory indexes of patients with papillary THCA in our center was verified.</p><p><strong>Results: </strong>TCGA and GTEx analyses showed that SPP1 was highly expressed in thyroid cancer compared with adjacent tissues, and was related to race, cancer stages, and pathological subtypes. The area under the curve (AUC) of the ROC curve was 0.668 for distinguishing SPP1 expression levels in normal and malignant thyroid tissues. The TIMER database showed that SPP1 expression was positively correlated with B cells, CD4⁺ T cells, neutrophils, macrophages, and dendritic cells (DC). GO and KEGG pathway analyses showed that SPP1 co-expressed genes were involved in the process of a variety of immune responses and diseases. Immunohistochemical results showed that the positive expression of SPP1 in papillary THCA was higher than that in adjacent tissues and correlated with Tumor-Capsule Distance Status, red blood cell distribution width variation coefficient (RDW-CV), platelet distribution width (PDW), mean platelet volume (MPV), large platelet ratio (P-LCR), mean corpuscular volume (MCV), and mean corpuscular-hemoglobin (MCH), and neutrophil-platelet ratio (NPR).</p><p><strong>Conclusions: </strong>In papillary THCA, elevated SPP1 expression correlates with clinicopathological features, suggesting its potential as a diagnostic marker.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4100-4114"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822688","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":"IL-6 promotes metastasis and EMT of non-small cell lung cancer cells by up-regulating FGL1 via STAT3 pathway.","authors":"Jing Liu, Qiuge Liu, Wenjing Qian, Chengguo Zong, Ruoyu Wang","doi":"10.21037/tcr-2025-119","DOIUrl":"10.21037/tcr-2025-119","url":null,"abstract":"<p><strong>Background: </strong>It has been reported that IL-6 induces the synthesis and secretion of fibrinogen-like protein 1 (FGL1) in liver cells as well as promotes the regeneration of liver cells. FGL1 is upregulated in human cancers, especially in non-small cell lung cancer (NSCLC). FGL1 is involved in the regulation of epithelial-mesenchymal transition (EMT) in gastric cancer (GC) cells. However, the role of IL-6/FGL1 signaling axis in the EMT process of NSCLC cells and its mechanism remain unclear. In this study, we investigated the role of FGL1 in mediating the metastasis and EMT processes of NSCLC cells, as well as the underlying signaling mechanisms.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) database and STARBASE database were used to analyze the biological information of FGL1 gene expression in NSCLC patients, and the database information was verified by clinical data. Transwell, Western blotting and microscopy were used to observe the effects of FGL1 on the metastasis and proliferation of NSCLC cells and the occurrence of EMT and its potential signaling pathway proteins.</p><p><strong>Results: </strong>Database analysis and clinical data showed that the prognosis of NSCLC patients with high FGL1 expression was poor. Cell phenotypic experiments showed that FGL1 silencing significantly reduced proliferation, migration and EMT of NSCLC cells, suggesting that the expression level of FGL1 may be significantly correlated with migration ability and EMT in lung cancer cells. In addition, the FGL1-neutralizing antibody inhibited EMT and metastasis of NSCLC cells <i>in vivo</i>. Further studies showed that IL-6 may mediate EMT by inducing FGL1 expression through the STAT3 pathway in lung cancer cells. Furthermore, treatment with a STAT3 inhibitor significantly inhibited the IL-6-induced FGL1 expression and EMT in NSCLC cells.</p><p><strong>Conclusions: </strong>IL-6 regulates FGL1 expression to mediate metastasis and EMT of NSCLC cells through the STAT3 signaling pathway.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"3973-3990"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822696","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":"Integrative analysis of CRISPR screening and gene expression data identifies a three-gene prognostic model associated with immune microenvironment in neuroblastoma.","authors":"Xin Li, Wanrong Li, Jian Wang","doi":"10.21037/tcr-2024-2472","DOIUrl":"10.21037/tcr-2024-2472","url":null,"abstract":"<p><strong>Background: </strong>Neuroblastoma is a heterogeneous pediatric tumor with variable clinical outcomes. Current prognostic markers are insufficient to predict patient survival accurately, necessitating the identification of novel biomarkers and therapeutic targets. This study aimed to develop a robust prognostic model by integrating CRISPR screening data and transcriptomic profiles, and to explore its correlation with the tumor immune microenvironment.</p><p><strong>Methods: </strong>We integrated Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screening data from the DepMap database (version 24Q2) and gene expression profiles from neuroblastoma patients to identify key genes associated with neuroblastoma prognosis. Essential genes with Computational Evaluation of RNAi Essentiality Scores (CERES) scores less than -1 in at least 80% of 34 neuroblastoma cell lines were intersected with differentially expressed genes (|logFC| >2, P<0.05) from the National Genomics Data Center (NGDC) dataset (accession code HRA002064), resulting in 43 overlapping genes. Random forest analysis and multivariate Cox regression were conducted on the GSE49710 training set (n=498) to construct a prognostic model. The model was externally validated using the E-MTAB-8248 dataset (n=223). Immune infiltration and immunotherapy response were assessed using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE), Microenvironment Cell Populations counter (MCPcounter), Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT), immunophenoscore (IPS), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms.</p><p><strong>Results: </strong>A three-gene prognostic model comprising <i>PKMYT1</i>, <i>CDT1</i>, and <i>NCAPG</i> was established. Patients were stratified into high-risk and low-risk groups based on the median RiskScore of 9.514526. In the training set, high-risk patients exhibited significantly poorer overall survival compared to low-risk patients (log-rank test, P<0.001). The model outperformed traditional clinical factors and demonstrated consistent prognostic value in the external validation cohort. High-risk patients showed lower immune cell infiltration, higher TIDE scores, and lower IPS values, suggesting an immunosuppressive microenvironment and reduced likelihood of responding to immunotherapy. In contrast, low-risk patients had higher immune infiltration and a predicted immunotherapy response rate of 70% versus 36% in the high-risk group.</p><p><strong>Conclusions: </strong>The three-gene prognostic model effectively stratifies neuroblastoma patients by survival risk and correlates with immune microenvironment characteristics. This model has potential clinical utility for prognosis prediction and guiding personalized immunotherapy strategies in neuroblastoma.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4058-4070"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822699","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":"Metabolomic profiling for predicting breast cancer treatment toxicities.","authors":"Jennifer J Hu, Alexandra N McMahon, Yawen Lu, Veronica Z Paley","doi":"10.21037/tcr-2025-261","DOIUrl":"10.21037/tcr-2025-261","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"3883-3886"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822677","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":"Association between real-time shear wave elastography findings and HER-2 expression in breast cancer.","authors":"Ying He, Qi Zhang, Yuwei Zeng, Danni Zhu, Jienv Lou, Dan Mao","doi":"10.21037/tcr-2024-2359","DOIUrl":"10.21037/tcr-2024-2359","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor-2 (HER-2) overexpressing breast cancer is associated with more aggressive tumor characteristics and poorer clinical outcomes. It is important to determine HER-2 status of breast cancer for better treatment planning. This study aims to explore the correlation between real-time shear wave elastography (SWE) and HER-2 expression in breast cancer.</p><p><strong>Methods: </strong>A total of 67 patients who underwent breast cancer surgery between January 2017 and January 2021 were recruited for this retrospective study. Among 70 breast cancer lesions in the included patients, 31 lesions were HER-2 negative, and 39 lesions were HER-2 positive. SWE imaging was conducted and Young's modulus values including mean elastic modulus (E_mean), maximum elastic modulus (E_max), and minimum elastic modulus (E_min) were measured. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of the imaging parameters for HER-2 positivity.</p><p><strong>Results: </strong>The HER-2 positive group had a higher proportion of lesions with a diameter of ≥20 mm. The E_max value was significantly lower in the HER-2 positive group compared to the negative group (P<0.05). The highest area under the curve (AUC) value (0.800) was observed for the combination of E_max, lesion size, and calcification, with a sensitivity of 66.7% and specificity of 83.9%.</p><p><strong>Conclusions: </strong>E_max combined with lesion size and calcification showed a moderate association with HER-2 positivity, suggesting a potential role for SWE in complementing established diagnostic methods. These findings suggest that SWE parameters, in particular E_max may be useful in the non-invasive assessment of HER-2 status in breast cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4071-4079"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822685","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 safety and efficacy of NEPA in preventing postoperative nausea and vomiting after general anesthesia during gastrointestinal cancer surgery: a single-center retrospective study.","authors":"Yinchao Zhang, Chao Li, Linze Xu, Jin Zhang, Dandan Wu, Yu Bai, Huikai Li","doi":"10.21037/tcr-2024-2193","DOIUrl":"10.21037/tcr-2024-2193","url":null,"abstract":"<p><strong>Background: </strong>Postoperative nausea and vomiting (PONV) are common complications after gastrointestinal (GI) tumor surgery under general anesthesia that hinder recovery. This retrospective study, conducted from May to September 2023 at Tianjin Cancer Hospital Airport Hospital, aimed to evaluate the safety and efficacy of netupitant and palonosetron (NEPA) in reducing PONV in such patients.</p><p><strong>Methods: </strong>All patients received one NEPA capsule orally the evening before surgery. PONV symptoms, including nausea, vomiting, pain, abdominal discomfort, and satiety, were monitored for 72 hours postoperatively via daily visual analog scale (VAS) score assessment.</p><p><strong>Results: </strong>We initially included 50 patients; 45 patients (32 males, 13 females) met the inclusion criteria, with an average body mass index (BMI) of 23.2±4.2 kg/m² and a mean weight of 66.2±13.2 kg. Within the first 24 hours post-surgery, 6 (14%) patients experienced vomiting, with 20% of these patients having a VAS score above 4; this proportion was 13% within 24-48 hours and decreased to only 4% within 48-72 hours. No vomiting was documented in the 48-72-hour postoperative period, and the incidence of vomiting in patients treated with NEPA was significantly lower than the guideline incidence.</p><p><strong>Conclusions: </strong>NEPA demonstrated high efficacy and convenience, with vomiting occurring in only 15% of patients and nausea in 40% within 72 hours after surgery and more patients showed a trend toward a favorable response over time. NEPA has proven to be a safe, effective, and convenient option for preventing PONV in GI cancer surgeries.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4369-4380"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822713","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 and validation of a novel signature based on M2 macrophage co-expressed genes in bladder cancer.","authors":"Xinyu Xu, Minyu Yan, Zhiwen Xie, Yongqing Zhang, Lei Wu, Bimeng Zhang, Juntao Jiang","doi":"10.21037/tcr-24-2013","DOIUrl":"10.21037/tcr-24-2013","url":null,"abstract":"<p><strong>Background: </strong>Extensive evidence has demonstrated a robust association between high infiltration of M2 macrophages and the prognosis of bladder cancer (BLCA). Nevertheless, no comprehensive analysis of co-expressed M2 genes in BLCA has been reported. We would like to develop a prognostic model for BLCA using M2 co-expressed genes.</p><p><strong>Methods: </strong>Raw data and clinical characteristics were retrieved from public databases. We first used the \"cibersort\" package to determine the M2 macrophage infiltration coefficients of each BLCA sample in The Cancer Genome Atlas (TCGA). Subsequently, Pearson correlation was employed to screen co-expressed genes based on the coefficients. Least absolute shrinkage and selection operator (LASSO-COX) analysis was then employed to construct the prognostic gene signature, which was externally validated in the GSE13507 cohort. Further exploration of the signature involved tumor mutational burden (TMB) and drug sensitivity analyses. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to validate the expression levels of the co-expressed genes.</p><p><strong>Results: </strong>We developed a signature using two co-expressed genes and utilized it to categorize samples into two groups. Patients in the low-risk group exhibited more satisfactory outcomes (P=0.008) and higher TMB (P=0.04). Additionally, the high-risk group exhibited a substantial discrepancy in immune subtypes compared to the low-risk group, as indicated by the significantly elevated levels of resting CD4 memory T cells, M0, and M2.</p><p><strong>Conclusions: </strong>We constructed a prognostic signature for BLCA based on two co-expressed genes. The performance of this signature was validated in both TCGA and GSE13507, indicating its potential usefulness in predicting the prognosis of BLCA and developing new therapeutic methods.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"4194-4207"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822693","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 and validation of hub genes for kidney renal clear cell carcinoma treated with metformin and everolimus combination therapy.","authors":"Shenbao He, Bin Zhang, Lili Zhang, Panfeng Shang, Zhongjin Yue","doi":"10.21037/tcr-2025-277","DOIUrl":"10.21037/tcr-2025-277","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Renal cell carcinoma (RCC) is a prevalent malignancy of the urinary system that presents significant health and economic burdens. Despite existing treatments such as surgery and targeted therapies, challenges remain due to suboptimal efficacy and high recurrence rates. Previous studies have indicated that metformin and everolimus individually exhibit inhibitory effects on RCC. However, their synergistic potential when combined has not been fully elucidated. Therefore, this paper identified the antiproliferative effect and the hub genes that undergo significant changes in 786-O cells when treated with the combination drugs and their underlying mechanisms to inform the search for kidney renal clear cell carcinoma (KIRC) therapeutic targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The effects of the combination of metformin and everolimus on 786-O cells viability, migration and invasion were investigated. Differentially expressed genes (DEGs) among different drug treatment groups were identified through ribonucleic acid (RNA) sequencing, raw data processing and differential expression analysis. The target genes were obtained by taking the intersection of different DEGs, and hub genes were identified by Maximal Clique Centrality (MCC) and Molecular Complex Detection (MCODE) algorithms, expression validation, and Kaplan-Meier (K-M) survival curve plotting. Subsequently, transcription factors (TFs) regulating the hub genes were identified and drug-hub gene interactions were explored through molecular docking. In addition, gene set enrichment analysis (GSEA) demonstrated hub gene-related biological functions and pathways, and gene set variation analysis (GSVA) explored differential pathways between different drug treatment groups. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression difference of hub genes among four groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The combination of metformin and everolimus is more effective than monotherapy at inhibiting cell viability, migration, and invasion in 786-O cells. In total, 3,030 DEG1, 2,953 DEG2, 3,591 DEG3, 1,571 DEG4 and 4,064 DEG5 were identified, yielding five target genes. After MCC and MCODE algorithms, expression validation, and K-M survival curve plotting, target genes were all noted as hub genes (&lt;i&gt;SPC25&lt;/i&gt;, &lt;i&gt;NCAPH&lt;/i&gt;, &lt;i&gt;MCM10&lt;/i&gt;, &lt;i&gt;UHRF1&lt;/i&gt;, &lt;i&gt;SMC4&lt;/i&gt;). Eleven TFs regulated more than two hub genes, and the binding energy of metformin with &lt;i&gt;SPC25&lt;/i&gt; and everolimus with &lt;i&gt;SMC4&lt;/i&gt; was the lowest. Hub genes were negatively correlated with lysosome and positively associated with cell cycle, and the P13K/Akt/mTOR signaling pathway was significantly positively correlated with hub genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Metformin and everolimus are synergistic in anticancer effects on RCC. Based on transcriptomic data, this study obtained five hub genes associated with everolimus and metformin combination therapy in ","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 7","pages":"3943-3960"},"PeriodicalIF":1.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822695","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}