Translational cancer research最新文献

{"title":"Low expression of PRTN3 regulates the progression of gastric cancer by inhibition of cell cycle and promotion of apoptosis.","authors":"Haoyu Zhu, Fei Wang, Xinran Lu, Hao Wu, Chao Shi, Silvio Matsas, Renata D'Alpino Peixoto, Marcelo Porfirio Sunagua Aruquipa, Chong Tang, Shichun Feng","doi":"10.21037/tcr-2025-153","DOIUrl":"10.21037/tcr-2025-153","url":null,"abstract":"<p><strong>Background: </strong>Proteinase 3 (PRTN3) has been linked to the progression of different cancer types. In this study, the expression and cell biological function of PRTN3 were investigated in gastric cancer (GC) to assess its role in GC progression.</p><p><strong>Methods: </strong>The PRTN3 levels in 20 pairs of GC tissues were detected via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting, while immunohistochemical staining was used to assess the PRTN3 levels in 47 GC tissue samples. The effects of stable lentivirus-mediated PRTN3 knockdown on GC cell proliferative, cell cycle, and apoptotic activity were evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays, nude mouse models, and flow cytometry.</p><p><strong>Results: </strong>Elevated levels of PRTN3 messenger RNA (mRNA) and protein were noted in GC tissues, mostly in the cytosol. High PRTN3 levels were positively correlated with GC tumor N staging. <i>in vitro</i> knockdown of PRTN3 suppressed cell cycle progression, promoted apoptotic induction, and decreased the concentrations of cell cycle-associated proteins (cyclin D1, CDK4, and CDK6) and apoptosis-related Bcl-2 while inducing the upregulation of Bax. Downregulation of PRTN3 inhibited GC cell growth both <i>in vitro</i> and in mouse models.</p><p><strong>Conclusions: </strong>Our study found that high expression of PRTN3 is associated with GC tumor N staging. And PRTN3 silencing could regulate GC progression by inhibiting the cell cycle and promoting apoptosis in GC cells, which could be a potential target for GC diagnosis and treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1415-1427"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657929","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":"Amyopathic dermatomyositis associated with immune checkpoint inhibitor therapy in lung adenocarcinoma: a case report.","authors":"Zhang Zhang, Takehiro Uemura, Pengyi Guo","doi":"10.21037/tcr-2024-2364","DOIUrl":"10.21037/tcr-2024-2364","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have proven efficacious in various types of cancers, including lung cancer, but they usually lead to a set of organ-specific immune-related adverse events (irAEs). In particular, checkpoint inhibitor pneumonitis (CIP) requires special attention because it is difficult to diagnose and can be potentially fatal. Accumulating real-world epidemiological data indicate that CIP is more common than previously reported. Amyopathic dermatomyositis (ADM), which shows no or minimal muscle damage, is positive for anti-melanoma differentiation-associated gene 5 (anti-MDA5) and involves unique skin findings, as well as clinical features of rapidly progressive interstitial lung disease (RP-ILD). Therefore, knowing how to differentiate between CIP and ADM-related RP-ILD is important, which can provide valuable experience for subsequent treatment of patients.</p><p><strong>Case description: </strong>We report a case of a patient with stage IV lung adenocarcinoma who developed ADM associated with RP-ILD following the administration of pembrolizumab, an inhibitor of the programmed cell death 1 (PD-1) pathway. The principal adverse reactions to pembrolizumab are irAEs. However, pembrolizumab-associated ADM has not been previously reported in clinical settings. The patient presented with atypical skin lesions and tested positive for anti-MDA5 antibodies, accompanied by severe acute ILD.</p><p><strong>Conclusions: </strong>We believe this case represents a valuable clinical reference for the future management of irAEs caused by pembrolizumab and emphasizes the necessity of early screening for anti-melanoma differentiation associated protein 5 (MDA5) antibodies in patients with CIP presenting as RP-ILD.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1500-1505"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658431","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 causal effects of 2,821 protein level ratios on non-small cell lung cancer: a two-sample Mendelian randomization study.","authors":"Xinyun Zou, Jinlan Shen, Xiaokai Li, Yong Diao, Ling Zhang","doi":"10.21037/tcr-24-1523","DOIUrl":"10.21037/tcr-24-1523","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) has a complex etiology, making early diagnosis difficult and leading to high mortality rates, thus necessitating personalized treatment strategies. While protein level ratios have shown potential as biomarkers or therapeutic targets, their causal relationship with NSCLC remains unclear. This study aimed to investigate these causal links using Mendelian randomization (MR), providing insights into potential biomarkers and therapeutic avenues.</p><p><strong>Methods: </strong>We executed an intricate two-sample MR study to explore the stochastic causal links between 2,821 protein level ratios and NSCLC. The genome-wide association study (GWAS) statistics for NSCLC and protein level ratios were sourced from the Finnish Database (version 10) and the UK Biobank, respectively. For the instrumental variables (IVs) related to protein level ratios, we selected IVs with a P value <1.0×10^-5. Throughout this analysis, we applied five established MR techniques.</p><p><strong>Results: </strong>Our study identified causal relationships between 142 protein level ratios and NSCLC. Notably, the AKR1B1/SUGT1 protein level ratio and the PLPBP/STIP1 protein level ratio demonstrated the most significant negative correlations with NSCLC risk. On the other hand, the ARHGEF12/IRAK4 protein level ratio and the BANK1/LBR protein level ratio exhibited the most significant positive correlations. Furthermore, sensitivity analyses did not reveal any significant heterogeneity or horizontal pleiotropy.</p><p><strong>Conclusions: </strong>Studying specific protein level ratios in patients can reveal the molecular mechanisms and pathological processes of NSCLC, which has certain clinical significance for early diagnosis of NSCLC, understanding drug resistance mechanisms and developing personalized treatment strategies. However, these findings necessitate further validation through extensive clinical research.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1101-1110"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658617","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 prediction model for overall survival in correlation between butyrate metabolism and gastric cancer prognosis: Mendelian randomization and transcriptomics analysis.","authors":"Renjun Gu, Kun Mei, Zilu Chen, Yan Huang, Fangyu Wang","doi":"10.21037/tcr-24-677","DOIUrl":"10.21037/tcr-24-677","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) remains a leading cause of cancer-related mortality due to its late diagnosis and poor prognosis. Butyrate metabolism (BM) has demonstrated significant roles in tumor biology, but its prognostic implications in GC remain unexplored. We aimed to investigate the effect of butyrate metabolic biomarkers on the prognosis of GC.</p><p><strong>Methods: </strong>We acquired datasets from The Cancer Genome Atlas and Gene Expression Omnibus. Differential BM-related genes (BMGs) were identified using weighted gene co-expression network analysis (WGCNA). Patients were stratified into subtypes, and a prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression. Mendelian randomization (MR) analysis was conducted using genetic variants as instrumental variables to establish causal links between BM and GC prognosis.</p><p><strong>Results: </strong>Our model demonstrated robust prognostic accuracy with an area under the receiver operating characteristic (ROC) curve of 0.716. Transcriptomic analysis identified two key BMGs, SMC2 and HSPB1, with significant implications for GC survival. However, MR analysis provided no evidence of a causal association between BM and GC.</p><p><strong>Conclusions: </strong>We identified two butyrate metabolic prognostic genes, namely, structural maintenance of chromosome 2 and heat shock protein beta-1, as the prognostic markers for GC. Furthermore, MR indicated no causal association between the butyrate metabolic pathway and GC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"743-760"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658714","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":"Total Astragalus saponins promote ferroptosis in gastric cancer cells by upregulating SIRT3.","authors":"Yue Zou, Jingling Zhao, Chengyin Li, Rui Wang, Xiaocui Jiang, Zhongyi Zhu, Qiyuan Wang, Min Xiao","doi":"10.21037/tcr-24-1421","DOIUrl":"10.21037/tcr-24-1421","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a malignant tumor of the digestive tract originating from the epithelial cells of the gastric mucosa, which is highly invasive and heterogeneous, posing a serious threat to human health. In recent years, ferroptosis, as a novel mode of programmed cell death, has shown potential anticancer effects in tumor therapy. Total Astragalus saponins (TAS), a natural product derived from Astragalus membranaceus, have been shown to possess various pharmacological activities, including anticancer effects. This study aimed to investigate the effects of TAS on GC cells, focusing on the mechanism of action of its regulation of the silent information regulator 3 (SIRT3) in inducing ferroptosis in GC cells.</p><p><strong>Methods: </strong>We treated SGC-7901 cells with TAS at concentrations of 50, 100, and 200 µg/mL. After TAS treatment, the SGC-7901 cells were transfected with a vector designed to knock down SIRT3 expression. We assessed cell proliferation, viability, and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay), colony formation assay, and flow cytometry. SIRT3 expression was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fe²⁺, malondialdehyde (MDA), lactate dehydrogenase (LDH), and superoxide dismutase assay kits were used to detect the level of reactive oxygen species (ROS) by fluorescent probe assay. Western blot was used to detect apoptosis-related proteins and SIRT3 protein expression.</p><p><strong>Results: </strong>TAS dose-dependently inhibited SGC-7901 cell proliferation and viability (P<0.05) and induced apoptosis (P<0.05). TAS promoted the expression of SIRT3 and ACSL4 proteins (P<0.05), inhibited the expression of SLC7A11 and GPX4 proteins (P<0.05), and induced ferroptosis of SGC-7901 cells (P<0.05). Knockdown of the SIRT3 gene attenuated the effect of TAS treatment on ferroptosis (P<0.05).</p><p><strong>Conclusions: </strong>TAS has therapeutic potential for GC and can effectively inhibit the proliferation and viability of SGC-7901 cells, and the mechanism may be that TAS upregulates SIRT3 to promote the ferroptosis of SGC-7901 cells.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1311-1322"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658734","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":"Mitochondrial permeability transition drives the expression, identification and validation of necrosis-related genes in prognostic risk models of hepatocellular carcinoma.","authors":"Jiaxuan Jin, Mengyuan Wang, Yinuo Liu, Wei Li, Xuemei Zhang, Zhuoxin Cheng","doi":"10.21037/tcr-24-1442","DOIUrl":"10.21037/tcr-24-1442","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, and the current treatment methods exhibit various limitations. In recent years, the role of mitochondrial permeability transition-driven necrosis-related genes (MPT-DNRGs) in the pathogenesis and progression of severe diseases, particularly tumors, has garnered significant attention. This study aimed to identify new targets and concepts for MPT-DNRG-targeted therapy in HCC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we utilized HCC-related datasets and MPT-DNRGs to identify differentially expressed genes (DEGs) between HCC patients and control groups. By conducting a cross-analysis of the results of DEGs and MPT-DNRGs, we screened candidate genes. Subsequently, univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis methods were employed to identify prognostic genes, which were used to construct a risk model and calculate individual risk scores for HCC patients. Additionally, we performed univariate and multivariate Cox regression analyses to identify independent prognostic factors and constructed a column chart based on these factors to predict the survival probability of HCC patients. Furthermore, gene set enrichment analysis (GSEA), the immune microenvironment, chemotherapy drugs, and the expression of prognostic genes between the two groups were analyzed. Finally, the expression of these prognostic genes was further confirmed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In this study, we identified 8,515 DEGs between HCC and control samples. By performing intersection analysis between DEGs and MPT-DNRGs, we pinpointed 15 candidate genes. Subsequently, through univariate Cox regression and LASSO regression analysis, we identified six genes (&lt;i&gt;LMNB2&lt;/i&gt;, &lt;i&gt;LMNB1&lt;/i&gt;, &lt;i&gt;BAK1&lt;/i&gt;, &lt;i&gt;CASP7&lt;/i&gt;, &lt;i&gt;LMNA&lt;/i&gt;, and &lt;i&gt;AKT1&lt;/i&gt;) that were significantly associated with overall survival (OS) in patients. Based on the median risk score, we categorized HCC patients into high-risk and low-risk groups. Kaplan-Meier (KM) survival analysis results demonstrated a significant difference in OS between the two groups, which was further validated through additional assessment. Furthermore, we constructed a nomogram to predict the survival probability of HCC patients. Moreover, GSEA revealed a crucial correlation between these genes and HCC, and highlighted a close association between risk scores and regulatory T cells. We also identified four chemotherapy drugs related to HCC. Finally, in both the training and validation cohorts, &lt;i&gt;LMNB2&lt;/i&gt;, &lt;i&gt;LMNB1&lt;/i&gt;, and &lt;i&gt;LMNA&lt;/i&gt; exhibited high expression levels in tumor samples. Further validation using RT-qPCR confirmed that the expression of all prognostic genes was significantly higher in HCC group compared to the control group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study explored six progn","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"1037-1052"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658018","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":"A prognostic model for laryngeal squamous cell carcinoma based on the mitochondrial metabolism-related genes.","authors":"Wei-Ming Hu, Wen-Jing Jiang","doi":"10.21037/tcr-24-1436","DOIUrl":"10.21037/tcr-24-1436","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial metabolism-related genes (MMRGs) have emerged as potential therapeutic targets in cancer. This study aimed to construct a prognosis model based on MMRGs for patients with laryngeal squamous cell carcinoma (LSCC).</p><p><strong>Methods: </strong>Differentially expressed MMRGs in LSCC were identified from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB). Their functions were characterized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A prognostic model was established using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses, and its performance was evaluated using Kaplan-Meier and receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA) was performed to elucidate the biological pathways associated with the hub prognostic MMRGs. Genetic perturbation similarity analysis (GPSA) was used to determine the regulatory network of hub genes. Additionally, the correlation of the hub MMRGs with the immune microenvironment and drug sensitivity was investigated.</p><p><strong>Results: </strong>We identified 308 differentially expressed MMRGs, enriched in various metabolic processes and pathways. The prognostic model comprising four hub MMRGs (<i>POLD1</i>, <i>PON2</i>, <i>SMS</i>, and <i>THEM5</i>) accurately predicted patient outcomes, with the high-risk group exhibiting poorer survival. Additionally, high expression of <i>POLD1</i> and <i>THEM5</i> while low expression of <i>PON2</i> and <i>SMS</i> indicated better prognosis for LSCC patients. GSEA revealed pathways correlated with each prognostic MMRG, such as PI3K-AKT-mTOR signaling pathways, while GPSA identified key regulatory genes interacting with four hub MMRGs. Furthermore, differences in the tumor immune microenvironment and somatic mutation profiles were observed between high- and low-risk groups. Finally, the correlation of four hub MMRGs with 30 drug sensitivity was revealed.</p><p><strong>Conclusions: </strong>This study highlights the prognostic significance of MMRGs in LSCC and underscores their potential as biomarkers for LSCC therapy.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"966-979"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658324","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":"To be or low TMB (tumor mutational burden).","authors":"Markus Falk, Markus Tiemann, Joachim H Ficker, Wolfgang M Brueckl","doi":"10.21037/tcr-24-1916","DOIUrl":"10.21037/tcr-24-1916","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"667-669"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658730","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":"<i>FUT10</i> is related to the poor prognosis and immune infiltration in clear cell renal cell carcinoma.","authors":"Yuqi Zhang, Ke Cui, Rong Qiang, Lin Wang","doi":"10.21037/tcr-24-449","DOIUrl":"10.21037/tcr-24-449","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC), is highly metastatic with unfavorable oncologic outcomes. The metastatic dissemination and underlying mechanisms of ccRCC remain insufficiently understood. The expression of fucosyltransferases (FUTs) has been explored in multiple cancer types, which affect survival of tumor cells and oncology progress. However, the role of fucosyltransferase 10 (<i>FUT10</i>), a member of the FUT family, is still unclear in ccRCC. We aimed to investigate the effects of <i>FUT10</i> on the prognosis and immune infiltration of ccRCC via The Cancer Genome Atlas (TCGA) database.</p><p><strong>Methods: </strong>The relationship between <i>FUT10</i> expression and clinical-pathologic features was evaluated by Welch's t-test, Wilcoxon signed-rank test, Dunn's test, and logistic regression based on TCGA datasets. The <i>FUT10</i> expression level was converted into a categorical variable by receiver operating characteristic (ROC) and the area under the curve (AUC). The factors associated with the prognosis were determined by Kaplan-Meier method. The function of <i>FUT10</i> was identified by functional enrichment analysis, gene set enrichment analysis (GSEA), gene correlation analysis, and immune infiltration analysis. At last, we verified the <i>FUT10</i> messenger RNA (mRNA) expression in ccRCC and adjacent kidney tissues by quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>Downregulated <i>FUT10</i> expression in ccRCC was associated with the clinical stage (P<0.001), T stage (P<0.001), M stage (P<0.001), and overall survival (OS) event (P<0.001). The ROC curve suggested that <i>FUT10</i> had a certain accuracy in the diagnostic ability in ccRCC (AUC =0.787). It was shown that patient survival was prolonged in the <i>FUT10</i> high-expression group. Meanwhile, multivariate analysis displayed that <i>FUT10</i> was an independent risk factor for ccRCC patients (P=0.003). Moreover, we uncovered that <i>FUT10</i> was involved in the phenotype of the immune response, oxidative phosphorylation (OXPHOS), arachidonic acid (AA) metabolism, and primary immunodeficiency (PID) by function enrichment analysis and GSEA. In addition, in the high <i>FUT10</i> expression group, natural killer (NK) CD56bright cells exhibited lower enrichment scores, and central memory T cells exhibited higher enrichment scores. Especially, <i>ARL8B</i>, a key factor in NK-mediated cytotoxicity, had a certain correlation with <i>FUT10</i> (r=0.590, P<0.001). Compared to the normal kidney tissues, the <i>FUT10</i> mRNA expression in the ccRCC was decreased (P=0.004).</p><p><strong>Conclusions: </strong><i>FUT10</i> might be a promising immune therapy target and prognostic biomarker in ccRCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"827-842"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657908","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":"Talin1 Ser425 phosphorylation promotes colorectal cancer progression and metastasis.","authors":"Zhengxiu He, Jian Sun, Mengmeng Wang, Shanshan Chen, Guoxin Mao, Li Yang","doi":"10.21037/tcr-24-1283","DOIUrl":"10.21037/tcr-24-1283","url":null,"abstract":"<p><strong>Background: </strong>Talin1 serves as a crucial element within the multiprotein adhesion complexes that facilitate processes such as cell migration, adhesion, and integrin signaling. This study aimed to explore the underlying role of Talin1 Ser425 phosphorylation in the development of colorectal cancer (CRC).</p><p><strong>Methods: </strong>Blank plasmids, non-phosphorylatable mutant Talin1 S425A plasmids, and phosphorylation-mimetic mutant Talin1 S425D plasmids were constructed and used for transfection of CRC cells. The expression of mRNA and protein in CRC cells or tumor tissues was assessed by The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UALCAN databases, immunohistochemistry (IHC), and Western blot (WB). Cell proliferation was assessed via 5-ethynyl-2-deoxyuridine (EDU) proliferation assay and colony formation assay. Cell migration and invasion were detected by wound healing assay and transwell assay. Cell apoptosis was assessed by flow cytometry. The Kaplan-Meier Plotter was used to evaluate the prognostic value of mRNA in CRC.</p><p><strong>Results: </strong>TLN1 was markedly downregulated in CRC tissues while the level of Talin1 Ser425 phosphorylation in CRC tissues and aggressive CRC cells was relatively higher. The S425A mutant inhibited CRC cell proliferation, migration, and invasion, whereas the S425D mutant promoted these processes. Flow cytometry assay showed that cell apoptosis was induced by S425A mutant and suppressed by S425D mutant in RKO cells. Further investigation suggested that CDK5 might be responsible for Talin1 phosphorylation.</p><p><strong>Conclusions: </strong>Talin1 Ser425 phosphorylation is of great importance in CRC development and Talin1 is supposed to be a potential tumor marker and therapeutic target for CRC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 2","pages":"796-807"},"PeriodicalIF":1.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658615","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}