Translational cancer research最新文献

{"title":"Ramifications of lymph node metastasis in patients with pT1 colorectal cancer.","authors":"Liming Wang, Pengchen Long, Yinggang Chen, Yasumitsu Hirano","doi":"10.21037/tcr-2024-2611","DOIUrl":"10.21037/tcr-2024-2611","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of stage IIIA colorectal cancer (CRC) is much better than stage II CRC in Japan. The purpose of this study was to investigate the implications of lymph node metastasis (LNM) in patients with pT1 CRC and to explore potential downstaging of pT1N1 CRC.</p><p><strong>Methods: </strong>This retrospective cohort study was undertaken at a high-volume cancer center in Japan, grouping all eligible patients with radically resected pT1 CRC (n=723) according to presence (LNM+) or absence (LNM-) of LNM. We compared relapse-free survival (RFS) and cancer-specific survival (CSS) rates before and after propensity score matching.</p><p><strong>Results: </strong>LNM was ultimately confirmed in 96 study subjects (13.3%). Ninety-two patients (95.83%) were N1 and only 4 (4.17%) patients were N2. Before matching, tumors of the LNM+ (<i>vs</i>. LNM-) group were bulkier (≥3 cm: 25.0% <i>vs</i>. 15.8%; P=0.03), with greater propensity for lymphatic (41.7% <i>vs</i>. 25.2%; P<0.001) or vascular (55.2% <i>vs</i>. 30.1%; P=0.004) invasion. Likewise, mean operative time (204.7±76.2 <i>vs</i>. 187.9±67.9; P=0.02) and hospital stay (10.47±9.449 <i>vs</i>. 8.32±7.029; P=0.03) tended to be lengthier. Although similar in terms of CSS (LNM+, 98.5%; LNM-, 99.0%; P=0.67), the LNM+ (<i>vs</i>. LNM-) group displayed significantly worse RFS (90.5% <i>vs</i>. 97.4%; P=0.004). After matching, neither RFS (94.8% <i>vs</i>. 90.2%; P=0.33) nor CSS (100% <i>vs</i>. 98.7%; P=0.23) differed significantly by group; and at no point (before or after matching) did LNM+ status emerge as an independent risk factor for RFS or CSS. Before matching, a higher recurrence rate was evident in the LNM+ (<i>vs</i>. LNM-) group (7.3% <i>vs</i>. 1.8%, P=0.001), but there was no difference in the matched groups.</p><p><strong>Conclusions: </strong>LNM does not affect the long-term survival of patients with pT1N1CRC after radical resection. Appropriate downstaging from stage IIIA may be a reasonable prospect for pT1N1CRC with a low recurrence factor.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3410-3419"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675771","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":"Retrospective prognostic evaluation and single-cell transcriptomic analyses of non-small cell lung carcinoma with malignant pleural effusion.","authors":"Peizhu Wu, Ran Gao, Kaikai Zhao, Xiangjiao Meng","doi":"10.21037/tcr-2024-2581","DOIUrl":"10.21037/tcr-2024-2581","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The impact of malignant pleural effusion (MPE) and intrapleural infusion therapy on the prognosis of non-small cell lung carcinoma (NSCLC) patients receiving immunochemotherapy remains unclear. Investigating the tumor microenvironment of MPE may offer valuable insights for improving outcomes, yet current research in this area is limited. The aim of this study is to explore the impact of MPE and intrapleural infusion therapy on prognosis in the era of immunochemotherapy, and to identify potential therapeutic targets for improving the prognosis of MPE patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study included advanced NSCLC patients without driver mutations who underwent first-line immunochemotherapy at Shandong Cancer Hospital and Institute between December 2018 and June 2023. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. Propensity score matching (PSM) and survival analysis were performed. Single-cell data of primary tumors (PTs) and MPE were obtained from GSE131907. This study performed cell subpopulation comparison, copy number variation (CNV) analysis of epithelial cells, differential gene expression analysis of malignant cells, gene set variation analysis (GSVA), single-cell regulatory network inference and clustering (SCENIC) analysis, and cell-cell interaction analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 116 patients with MPE and 279 patients without MPE were included in this study; after matching, each group included 112 patients. Patients with MPE had significantly shorter median PFS and OS compared to those without MPE (PFS: 8.0 &lt;i&gt;vs.&lt;/i&gt; 16.0 months, P&lt;0.001; OS: 20.0 months &lt;i&gt;vs.&lt;/i&gt; not reached, P&lt;0.001). Among MPE patients, intrapleural drug infusion did not significantly impact survival (PFS: 7.0 &lt;i&gt;vs.&lt;/i&gt; 11.0 months, P=0.09; OS: 20.0 &lt;i&gt;vs.&lt;/i&gt; 19.0 months, P=0.77). Genes such as &lt;i&gt;GTSF1&lt;/i&gt;, &lt;i&gt;MAGEA3&lt;/i&gt;, &lt;i&gt;XIST&lt;/i&gt;, and &lt;i&gt;FGB&lt;/i&gt; were significantly upregulated in malignant cells from MPE. In the MPE microenvironment, CD4⁺ T cells were the dominant T cell subset, naive B cells were selectively enriched, and monocytes/macrophages made up the majority of myeloid cells. The INTERFERON_ALPHA_RESPONSE pathway was enriched in diverse immune cell types from MPE, although this enrichment might not be statistically significant. Interferon regulatory factor 9 (IRF9) was widely upregulated in T cells, natural killer (NK) cells, B cells, and myeloid cells from MPE. Myeloid cells acted as the primary signal senders and receivers in the MPE microenvironment, while epithelial cells primarily functioned as signal senders.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Under immunochemotherapy, NSCLC patients with MPE still demonstrated poor prognosis. This provides an additional prognostic predictor for NSCLC patients receiving standard first-line treatment. However, intrapleural infusion of existing drugs did not improve survival in these patients. The high expressio","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3500-3519"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675772","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>Fusobacterium nucleatum</i> and IL-32 co-predict nodal metastasis preoperatively in head and neck cancer.","authors":"Zhenwei Wang, Huiying Huang, Xiaohui Yuan, Chiyao Hsueh, Ming Zhang","doi":"10.21037/tcr-2024-2539","DOIUrl":"10.21037/tcr-2024-2539","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with high rate of lymph node metastasis (LNM), which significantly impacts prognosis. This study aims to evaluate the potential utility of <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) and interleukin-32 (IL-32) as co-predictors for cervical LNM in HNSCC, enhancing preoperative assessment of metastatic status in patients.</p><p><strong>Methods: </strong>Clinical information, tissue, and plasma samples were collected from a cohort of 254 HNSCC patients. IL-32 expression was assessed using immunohistochemistry (IHC), while fluorescence in situ hybridization (FISH) was used to evaluate <i>F. nucleatum</i> enrichment in both tumor and paracancer tissue. Univariate and multivariate analyses identified significant risk factors.</p><p><strong>Results: </strong>IL-32 levels were higher in tumor tissue compared to paracancer tissue (P<0.001). Patients with high F. nucleatum enrichment had higher IL-32 expression (P=0.04). Through univariate and multivariate analyses, alcohol, Ki-67 (antigen Kiel-67) expression, <i>F. nucleatum</i> enrichment and IL-32 expression were identified as significant risk factors of LNM. The comparison of receiver operating characteristic (ROC) curves for these factors showed that the combined use of all chosen indicators resulted in the highest diagnostic accuracy.</p><p><strong>Conclusions: </strong>The enrichment of F. nucleatum in cancer tissue is positively correlated with high expression of IL-32, suggesting that these two novel indicators, <i>F. nucleatum</i> and IL-32, along with Ki-67 and alcohol, may serve as preoperative predictors for LNM in HNSCC. This discovery holds great potential to facilitate the development of more precise and personalized surgical strategies for patients.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3359-3372"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675729","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":"FBXO32 promotes gastric cancer progression by regulating NME1.","authors":"Xiong-Hui Rao, Huaiyu Qiu, Weifei Zhang, Nuoqing Weng, Xiaobin Wu","doi":"10.21037/tcr-2024-2426","DOIUrl":"10.21037/tcr-2024-2426","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer, a common cancer, has a high incidence rate, the 5-year survival rate of gastric cancer with distant metastasis is less than 10%, so finding new targets for gastric cancer is of clinical importance. As a member of the F-box protein family, F-box protein 32 (FBXO32) plays a role in various cancers, but its role in gastric cancer is currently unclear, this study mainly focused on the role and mechanism of FBXO32 in gastric cancer.</p><p><strong>Methods: </strong>The FBXO32 expression was found through The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. The FBXO32 expression in cell lines was found through Western blot assay. Cell cloning assay and Cell Counting Kit-8 (CCK8) assay were used to investigate the effect of FBXO32 on gastric cancer cell proliferation. Wound-healing assay and transwell assay were used to research the effect of FBXO32 on gastric cancer cell metastasis. Cancer stem cell sphere-forming assay was used to find out the effect of FBXO32 on the stemness of gastric cancer cells. Nude mouse tumorigenesis assay was used to investigate the effect of FBXO32 on gastric cancer tumor growth.</p><p><strong>Results: </strong>It was found that FBXO32 expression is elevated in gastric cancer, which is associated with poor prognosis. In addition, FBXO32 expression is also elevated in gastric cancer cell lines. The knockdown of FBXO32 can inhibit the proliferation, migration, invasion and stemness of gastric cancer cells, inhibit the subcutaneous tumor formation of gastric cancer cells in nude mice, and increase the expression of non-metastatic cells 1 (NME1). Low expression of NME1 is associated with poor prognosis in gastric cancer. The knockdown of NME1 expression can offset part of the tumor suppressor activity of the knockdown of FBXO32.</p><p><strong>Conclusions: </strong>It is believed that FBXO32 promotes the progression of gastric cancer by regulating NME1. Most importantly, our findings could provide information for the mechanism of gastric cancer and the discovery of new targets.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3520-3531"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675754","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":"Determining the optimal surgical margin using whole scene pathology and molecular surgical margin analysis in colorectal cancer radical surgery-a cross-sectional study.","authors":"Shuhan Lin, Hao Lai, Yazhen Zhu, Xianwei Mo, Yan Feng, Yuan Lin","doi":"10.21037/tcr-24-1146","DOIUrl":"10.21037/tcr-24-1146","url":null,"abstract":"<p><strong>Background: </strong>An inadequate surgical margin is the major reason for disease recurrence; however, tumor recurrence sometimes even occurs in patients with pathologically negative surgical margins. The aim of this study is to determine the ideal surgical margin in radical colorectal cancer (CRC) surgery using panoramic pathology coupled with a molecular surgical margin (MSM) analysis.</p><p><strong>Methods: </strong>The surgical specimens and clinical data of 194 CRC patients at the Guangxi Medical University Cancer Hospital from January 2016 to December 2019 were collected. Specifically, whole pathological sections of intact primary lesions of CRC were collected. Carcinoembryonic antigen (CEA) and methylation detection were used to analyze the molecular changes and protein expression patterns of different regions.</p><p><strong>Results: </strong>A total of 194 patients with high-quality sections and complete clinical data were included in this study. Different tumor cells and different regions of the primary focus of CRC had different protein expression patterns, and some cells expressed multiple proteins. The submucosal interstitial space of the tumor margin (i.e., the extension area) and the submucosal space near the cancer area was obvious. The positive rate of CEA in the normal mucosal tissues of distant cancer was 19.15%.</p><p><strong>Conclusions: </strong>A tumor is a disease caused by molecular regulation failure and internal environment disorder at the high molecular level of the body. \"Cell-cell\" interactions may play an important role. In tumor surgery, the cutting edge may not always need to be as extensive as possible, especially when function preservation is important, which affects the quality of life of patients and ultimately affects the actual treatment outcomes. Further high-powered randomized trials need to be conducted to confirm the results of this study.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3532-3541"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675716","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>ROS1</i> fusion-positive non-small cell lung cancer-repotrectinib as a new treatment option.","authors":"Sacha I Rothschild, Laetitia A Mauti","doi":"10.21037/tcr-2025-263","DOIUrl":"10.21037/tcr-2025-263","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3272-3276"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675730","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":"Blocking of CDC25B suppresses sarcoma progression via arresting cell cycle.","authors":"Renqin Lin, Jianhua Lin","doi":"10.21037/tcr-2024-2328","DOIUrl":"10.21037/tcr-2024-2328","url":null,"abstract":"<p><strong>Background: </strong>Soft tissue sarcoma is a malignant tumor originating from mesenchymal tissue, accounting for approximately 1% of adult malignancies. Cell division cycle protein 25B (CDC25B) plays a crucial role in human diseases, however, its function in soft tissue sarcoma remains poorly understood. This study aims to explore the prognostic and therapeutic values of CDC25B in sarcoma.</p><p><strong>Methods: </strong>The expression and prognostic values of CDC25B in sarcoma were analyzed using bioinformatics approaches. Additionally, a CDC25B inhibitor (CDC25B-IN-1) was used to evaluate the potential therapeutic value of the CDC25B target using Cell Counting Kit-8 (CCK-8), quantitative polymerase chain reaction (qPCR) detection, 5-ethynyl-2'-deoxyuridine (EdU), colony formation, transwell, wound healing, flow cytometry and western blot (WB) assays.</p><p><strong>Results: </strong>The bioinformatics analysis found that CDC25B is overexpressed in sarcoma tissues, and high expression of CDC25B correlated with lower disease-specific survival (DSS), progress-free interval (PFI), and overall survival (OS). The univariate and multivariate analysis identified CDC25B as an independent prognostic biomarker in sarcoma. Experimental validation demonstrated that blocking CDC25B using CDC25B inhibitor (CDC25B-IN-1) can suppress sarcoma progression by inducing G2 cell cycle arrest.</p><p><strong>Conclusions: </strong>CDC25B is highly expressed in sarcoma, and blocking of CDC25B can suppress sarcoma progression by inducing G2 cell cycle arrest. These findings suggest that CDC25B may serve as a potential molecular biomarker and therapeutic target for sarcoma.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3438-3451"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675734","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":"Carfilzomib plus pomalidomide and dexamethasone as salvage therapy in patients with relapsed or refractory multiple myeloma in China: a retrospective study.","authors":"Xibin Xiao, Yanping Shao, Xian Li, Huawei Jiang, Wei Jiang, Panpan Chen, Jing Xie, Wenbin Qian","doi":"10.21037/tcr-2024-2688","DOIUrl":"10.21037/tcr-2024-2688","url":null,"abstract":"<p><strong>Background: </strong>Regimens based on carfilzomib have shown significant improvement in survival for relapsed or refractory multiple myeloma (RRMM), but the combination of carfilzomib, pomalidomide and dexamethasone (KPd) has been scarcely investigated in China. This study aimed to evaluate the efficacy and safety of KPd regimen in Chinese patients with RRMM.</p><p><strong>Methods: </strong>Thirty-eight patients who had experienced one or more lines of therapy followed by the KPd regimen were retrospectively enrolled. After 4 cycles, the investigator switched eligible patients to maintenance therapy. The primary outcome was the objective response rate (ORR). The secondary endpoints included progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were also observed.</p><p><strong>Results: </strong>After 4 cycles of the KPd regimen, 23.7% of patients (9/38) achieved a complete response (CR), 42.1% (16/38) for very good partial response (VGPR), and 21.1% (8/38) for partial response (PR). The ORR was 86.8%. Of 33 patients who underwent maintenance therapy, 21 were administered the KPd regimen and 6 received daratumumab. The median PFS was 13.4 months and the median OS was not reached. Each patient experienced at least 2 AEs, mainly, neutropenia and anemia. Only 3 patients experienced Grade 3 AEs, and none of the other AEs was higher than Grade 2. No patient reported having experienced Grades 4-5 AEs.</p><p><strong>Conclusions: </strong>The KPd regimen showed encouraging activity and manageable toxicity for RRMM patients in China.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3351-3358"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675735","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 <i>MBD3/UHRF1</i> methylation-regulator-based prognostic model for pancreatic cancer survival.","authors":"Xue Cheng, Yangmei Zhang, Chunbin Wang, Kai Chen","doi":"10.21037/tcr-24-1887","DOIUrl":"10.21037/tcr-24-1887","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation plays a crucial role in the onset and progression of cancer. However, the complex technology and high costs required for methylation detection limit its clinical application. DNA methylation regulators are essential for maintaining the precision and stability of gene methylation, and their aberrant expression can lead to abnormal methylation levels. Whereas the role of combinatorial methylation regulators in pancreatic cancer (PCA) risk remains unclear, we developed a model using 20 DNA methylation regulators to predict patient prognosis and assess treatment response.</p><p><strong>Methods: </strong>Gene expression and clinical data from 331 PCA patients [The Cancer Genome Atlas (TCGA)-PCA, n=177; Gene Expression Omnibus (GEO)-PCA, n=154] were analyzed. TCGA data were used as the training set, and GEO data were used as the validation set. Inclusion criteria were complete survival data. Univariate and least absolute shrinkage and selection operator (LASSO)-Cox regression identified prognostic DNA methylation regulators. The model's predictive accuracy was validated using time-dependent receiver operating characteristic (ROC) curves. Differences in immune cell infiltration and drug sensitivity were also assessed.</p><p><strong>Results: </strong>A total of 331 PCA patients were analyzed, with a median overall survival (OS) of 1.2 and 1.4 years, respectively. Univariate Cox regression identified seven DNA methylation regulators (<i>DNMT3A</i>, <i>TET3</i>, <i>MBD3</i>, <i>MBD2</i>, <i>ZBTB38</i>, <i>UHRF1</i>, <i>UNG</i>) associated with prognosis, of which <i>MBD3</i> and <i>UHRF1</i> were selected via LASSO-Cox regression to construct the final model. The model demonstrated robust prognostic performance, with low-risk patients in both cohorts showing significantly longer OS compared to high-risk groups (P<0.001). ROC analysis confirmed reliability, yielding area under the curve (AUC) values of 0.662 (1-year), 0.684 (2-year) and 0.673 (3-year) in TCGA, and 0.629 (1-year), 0.663 (2-year) and 0.624 (3-year) in GEO. Drug sensitivity analysis further revealed that the low-risk group exhibited enhanced responses to epirubicin (P<0.001), irinotecan (P<0.001), and Poly(ADP-ribose) polymerase (PARP) inhibitors (niraparib P<0.001, olaparib P<0.001), suggesting potential therapeutic implications.</p><p><strong>Conclusions: </strong>Our findings suggest that the prognostic model, which is based on <i>MBD3</i> and <i>UHRF1</i> expression, may improve prognostic stratification in PCA patients and assess drug efficacy. This model represents a step toward epigenetic-based oncology, though its impact on treatment decisions remains to be validated.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3542-3553"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675745","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":"Polyamine metabolism and immune related genes as prognostic features in breast cancer: a novel risk model approach.","authors":"Weimiao Li, Changyou Shan, Liang Liang, Guoxu Zheng, Shuqun Zhang","doi":"10.21037/tcr-2024-2505","DOIUrl":"10.21037/tcr-2024-2505","url":null,"abstract":"<p><strong>Background: </strong>The biological role of polyamine metabolism-related genes (PMRGs) in breast cancer (BRCA) through immune mediation is not well understood. Consequently, this study aimed to explore the prognostic features connected to PMRGs and immune-related genes (IRGs) in BRCA via bioinformatics analysis.</p><p><strong>Methods: </strong>We analyzed The Cancer Genome Atlas (TCGA)-BRCA and GSE20685 datasets. Differential expression analysis revealed differentially expressed genes (DEGs) in TCGA-BRCA, which intersected with 1,793 IRGs and 59 PMRGs to identify candidate genes. A least absolute shrinkage and selection operator (LASSO) Cox regression model was used to screen prognostic genes, which were then used to develop a risk model. This model was validated in both datasets. A nomogram was constructed using independent prognostic factors from univariate and multivariate Cox regression analyses to predict BRCA patient survival. The immune microenvironment landscape and gene set enrichment analysis (GSEA) results were also characterized.</p><p><strong>Results: </strong>Among 9,558 DEGs, 1,793 IRGs, and 59 PMRGs, 10 candidate genes were identified, with <i>PSME2</i>, <i>PSMB8</i>, and <i>PSMD14</i> selected as prognostic genes. The risk model stratified BRCA patients into high- and low-risk groups, with high-risk patients showing worse survival according to Kaplan-Meier analysis. The nomogram, which is based on the pathological stage and risk score, accurately predicts patient viability. High-risk patients have poor immune responses. GSEA revealed immune-related pathway involvement. PSME2 and PSMB8 were upregulated in the control samples, whereas PSMD14 was increased in the BRCA samples. The CCK8 assay results indicated that PSMD14 significantly promotes the proliferation of BRCA cells.</p><p><strong>Conclusions: </strong>PMRGs and IRGs, specifically <i>PSME2</i>, <i>PSMB8</i>, and <i>PSMD14</i>, are potential prognostic markers in BRCA. A risk model and nomogram based on these genes were developed to assess BRCA prognosis effectively. These tools can improve the prognostic assessment of BRCA patients.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 6","pages":"3714-3729"},"PeriodicalIF":1.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675765","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}