Translational cancer research最新文献

{"title":"Integrated machine learning constructed a circadian-rhythm-related model to assess clinical outcomes and therapeutic advantages in hepatocellular carcinoma.","authors":"Ziyuan Xu, Wei Huang, Xi Zou, Shenlin Liu","doi":"10.21037/tcr-24-1155","DOIUrl":"https://doi.org/10.21037/tcr-24-1155","url":null,"abstract":"<p><strong>Background: </strong>Circadian rhythm (CR) coordinates a variety of internal biological processes with the external daily cycles of light and dark. However, the implications of CR-related regulator in hepatocellular carcinoma (HCC) are quite obscure. Here, we aimed to identify pivotal CR-related markers in HCC for predicting survival and treatment outcomes.</p><p><strong>Methods: </strong>The prognostic value of CR regulators in HCC was analyzed. Multi-step machine learning feature selection approaches were employed to establish a model. Thereafter, we evaluated its capacity of clinical prediction and treatment guidance.</p><p><strong>Results: </strong>First, we depicted the prognostic stratification value of CR regulators in HCC. Two CR-related phenotypes were identified, revealing a distinct clinical outcome, biological pathways and drug sensitivity. Subsequently, via four topological approaches and differentially expressed genes (DEGs) from real-world cohorts, we screened out CRY2 as the pivotal CR regulator with significant prognostic value in HCC. We performed the relevant basic assay validation for CRY2. Overexpression of CRY2 inhibited the proliferation and migration abilities of Huh7 and Hep3B cells. Moreover, three machine learning algorithms [random forest (RF), extreme gradient boosting (XGBoost) and least absolute shrinkage and selection operator (LASSO)] were implemented to construct a risk-scoring model named CR predictor, which exhibited clinical benefits and therapeutic advantages for HCC. An online nomogram based on CR predictor was developed for predicting individualized survival (https://lihc.shinyapps.io/CR_predictor/). Finally, Mendelian randomization (MR) was performed. Among model genes in CR predictor, PPARGC1A revealed a significant causal effect on HCC.</p><p><strong>Conclusions: </strong>We proposed a CR-related risk classifier in HCC, to predict patients' overall survival (OS) and therapeutic response. Targeting CR could be a promising treatment modality against HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1799-1823"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000422","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":"Enhanced prognostic prediction of cancer-specific mortality in elderly bladder cancer patients post-radical cystectomy: an XGBoost model study.","authors":"Gaowei Li, Kang Xia","doi":"10.21037/tcr-24-2023","DOIUrl":"https://doi.org/10.21037/tcr-24-2023","url":null,"abstract":"<p><strong>Background: </strong>Tumor stage, surgery and age are positively correlated with cancer-specific mortality (CSM) in patients diagnosed with bladder cancer (BCa). In light of the successful application of machine learning to process big data in many fields outside of medicine, we aimed to establish and validate whether machine learning models could improve our ability to predict the development of CSM in elderly BCa patients after radical cystectomy (RC).</p><p><strong>Methods: </strong>Data on eligible patients diagnosed with BCa were obtained from the Surveillance, Epidemiology, and End Results database (2000-2021) and divided into training and validation cohorts in a ratio of 7:3. First, risk factors for the development of CSM in patients were identified by Cox regression analysis. Then, iterative testing and tuning through automated hyperparameter optimization and ten-fold cross-validation were performed to generate stable extreme gradient boosting (XGBoost) models with optimal performance. Receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve and confusion matrix were used to evaluate the performance of XGBoost model.</p><p><strong>Results: </strong>There were 11,763 patients included, of which 5,788 died from BCa. By the comparison of different machine learning models, the final XGBoost model we constructed showed high accuracy and precision in predicting the development of CSM in BCa patients (6-month CSM: AUC =0.799, 12-month CSM: AUC =0.756, 36-month CSM: AUC =0.746, and 60-month CSM: AUC =0.745). The results of accuracy, precision, recall and F1 score confirmed the superior performance of the XGBoost model. The important scores for clinical characteristics and the Shapley Additive Explanations plots highlighted the importance of key factors: chemotherapy, tumor stage, marital status, and tumor size were the top four factors in all models.</p><p><strong>Conclusions: </strong>Our study validated and confirmed the feasibility and high performance of the XGBoost model in predicting CSM in elderly BCa patients after RC. The potential of machine learning contributes to accurately predict the prognosis of cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1902-1914"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Shenling Baizhu Powder on lipid profiles and body mass index in breast cancer patients under adjuvant chemotherapy: a retrospective study.","authors":"Jiaqing Song, Ying Jin, Qinghong Yu, Hongting Wu, Hailong Li, Geok Hoon Lim, Marcelo Antonini, Xiufei Gao","doi":"10.21037/tcr-2024-2658","DOIUrl":"https://doi.org/10.21037/tcr-2024-2658","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Breast cancer is the second most common cancer worldwide. Chemotherapy often causes dyslipidemia and obesity in breast cancer patients. Monitoring lipid profiles and body mass index (BMI) is crucial to evaluate chemotherapy's metabolic side effects, identify interventions to mitigate them, and understand health risks linked to weight changes during treatment. Shenling Baizhu Powder (SLBZP), a traditional Chinese medicine (TCM), treats spleen-stomach ailments by boosting spleen function, enhancing qi, and reducing dampness. SLBZP has potential benefits in managing chemotherapy-induced dyslipidemia and improving overall metabolic health in cancer patients. This study retrospectively examined the effects of SLBZP on blood lipid levels and BMI in breast cancer patients undergoing adjuvant chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study reviewed the medical records of patients who were diagnosed with breast cancer at the Breast Surgery Department of Zhejiang Provincial Hospital of Traditional Chinese Medicine from January 2022 to December 2023. Based on the inclusion criteria, a total of 180 eligible patients were included and divided into an observational group (which received SLBZP) and a control group (which did not receive SLBZP) during chemotherapy. Patients' clinical data, including age at diagnosis, menopausal status, tumor location, smoking and drinking habits, tumor molecular type, tumor node metastasis (TNM) stage, chemotherapy drugs, targeted therapy, lipid levels, and BMI before and after chemotherapy, were collected. Statistical analyses were conducted using SPSS 25.0.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After chemotherapy, the control group showed significant increases in total cholesterol (TC) (P=0.03), triglyceride (TG) (P=0.001), low-density lipoprotein cholesterol (LDL-C) (P=0.02), and apolipoprotein B (ApoB) (P=0.01) levels. In the observational group, the TC, TG, and LDL-C levels remained stable (P&gt;0.05), but the high-density lipoprotein cholesterol (HDL-C) (P=0.001) and apolipoprotein A1 (ApoA1) (P&lt;0.001) levels significantly decreased, and BMI (P=0.02) significantly increased. The subgroup analysis revealed that the taxane followed by anthracycline subgroup showed significant increases in BMI (P=0.007) and significant decreases in the HDL-C (P=0.007) and ApoA1 (P&lt;0.001) levels, while the taxane subgroup showed a significant decrease in the HDL-C level post-chemotherapy (P=0.003). In the control group, the TG (P=0.002) and LDL-C (P=0.02) levels were significantly elevated in the taxane followed by anthracycline subgroup post-chemotherapy. No significant changes were observed in BMI or the other lipid indexes in the remaining chemotherapy drug regime subgroups (P&gt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Chemotherapy increased the TC, TG, LDL-C, and ApoB levels in breast cancer patients, but SLBZP mitigated dyslipidemia. The patients who received SLBZP also showed increased BMI post-chemotherap","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1952-1970"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996361","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":"Circulating tumor cell-based PSMA and PSA expression as a predictive and prognostic tool in prostate cancer.","authors":"Panagiotis J Vlachostergios","doi":"10.21037/tcr-2024-2512","DOIUrl":"https://doi.org/10.21037/tcr-2024-2512","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1511-1515"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027880","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":"Small peritoneal macrophages are accelerators of peritoneal metastasis of colorectal cancer.","authors":"Wanli Yang, Feng Jiang, Lixia Xu, Nan Pang, Chao Yang, Ruihua Yu, Haiqun Chen","doi":"10.21037/tcr-24-1707","DOIUrl":"https://doi.org/10.21037/tcr-24-1707","url":null,"abstract":"<p><strong>Background: </strong>The peritoneal cavity (PerC) constitutes a distinct anatomical compartment that harbors various subpopulations of peritoneal macrophages. However, there remains a significant gap in our understanding of the functions of these macrophage subpopulations in the context of peritoneal metastasis of colorectal cancer (PM-CRC) and their roles in the tumor progression process. This investigation seeks to analyze the characteristics of large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), in the context of PM-CRC.</p><p><strong>Methods: </strong>A murine model of PM-CRC was developed through the intraperitoneal administration of the MC38 colorectal cancer cell line into C57BL/6 mice. Peritoneal effusions were subsequently collected at various time points post-injection and subjected to analysis via flow cytometry, cell co-culture assays, among other techniques. Additionally, clodronate liposomes were employed to deplete peritoneal macrophages in order to investigate the impact of SPMs on tumor progression and survival in the PM-CRC mouse model.</p><p><strong>Results: </strong>The findings of this study demonstrated a significant increase in the number of SPMs during the progression of PM-CRC, concomitant with a decrease in the proportion of LPMs. Notably, SPMs exhibited a macrophage phenotype conducive to tumor growth. In the PM-CRC mouse model, the dynamic escalation of SPMs following lipopolysaccharide stimulation was associated with a reduced survival rate. However, the depletion of SPMs using clodronate liposomes in the later stages of the model effectively extended the survival period in cases of PM-CRC.</p><p><strong>Conclusions: </strong>The findings of this study suggest that SPMs acts as a catalyst in the progression of peritoneal metastasis in colorectal cancer, thereby identifying it as a potential therapeutic target for managing this condition.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1626-1637"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999199","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":"KRT14 knockdown reduces cisplatin resistance by lowering LRP11 expression levels in cisplatin-resistant ovarian cancer cell lines.","authors":"Zequn Liu, Tingsong Weng, Mi Cheng, Tingying Lei, Du Xiao, Qiong Deng, Tianmei Wu","doi":"10.21037/tcr-24-1795","DOIUrl":"https://doi.org/10.21037/tcr-24-1795","url":null,"abstract":"<p><strong>Background: </strong>Platinum resistance is a major cause of mortality in patients with advanced ovarian cancer. Understanding the mechanisms underlying this resistance is essential for developing effective treatments to improve patient survival. Therefore, this study aimed to explore the role and mechanisms of keratin 14 (KRT14) in regulating cisplatin resistance in ovarian cancer.</p><p><strong>Methods: </strong>We utilized quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting to measure messenger RNA (mRNA) and protein expression levels, respectively. Cisplatin-resistant cell lines (SK-OV-3/DDP and A2780/DDP) were transfected with small interfering RNA (siRNA) targeting KRT14 (si-KRT14) or a plasmid containing low-density lipoprotein receptor-related protein 11 (LRP11) to knock down KRT14 or overexpress LRP11, respectively. Differentially expressed mRNAs were identified using Illumina RNA sequencing. Cell viability and half-maximal inhibitory concentration (IC₅₀) values were determined via cell counting kit-8 (CCK-8) assays, while apoptosis was assessed using flow cytometry and Hoechst 33258 staining.</p><p><strong>Results: </strong>KRT14 mRNA and protein levels were significantly higher in SK-OV-3/DDP and A2780/DDP cells compared with their parental counterparts. KRT14 knockdown reduced the IC₅₀ values, increased apoptosis, and decreased the levels of the multidrug resistance (MDR)-related proteins P-glycoprotein (P-gp) and MDR-associated protein 1 (MRP1). KRT14 knockdown in SK-OV-3/DDP and A2780/DDP cells revealed 24 differentially expressed mRNAs. Further analysis revealed that KRT14 knockdown notably reduced LRP11 expression. LRP11 overexpression increased IC₅₀ values, suppressed apoptosis, and enhanced MDR-related protein expression, thus counteracting the effects of KRT14 knockdown.</p><p><strong>Conclusions: </strong>Cisplatin-resistant ovarian cancer cell lines revealed elevated KRT14 expression. KRT14 knockdown reduced cisplatin resistance by lowering LRP11 expression. Therefore, KRT14 may play a crucial role in mediating cisplatin resistance in ovarian cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1786-1798"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000424","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":"Estrogen receptor β inhibits breast cancer migration and promotes its apoptosis through NF-κB/IL-8 signaling.","authors":"Yanke Sui, Zuge Liu, Yao Yao, Shuting Zhang, Yuxiang Wang, Yuanyuan Wang, Bin Kong","doi":"10.21037/tcr-24-1267","DOIUrl":"https://doi.org/10.21037/tcr-24-1267","url":null,"abstract":"<p><strong>Background: </strong>Estrogen receptor β (ERβ) has been confirmed to play a tumor suppressor effect in various cancers, but its role in breast cancer is still unclear, especially in triple-negative breast cancer. In this study, we aim to explore the expression of ERβ in breast cancer and its influence on the biological behavior of breast cancer cells, including its potential mechanisms of action.</p><p><strong>Methods: </strong>MCF-7 and MDA-MB-231 breast cancer cell lines were transfected with ERβ-overexpressing lentivirus and treated with pyrrolidinedithiocarbamate ammonium, a specific inhibitor of NF-κB. Cell Counting Kit-8, colony formation, and apoptosis assays were used to examine breast cancer cells viability <i>in vitro.</i> We further investigated breast cancer cells mobility and migration through wound healing and transwell assays. Western blot and quantitative real-time polymerase chain reaction analysis determined the expression of related genes at the protein and messenger RNA levels.</p><p><strong>Results: </strong>Breast cancer tissues displayed significantly lower ERβ messenger RNA and protein levels compared to adjacent healthy tissues. Conversely, interleukin-8 (IL-8) messenger RNA and protein levels were significantly higher in cancer tissues. ERβ overexpression led to a reduction in the expression of NF-κB pathway proteins like p-IκBα and p-P65, thereby inhibiting the pathway and consequently decreasing the expression of the inflammatory factor IL-8. This resulted in decreased mobility and migration of breast cancer cells, accompanied by increased apoptosis.</p><p><strong>Conclusions: </strong>This study demonstrates that ERβ suppresses the NF-κB/IL-8 signaling axis by inhibiting the phosphorylation of IκBα and P65, consequently restricting breast cancer cell mobility and migration while promoting apoptosis.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1824-1835"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000442","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":"Comparative survival analysis of stage T1-T2N0M0 lung squamous cell carcinoma and adenocarcinoma using SEER data, and nomogram analysis for early-stage lung squamous cell carcinoma.","authors":"Chang Liu, Cheng Fang, Dan Shen","doi":"10.21037/tcr-24-1602","DOIUrl":"https://doi.org/10.21037/tcr-24-1602","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is one of the most common malignant tumors worldwide. It is of great significance to conduct in-depth research on early lung cancer with a better prognosis. This study aimed to use the Surveillance, Epidemiology, and End Results (SEER) database to compare the clinicopathological characteristics and survival between early squamous cell carcinoma (SQCC) and adenocarcinoma (AC) under the same treatment model, and develop a nomogram for early lung SQCC.</p><p><strong>Methods: </strong>This study examined 40,325 cases of stage T1-T2N0M0 lung SQCC and AC from 2004 to 2019. Propensity score matching (PSM) was used to reduce bias. Kaplan-Meier curves and Cox proportional hazards models were used for assessing lung cancer-specific survival (LCSS) and overall survival (OS) under various treatments. A nomogram for early-stage SQCC was constructed and validated using the concordance index (C-index), calibration curves, and decision curve analysis (DCA).</p><p><strong>Results: </strong>In patients with T1-T2N0M0 non-small cell lung cancer (NSCLC), when only radiotherapy was performed, the LCSS of patients in the SQCC group was worse than that of the AC group [hazard ratio (HR) =1.20, 95% confidence interval (CI): 1.079-1.336, P<0.001], and same for 3-year LCSS (55.9% <i>vs.</i> 62.7%) and the 5-year LCSS (43.6% <i>vs.</i> 47.8%). The OS of patients in the SQCC group was worse than the AC group (HR =1.32, 95% CI: 1.215-1.429, P<0.001). When only surgical treatment was performed, no statistically significant difference was found in the LCSS between the two groups (HR =1.03, 95% CI: 0.965-1.092, P=0.41). The OS of patients in the SQCC group was worse than the AC group (HR =1.25, 95% CI: 1.200-1.309, P<0.001). Additionally, a nomogram was created to predict survival rates for early-stage lung SQCC patients.</p><p><strong>Conclusions: </strong>The prognosis of patients with T1-T2N0M0 lung SQCC is worse than that of AC patients. Individualized treatment is recommended in the early stages.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1691-1709"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011770","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, prognostic factors and nomograms for distant metastasis in colorectal neuroendocrine neoplasms: a SEER-based study.","authors":"Yuqin Bai, Na Lei, Pan Zhang, Qian Yang, Fei Feng, Yue Zhao","doi":"10.21037/tcr-24-2018","DOIUrl":"https://doi.org/10.21037/tcr-24-2018","url":null,"abstract":"<p><strong>Background: </strong>Distant metastasis is uncommon in colorectal neuroendocrine neoplasms (CRNENs). However, the prognosis of patients with distant metastasis is often poor, so it is crucial to detect distant metastasis in time. This article aims to study the risk factors and prognostic factors for the development of distant metastasis in patients with CRNENs and to construct two related nomograms.</p><p><strong>Methods: </strong>Patient data were obtained through the Surveillance, Epidemiology, and End Results (SEER) database, and the inclusion population was identified according to inclusion and exclusion criteria. Logistic regression analysis was used to determine risk factors for distant metastasis in patients with CRNENs. Cox regression analysis was utilized to identify prognostic factors in patients with CRNENs with distant metastasis. Two nomograms were created and the predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, the calibration curve, and decision curve analysis (DCA) curves.</p><p><strong>Results: </strong>We included 9,142 patients with CRNENs and 859 patients with distant metastasis. Age, race, marital status, primary site, histological grade, T stage, N stage, and tumor size were independent risk factors. Age, primary site, histological grade, N stage, tumor size, dissected lymph nodes, and surgery were independent prognostic factors. The constructed nomogram can predict the occurrence and prognosis of distant metastasis in patients with CRNENs.</p><p><strong>Conclusions: </strong>The nomogram developed in this paper may contribute to the diagnosis and prognosis of distant metastasis in patients with CRNENs and may help clinicians make better clinical decisions.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1576-1595"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of mitochondrial DNA methylation-related prognostic biomarkers in hepatocellular carcinoma using The Cancer Genome Atlas (TCGA) database.","authors":"Shanfan Shi, Wen Liang, Yunxue Qie, Runtong Wu, Yejin Zhu","doi":"10.21037/tcr-2025-546","DOIUrl":"https://doi.org/10.21037/tcr-2025-546","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with complex pathogenesis and limited therapeutic options. Emerging evidence suggests that mitochondrial DNA methylation (MTDM) plays a regulatory role in tumorigenesis, but its specific contributions to HCC progression, prognosis, and tumor microenvironment (TME) remodeling remain poorly characterized. This study aims to investigate MTDM-associated molecular subtypes in HCC, screen potential prognostic biomarkers linked to MTDM dysregulation, and explore their implications for immune landscape heterogeneity and therapeutic response.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Several HCC datasets and MTDM-related prognostic genes associated with the clinicopathological features of HCC were collected from public databases. The ConsensusClusterPlus tool was used for unsupervised clustering to identify the MTDM differentially expressed genes (DEGs) and then the candidate genes. Subsequently, a univariate Cox regression analysis, least absolute shrinkage and selection operator regression analysis, and multivariate Cox regression analysis were performed on the data of the candidate genes to identify and validate the prognostic genes. Additionally, differences in the TME and the enriched pathways between the high- and low-risk groups were evaluated, and drug response prediction was performed using the pRRophetic R package.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Eight MTDM-related genes were found to be differentially expressed in HCC. In relation to these MTDM-related DEGs, two molecular subtypes of HCC (Cluster 1 and Cluster 2) were identified. In addition, 333 candidate genes were identified. The regression analysis of the DEGs included in the risk model identified &lt;i&gt;ADH4&lt;/i&gt; and &lt;i&gt;DNASE1L3&lt;/i&gt; as prognostic genes that could be used to predict the overall survival of the HCC patients. The results of the differential immune recognition by immune cells using immune cell infiltration and the prognostic genes showed that the strongest negative correlation [correlation coefficient (r) =-0.312] was between &lt;i&gt;ADH4&lt;/i&gt; and activated cluster of differentiation (CD)4&lt;sup&gt;+&lt;/sup&gt; T cells, while the strongest positive correlation (r=0.332) was between &lt;i&gt;DNASE1L3&lt;/i&gt; and effector memory CD8&lt;sup&gt;+&lt;/sup&gt; T cells. The gene set enrichment analysis revealed five Kyoto Encyclopedia of Genes and Genomes pathways in the high- and low-risk groups that were clearly enriched in biological processes and signaling pathways, such as fatty acid degradation and peroxisome. The chemotherapeutic drug sensitivity analysis revealed significant differences in sensitivity to BI.2536 [a Polo-like kinase 1 (Plk1) inhibitor], A.443654 [a protein kinase B (Akt) 1/2 inhibitor], and ABT.888 [Veliparib, a poly(ADP-ribose) polymerase 1/2 (PARP1/2) inhibitor] between the high- and low-risk groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study constructed a risk model for HCC based on two ","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"2095-2112"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015412","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}