Translational cancer research最新文献

{"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":"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":"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":"Scoparone suppresses proliferation and cell cycle of hepatocellular carcinoma cells via inhibiting AKT/GSK-3β/cyclin D1 signaling pathway.","authors":"Mei Hong, Hao Zhu, Weikang Liu, Pengyu Zhang, Song Yu, Quangen Gao, Genhai Shen, Bin Li, Gang Wang","doi":"10.21037/tcr-24-1771","DOIUrl":"https://doi.org/10.21037/tcr-24-1771","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent cancer and the fourth leading cause of cancer-related mortality globally. Scoparone, a natural coumarin derivative primarily derived from Artemisia Capillaris Thunb, has demonstrated antitumor properties across various cancer types. However, its functions in HCC have not been clearly elucidated. This study aimed to investigate the antitumor effects of scoparone on the MHCC-97L and HCCC-9810 HCC cell lines.</p><p><strong>Methods: </strong>Cell proliferation was assessed through viability and colony formation assays. Migration and invasion capabilities of the cells were evaluated by wound healing assays and Transwell assays. Additionally, transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to uncover pathways linked to gene enrichment in the artemisinin treatment group. Western blotting and flow cytometry were utilized to analyze the expression of mechanistic proteins associated with artemisinin treatment in HCC.</p><p><strong>Results: </strong>Our findings revealed that scoparone effectively inhibited the proliferation, migration, and invasion of HCC cells. The genes affected by scoparone treatment were predominantly enriched in pathways related to the cell cycle. Specifically, scoparone reduced the expression of genes such as <i>CDK2, CDK3, CDK4, CDC25A, CCND1</i>, and <i>CCNE1</i>, while it increased the expression of <i>CDKN1A</i> (<i>p21</i>). Furthermore, scoparone suppressed the levels of cell cycle-related proteins CDK2, CDK4, and cyclin D1, along with the signaling pathways involving p-AKT and p-GSK-3β. Notably, the inhibitory effects of scoparone on HCC cell proliferation were partially reversed by the AKT activator, SC79.</p><p><strong>Conclusions: </strong>Scoparone inhibited HCC cell viability by targeting the AKT/GSK-3β/cyclin D1 pathway.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1638-1650"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045052","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":"Radiomics-clinical nomogram for preoperative tumor-node-metastasis staging prediction in breast cancer patients using dynamic enhanced magnetic resonance imaging.","authors":"Zhe Yang, Shouen Wang, Wei Yin, Ying Wang, Fanghua Liu, Jianshu Xu, Long Han, Chenglong Liu","doi":"10.21037/tcr-24-1559","DOIUrl":"https://doi.org/10.21037/tcr-24-1559","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is one of the most commonly diagnosed malignancies in women worldwide, and the disease burden continues to aggravate. The tumor-node-metastasis (TNM) staging information is crucial for oncology physicians to develop appropriate clinical strategies. This study aimed to investigate the value of a radiomics-clinical model for predicting TNM stage in breast cancer patients using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).</p><p><strong>Methods: </strong>DCE-MRI images from 166 patients with pathologically confirmed breast cancer were retrospectively collected, including early stage (TNM0-TNM2) and locally advanced or advanced stage (TNM3-TNM4). Included patients were divided into a training cohort (n=116) and a test cohort (n=50). The radiomics, clinical and integrated models were constructed and a nomogram was established to distinguish the TNM0-TNM2 stage from the TNM3-TNM4 stage. Receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) were employed to assess the predictability of the models.</p><p><strong>Results: </strong>Eighty-five patients were at the early stages, while 81 patients were at the other stages. In the training and test cohorts, the area under the curve (AUC) values for distinguishing early and advanced breast cancer were 0.870 and 0.818 for the nomogram, respectively. The nomogram calibration curves showed good agreement between the predicted and observed TNM stages in the training and test cohorts. The Hosmer-Lemeshow test showed that the nomogram fit perfectly in the two cohorts. DCA indicated that the nomogram displayed clear superiority in forecasting TNM staging over clinical and radiomic signatures.</p><p><strong>Conclusions: </strong>Compared to traditional imaging methods, the clinical-radiomics nomogram acquired by DCE-MRI could potentially be utilized to preoperatively evaluate the TNM stage of breast cancer with relatively high accuracy. It can be an effective method to guide clinical decisions.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1836-1848"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049663","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":"Triage of women with positive HPV: comparing DNA ploidy analysis with HPV 16/18 genotyping and cervical cytology.","authors":"Wei Song, Lan Zhu, Min Zheng, Hua Liu","doi":"10.21037/tcr-24-1455","DOIUrl":"https://doi.org/10.21037/tcr-24-1455","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer screening primarily uses the human papillomavirus (HPV) test with partial genotyping (HPV 16/18) and liquid-based cytology using ThinPrep cytology test (TCT) to triage women with a positive HPV test. Although quantitative DNA ploidy analysis has shown reliability, its integration into screening guidelines as a triage test, compared to partial genotyping and TCT, has not been fully established. The objective of the study is to evaluate the clinical utility of DNA ploidy analysis as a triage test for women with a positive HPV test in primary screening, comparing it to HPV 16/18 genotyping and TCT.</p><p><strong>Methods: </strong>We retrospectively analyzed data from 335 women aged ≥18 years who participated in a cervical cancer screening program at Shanghai Ruijin Hospital and underwent triage using HPV 16/18, TCT, and DNA ploidy testing. The sensitivities and specificities of these methods, both individually and combined, were evaluated.</p><p><strong>Results: </strong>The test showed sensitivities and specificities of 35.4% and 76.1% for HPV 16/18, 29.2% and 88.2% for TCT, and 93.8% and 92.7% for DNA ploidy, respectively. Combining these tests improved outcomes, with DNA ploidy plus HPV 16/18 genotyping showing enhanced sensitivity and high specificity. Notably, DNA ploidy alone identified high-grade squamous intraepithelial lesions (HSIL) and cervical cancer with a higher detection rate and lower positivity rate in triage than HPV 16/18 and TCT.</p><p><strong>Conclusions: </strong>DNA ploidy analysis demonstrated superior specificity and sensitivity in the triage of women with positive HPV test results, offering a more effective alternative for detecting high-grade lesions and cervical cancer. These findings support the potential of integrating DNA ploidy into current cervical cancer screening protocols to enhance triage effectiveness and reduce unnecessary colposcopy referrals.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 3","pages":"1664-1674"},"PeriodicalIF":1.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042801","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}