Translational cancer research最新文献

{"title":"A diagnostic test of two-dimensional ultrasonic feature extraction based on artificial intelligence combined with blood flow Adler classification and contrast-enhanced ultrasound for predicting <i>HER-2</i>-positive breast cancer.","authors":"Kun Wang, Xi Yang, Shuo Yang, Xian Du, Ruijing Shi, Wendong Bai, Yu Wang","doi":"10.21037/tcr-24-2182","DOIUrl":"10.21037/tcr-24-2182","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Human epidermal growth factor receptor 2 (&lt;i&gt;HER-2&lt;/i&gt;) was an important driver gene for breast cancer which had high degree of malignancy and poor prognosis. Ultrasonography was an important imaging method for the diagnosis of breast cancer, but its diagnostic efficacy of &lt;i&gt;HER-2&lt;/i&gt;-positive breast cancer was not satisfactory. To assess the predictive value of two-dimensional ultrasonic feature extraction based on artificial intelligence (AI) combined with blood flow Adler classification and contrast-enhanced ultrasound (CEUS) for &lt;i&gt;HER-2&lt;/i&gt;-positive breast cancer, we compared the value of the area under the receiver operating characteristic (ROC) curve (AUC) of the combined diagnosis model and single-factor models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective analysis was performed on 140 patients (88 &lt;i&gt;HER-2&lt;/i&gt;-positive and 52 &lt;i&gt;HER-2&lt;/i&gt;-negative). These patients were divided into internal test samples and external validation samples in a ratio of 7:3 randomly. The two samples were divided into &lt;i&gt;HER-2&lt;/i&gt;-positive group and &lt;i&gt;HER-2&lt;/i&gt;-negative group. All the patients were examined by two-dimensional ultrasound, color Doppler ultrasound, and CEUS, and AI was used to extract two-dimensional ultrasonic image features. Features of two-dimensional ultrasound included not parallel to the skin, irregular shape, unclear boundary, posterior echo attenuated, solid or cystic-solid mixed, microcalcification or coarse calcification were treated as &lt;i&gt;HER-2&lt;/i&gt;-positive. Levels of Doppler ultrasound included level 3 and level 4 were treated as &lt;i&gt;HER-2&lt;/i&gt;-positive. Features of CEUS included high enhancement, fast forward, centrifugal or diffuse, uneven, lesion range increased after CEUS, with perforating branches, unclear nodule boundary after CEUS were treated as &lt;i&gt;HER-2&lt;/i&gt;-positive. The ultrasonography characteristics in different ultrasonography methods were analyzed, the parameters with statistically significant differences between groups of internal test samples were incorporated to establish a joint diagnosis model. The sensitivity, specificity and accuracy of the combined diagnosis model and single-factor models were calculated, the ROC curve was drawn to evaluate the diagnostic efficacy of the combined diagnosis model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Long diameter direction, Adler grade of blood flow, contrast agent distribution characteristics, and nodule boundary after CEUS were statistically significant different between the positive and negative groups in internal test and external validation samples (P&lt;0.05). The sensitivity, specificity, accuracy of the combined diagnosis model were significantly higher than single-parameter diagnosis method both in internal test and external validation samples, and the kappa values of combined diagnosis model were highest. The AUC of the combined diagnosis model of internal test and external validation samples was 0.861 and 0.969, which was significantly highe","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"640-650"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459438","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 predictive nomogram for predicting liver metastasis in early-onset colon cancer: a population-based study.","authors":"Weichao Zeng, Yafeng Sun, Zhengrong Liao, Jianhua Xu","doi":"10.21037/tcr-24-1159","DOIUrl":"10.21037/tcr-24-1159","url":null,"abstract":"<p><strong>Background: </strong>The risk of liver metastasis (LM) may be estimated using predictive nomograms. While the nomogram has recently been applied in oncology, there are relatively few studies concentrating on predicting LM in patients with early-onset colon cancer. We aimed to identify independent risk factors for LM in patients with early-onset colon cancer and develop a nomogram for predicting the probability of LM in these patients.</p><p><strong>Methods: </strong>Our study encompassed 4,890 early-onset colon cancer patients with LM who were registered in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. These patients were randomly allocated into training and validation cohorts at a ratio of 7:3. Univariate and multivariate logistic regression analyses were conducted to identify the independent risk factors for LM, and a nomogram was developed using these factors. The model's discriminatory power, accuracy, and clinical utility were evaluated using receiver operating characteristics (ROC), calibration, and decision curve analyses.</p><p><strong>Results: </strong>Overall, 4,890 patients with early-onset colon cancer and LM were selected from the SEER database. LM incidence in these patients was 18.4%. Univariate and multivariate analyses revealed histological type, T stage, N stage, and carcinoembryonic antigen (CEA) level as independent risk factors. ROC curve analysis revealed that the predictive nomogram for LM risk had an area under the curve of 0.812 [95% confidence interval (CI): 0.795-0.829] and 0.809 (95% CI: 0.784-0.834) in the training and validation sets, respectively, demonstrating good discriminatory ability of the model. Calibration curve analysis showed good agreement between predicted values from the nomogram and actual observations, and the decision curve analysis (DCA) demonstrated the high clinical utility of the nomogram.</p><p><strong>Conclusions: </strong>LM incidence was higher in patients with early-onset colon cancer. Our nomogram demonstrates a high level of efficacy in predicting the risk of LM in patients with early-onset colon cancer, thereby assisting clinicians in making well-informed treatment decisions prior to further intervention.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"545-553"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459459","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":"Single-cell programmed cell death regulator patterns guide intercellular communication of cancer-associated fibroblasts that contribute to colorectal cancer progression.","authors":"Kai Yao, Shuo Zhang, Bo Zhu, Yun Sun, Ke Tian, Yan Yan, Yongquan Hu, Li Ren, Congli Zhang","doi":"10.21037/tcr-24-1301","DOIUrl":"10.21037/tcr-24-1301","url":null,"abstract":"<p><strong>Background: </strong>The significance of programmed cell death (PCD) in the context of cancer development and progression is widely acknowledged, yet its specific impact on cancer-associated fibroblasts (CAFs) remains a topic of ongoing investigation. Therefore, the study aims to explore the role of PCD in regulating CAFs and its potential implications for CRC progression.</p><p><strong>Methods: </strong>CAFs from single-cell data of 23 colorectal cancer (CRC) patients were clustered by non-negative matrix factorization (NMF) and the impact of these subpopulations on the prognosis of CRC patients was predicted using public database cohorts.</p><p><strong>Results: </strong>In total, we screened eight PCDs that are associated with significant prognostic impacts for CRC patients, and based on PCD regulators, we defined multiple subpopulations of CAFs associated with PCDs. Additionally, we found that the PCD key regulators may be closely related to the clinical and biological characteristics of CRC and the pseudotime trajectory of major CAFs subpopulations. Bulk RNA sequencing analyses revealed that subpopulations of CAFs mediated by PCD hold prognostic value for CRC patients. CellChat analysis further illustrated the extensive interactions between PCD-associated CAFs subpopulations and tumor epithelial cells. Following Cox regression and survival analyses, it was determined that the paraptosis-mediated CAFs subpopulation had the most pronounced impact on CRC patient prognosis, with DDIT3 identified as a marker protein influencing patient outcomes.</p><p><strong>Conclusions: </strong>Our study reveals for the first time how PCD-mediated communication between CAFs regulates tumor growth in CRC patients and influences their prognosis, and has identified that DDIT3⁺ CAFs associated with paraptosis exhibit the most pronounced influence on the prognosis of individuals with CRC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"434-460"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459558","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>EPB41L4A-AS1</i> regulates cervical cancer by proliferative cells: mendelian randomization and single-cell transcriptomics analyses.","authors":"Yifan Wang, Jia Yao, Meilian Wei, Qianru Jiang, Haiming Luo, Sidan Lai, Zhulin Liu, Hongsheng Zou, Chenlong Wang, Meijian Liao","doi":"10.21037/tcr-24-949","DOIUrl":"10.21037/tcr-24-949","url":null,"abstract":"<p><strong>Background: </strong>The current literature lacks reports on the roles of proliferative cells in tumorigenesis and causal relationship between proliferative cells and cervical cancer. This study aims to investigate the role and mechanism of proliferative cells in cervical cancer.</p><p><strong>Methods: </strong>Single-cell transcriptomics of cervical cancer were utilized to identify proliferative cells. Mendelian randomization (MR) and meta-analysis were employed to study the causal relationship between proliferative cells and cervical cancer. Additional assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, gene set enrichment analysis (GSEA), and weighted gene co-expression network analysis (WGCNA) were exploited to study function of <i>EPB41L4A-AS1</i> in the regulation of cell proliferation. Both complementary DNA (cDNA) microarray and GSEA were performed to elucidate the underlying mechanisms by which <i>EPB41L4A-AS1</i> influenced proliferative cells.</p><p><strong>Results: </strong>Cervical cancer exhibited a higher proportion of proliferative cells in tumor tissue compared to healthy tissue, as evidenced by single-cell transcriptomics. Genes specifically expressed in proliferative cells were found to be predictive of the prognosis of cervical cancer patients [P=0.009; hazard ratio (high groups) =1.893; 95% confidence interval: 1.169-3.064]. Proliferative cells, rather than squamous or columnar epithelial cells, were causally associated with cervical cancer. Mechanistically, <i>EPB41L4A-AS1</i> was found to regulate proliferative cells (P<0.005), described as <i>EPB41L4A-AS1</i>-regulated genes which were predominantly enriched in proliferative cells. The mapping of pathways associated with <i>EPB41L4A-AS1</i>-regulated genes to proliferative cells revealed a significant enrichment of mitosis-related pathways (normalized enrichment score >1). Furthermore, knockdown of <i>EPB41L4A-AS1</i> resulted in an increased number of cells during the M phase (Sh-NC: 2N: 74.5%, S: 11.7%, 4N: 10.0%; Sh-<i>EPB41L4A-AS1</i>: 2N: 66.0%, S: 11.2%, 4N: 18.7%), thereby promoting cell proliferation.</p><p><strong>Conclusions: </strong>This study offered a novel perspective on the role of <i>EPB41L4A-AS1</i> in regulating cervical cancer through its impact on proliferative cells.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"354-370"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459432","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":"Optimizing immunotherapy for lung cancer: integrating genetic alterations and the tumor mutational burden to refine patient selection.","authors":"Takahiro Sugawara, Taiki Hakozaki, Masahiro Seike, Yukio Hosomi","doi":"10.21037/tcr-24-1734","DOIUrl":"10.21037/tcr-24-1734","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"29-32"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459441","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":"Exploration of key pathogenic mechanisms and potential intervention targets of the traditional Chinese medicine Coptis chinensis in the treatment of cervical cancer based on network pharmacology and molecular docking techniques.","authors":"Ying Hou, Lei Zhang, Hequn Li, Renmin Zhang, Jiaxing Sun, Hui Jia, Hui Xu","doi":"10.21037/tcr-2024-2608","DOIUrl":"10.21037/tcr-2024-2608","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Traditional Chinese medicine (TCM) has shown potential in the treatment of cancer. This study investigated the molecular targets and mechanisms of Coptis chinensis in the treatment of cervical cancer using network pharmacology and bioinformatics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Effective Coptis chinensis components were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform based on the following criteria: drug-like properties (DLP) ≥0.18 and oral bioavailability (OB) ≥30%. Target genes were identified through DrugBank, while differentially expressed genes (DEGs) related to cervical cancer were sourced from the Gene Expression Omnibus (GEO) database (GSE7803) based on the following criteria: |log fold change| &gt;2 and P&lt;0.05. Common DEGs were identified through a Venn diagram analysis. The expression and prognostic relevance of the candidate genes were validated using The Cancer Genome Atlas (TCGA) database. Molecular docking was performed using Pubchem, Protein Data Bank (PDB), and CB-DOCK2. A gene set enrichment analysis (GSEA) was conducted to explore the potential mechanisms of DEGs. A retrospective analysis of cervical cancer patients (June 2021 to June 2022) was performed to examine the expression of key genes in the peripheral blood via enzyme-linked immunosorbent assay. A multivariate Cox regression was conducted to identify independent prognostic factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 10 effective Coptis chinensis compounds and 181 target genes were identified from the TCMSP database. The GEO analysis of GSE7803 identified 109 DEGs. The Venn diagram analysis identified the following seven shared DEGs: &lt;i&gt;AR, MAOB, CDKN2A, TOP2A, CXCL8&lt;/i&gt;, matrix metalloproteinase 1 (&lt;i&gt;MMP1&lt;/i&gt;), and &lt;i&gt;SPP1&lt;/i&gt;. &lt;i&gt;MMP1&lt;/i&gt; and &lt;i&gt;SPP1&lt;/i&gt; were confirmed to be upregulated candidate genes in cervical cancer tissues, and to be associated with a worse prognosis [overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI), P&lt;0.05]. Molecular docking showed that MMP1 had high binding affinity with quercetin (-9.2) while that of SPP1 was lower (-6.3). The GSEA indicated that MMP1 was involved in the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Janus kinase/signal transducer and activator of transcription (JAK/STAT), transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), and hypoxia-inducible factor 1 (HIF1) pathways, and apoptosis. The retrospective analysis demonstrated that &lt;i&gt;MMP1&lt;/i&gt; expression was significantly decreased in the peripheral blood of patients receiving conventional chemotherapy and Coptis chinensis compared to those receiving chemotherapy alone. Multivariate Cox regression confirmed that high &lt;i&gt;MMP1&lt;/i&gt; expression and a lack of Coptis chinensis treatment were independent risk factors for a poor prognosis (P&lt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;&lt;i&gt;MMP1&lt;/i&gt; could be a predictive biomarker for cervic","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"626-639"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458728","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":"Level and clinical significance of serum CXC chemokine ligand 13 in patients with hepatocellular carcinoma.","authors":"Ye-Ting Wu, Xiao-Juan Ran, Qi-Zhe Li, Yi-Qi Wu, Xiao-Xu Shen, Mao Mu, Quan Zhang","doi":"10.21037/tcr-24-1306","DOIUrl":"10.21037/tcr-24-1306","url":null,"abstract":"<p><strong>Background: </strong>CXC chemokine ligand 13 (CXCL13) serves as the ligand for chemokine receptor 5 (CXCR5), The CXCL13/CXCR5 signaling axis plays a crucial role in the pathogenesis and progression of various malignancies. This study aimed to assess the expression and role of serum CXCL13 in patients with hepatocellular carcinoma (HCC) and explore its clinical significance in the diagnosis, treatment, and prognosis evaluation of HCC.</p><p><strong>Methods: </strong>Serum samples and clinical data were collected from 74 HCC patients, 51 cirrhosis patients, and 53 healthy controls. The expression level of serum CXCL13 was measured using enzyme-linked immunosorbent assay (ELISA). Statistical software was employed to analyze the relationship between CXCL13 levels and clinicopathological features as well as laboratory indicators. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of CXCL13 and alpha-fetoprotein (AFP) for HCC.</p><p><strong>Results: </strong>The level of serum CXCL13 in the HCC group (275.96±145.35 pg/mL) was significantly higher than that in the cirrhosis group (172.11±142.78 pg/mL) and healthy control group (58.83±41.29 pg/mL). The level of CXCL13 in HCC patients with tumor node metastasis (TNM) stage III-IV was significantly higher than that in those with TNM stage I-II, as well as positively correlated with γ-glutamyltransferase (GGT) and model for end-stage liver disease (MELD) values. The area under the ROC curve for CXCL13, AFP, and the combination of CXCL13 with AFP were 0.819, 0.813, and 0.885 respectively. The sensitivity and specificity of the combined CXCL13 with AFP were 88.9% and 77.9% respectively. Moreover, the diagnostic efficacy of combining CXCL13 with AFP was significantly superior to that of using either CXCL13 or AFP alone.</p><p><strong>Conclusions: </strong>The expression of CXCL13 is upregulated in HCC patients and associated with tumor size, metastasis, GGT, and MELD score. Combining serum CXCL13 with AFP may hold clinical value to the diagnosis of HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"424-433"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459213","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":"METTL3 stabilizes SERPINE2 via the m6A modification to drive the malignant progression of gastric signet ring cell carcinoma.","authors":"Tan Yan, Qian Wang, Yuhui Liu","doi":"10.21037/tcr-24-896","DOIUrl":"10.21037/tcr-24-896","url":null,"abstract":"<p><strong>Background: </strong>Gastric signet ring cell carcinoma (GSRCC) is a highly lethal malignancy. Serpin family E member 2 (SERPINE2) is a pro-tumorigenic factor in cancer. Here, we sought to define the role of SERPINE2 in the pathogenesis of GSRCC.</p><p><strong>Methods: </strong>Messenger RNA (mRNA) expression was analyzed by quantitative polymerase chain reaction (PCR). Protein expression was tested by immunohistochemistry (IHC) and immunoblot assays. Proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) assay, and invasion and migration were detected by transwell assay. Tube formation assay was used to test the influence on angiogenesis. Cell apoptosis and M2 macrophage polarization were evaluated by flow cytometry. The methyltransferase-like 3 (METTL3)-SERPINE2 relationship was analyzed by RNA immunoprecipitation (RIP), luciferase, and mRNA stabilization assays. Xenograft experiments were used for assessment of METTL3's influence on tumorigenicity of GSRCC cells.</p><p><strong>Results: </strong>SERPINE2 and METTL3 levels were upregulated in human GSRCC. Functionally, SERPINE2 depletion enhanced apoptosis of GSRCC cells and diminished their proliferative, migratory and invasive capacities <i>in vitro</i>. Moreover, SERPINE2 depletion suppressed tube formation ability of human umbilical vein endothelial cells (HUVECs) and M2 polarization of THP-1-derived macrophages. Mechanistically, METTL3 induced SERPINE2 upregulation by enhancing <i>SERPINE2</i> mRNA stabilization. Our rescue experiments indicated that the effects of METTL3 depletion on cell phenotypes were due to the reduction of SERPINE2 expression. Additionally, METTL3 deficiency inhibited GSRCC xenograft growth <i>in vivo</i>.</p><p><strong>Conclusions: </strong>Our study defines the significant roles of the METTL3/SERPINE2 axis as an epigenetic mechanism in GSRCC progression. Our work may have diagnostic and/or therapeutic applications in GSRCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"78-92"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459377","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":"Deciphering the prognostic potential of a necroptosis-related gene signature in head and neck squamous cell carcinoma: a bioinformatic analysis.","authors":"Shizhe Wang, Junjian Jiang, Min Xing, Hongru Su","doi":"10.21037/tcr-24-743","DOIUrl":"10.21037/tcr-24-743","url":null,"abstract":"<p><strong>Background: </strong>Necroptosis, an alternative mode of programmed cell death (PCD) that overcomes apoptosis resistance, has been implicated in the progression and drug resistance of cancer. The aim of this study is to find the biological and prognostic significance of necroptosis in patients with head and neck squamous cell carcinoma (HNSCC).</p><p><strong>Methods: </strong>Integrated clinical datasets from The Cancer Genome Atlas (TCGA) HNSCC cohort underwent analysis. R package \"DESeq2\" was used to conduct differential gene expression analysis between normal and tumor tissues in the cohort, resulting in the identification of 2,172 differentially expressed genes (DEGs). A total of 159 necroptosis-related genes (NRGs) were extracted and performed a Venn analysis to identify the optimal necroptosis-related DEGs, resulting in the selection of 25 genes specifically associated with necroptosis in HNSCC. Then prognostic analyze, Cox regression analysis and prognostic model were demonstrated the ability to predict the extent of immunological infiltration in HNSCC.</p><p><strong>Results: </strong>Among these DEGs, five genes (<i>FADD, H2AZ1, PYGL, JAK3</i>, and <i>ZBP1</i>) were found to have prognostic value (P<0.05). Then, bioinformatic analyses were conducted, and the biological and clinical significance of these five genes were demonstrated. Furthermore, Cox regression analysis was performed to develop a prognostic gene model based on these genes, which effectively classified HNSCC patients into low- or high-risk groups. The prognostic model also demonstrated the ability to predict the extent of immunological infiltration in HNSCC. Additionally, a predictive nomogram based on the clinicopathological features of these five prognostic DEGs was constructed.</p><p><strong>Conclusions: </strong>We performed a systematic bioinformatic analysis to identify necroptosis-related prognostic genes in HNSCC patients. These genes' prognostic value was synthesized into a predictive nomogram for forecasting HNSCC progression.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"340-353"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of systemic inflammatory response index with all-cause and malignant neoplasm mortality in patients with gastrointestinal disease.","authors":"Peng Wang, Hongwei Zhu, Shuyuan Jiang, Xiaolei Liu, Bing Gao, Wanfu Bai, Wei Xie, Guo Shao","doi":"10.21037/tcr-24-1491","DOIUrl":"10.21037/tcr-24-1491","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Apart from being a primary cause of morbidity and mortality globally, gastrointestinal (GI) disorders also contribute significantly to the cost of healthcare. In patients with GI diseases, the systemic inflammatory response index (SIRI) is not often used as a marker of systemic immune inflammation to assess mortality-associated risk from malignant neoplasms or all causes. Therefore, the objective of this study was to elaborate on the link between SIRI and all causes and malignant neoplasm mortality in patients with GI disorders.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Retrospective analysis was performed using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. Restricted cubic spline (RCS) plots and multivariate Cox proportional hazards regression were used to examine the relationship between SIRI and GI patient mortality from malignant neoplasms and all causes. Data on survival were shown using Kaplan-Meier (KM) survival curves, and these correlations were further explored by subgroup and interaction analyses. Receiver operating characteristic (ROC) curves were generated to evaluate the specificity and sensitivity of SIRI in predicting mortality among patients with GI diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;This study included 4,137 GI patients who were followed comprehensively over 20 years, during which 165 malignant neoplasm mortality and 713 all-cause mortalities were recorded. A nonlinear association between all-cause mortality and SIRI was observed, whereas in GI patients, a linear relationship was identified between SIRI and cancer-related death. The hazard ratio (HR) was 1 at a SIRI level of 1.114, indicating the low-to-high mortality risk change. Participants in the highest quartile (Q4) in the fully adjusted model (model 3) showed a significantly greater likelihood of death from both malignant neoplasms and all-cause relative to those in the lowest quartile (Q1). The mortality HR for malignant neoplasms was 1.74 [95% confidence interval (CI): 1.08-2.82], whereas the HR for all-cause mortality was 2.50 (95% CI: 1.95-3.20). Furthermore, subgroup analysis revealed that higher SIRI was linked with a higher malignant neoplasm mortality risk among male, low-income, smoking, and drinking GI patients. Comparing SIRI to the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), the ROC curve analysis showed that SIRI had better diagnostic effectiveness. Interaction study verified that SIRI is an independent variable that significantly increases the probability of death from both all-cause and malignant neoplasms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The nonlinear positive correlation between the SIRI and the mortality from malignant neoplasms and all-cause in GI patients is highlighted by this study. Elevated SIRI levels were significantly linked to a higher mortality rate from GI disorders, including malignant neoplasms and ","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"272-285"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459616","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}