Translational cancer research最新文献

{"title":"Potential therapeutic targets for colorectal cancer and its subsites: evidence from the proteome-wide Mendelian randomization analyses.","authors":"Jinyi Li, Yuanda Liu, Chang Liu, Pengtuo Xiao","doi":"10.21037/tcr-24-1503","DOIUrl":"10.21037/tcr-24-1503","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the most common malignant tumor of the digestive tract worldwide, however, the potential targets for CRC and its subsites (colon cancer & rectum cancer) are less known. The aim of this study is to explore potential therapeutic targets for CRC.</p><p><strong>Methods: </strong>A proteome-wide genome-wide association studies (GWAS) in 35,559 Icelanders with 4,907 plasma proteins was used as instrumental variables (P value <5×10^-8). The discovery stage consisted of the CRC GWAS with the largest sample size (CRC: 14,886 cases; colon: 3,793 cases; rectum: 2,091 cases). The significant proteins were further validated in the FinnGen study with 5,458 CRC cases (3,292 colon + 2,017 rectum). We identified relevant protein loci in CRC by two sample Mendelian randomization (MR) [false discovery rate (FDR) <0.05], colocalization analysis was used to further determine the relevance between CRC and plasma proteins, enrichment analysis and drug prediction were used to predict protein function.</p><p><strong>Results: </strong>A total of 31 proteins were found to be in robust causal associations with CRC and the proteins' effects displayed anatomic site-specificity in MR analysis. The subsequent colocalization analysis pinpointed that CHDRL2 had a shared region with CRC and its two subsites, suggesting the importance of targeting it. Besides, IGF2R and ENPEP displayed anatomic site-specificity to colon cancer while ASRGL1 was strongly correlated only with the risk of rectal cancer. Enrichment analysis revealed functions of these proteins in CRC, and DrugBank showed their target drug.</p><p><strong>Conclusions: </strong>In summary, our study has identified a common protein, CHDRL2, as the drug targets for CRC and its subsites. Besides, IGF2R and ENPEP displayed anatomic site-specificity to colon cancer while ASRGL1 was strongly correlated only with the risk of rectal cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"486-496"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459478","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":"Prognostic development and validation of a prediction model based on major histocompatibility complex-related differentially expressed genes in stomach adenocarcinoma.","authors":"Tianqi Wang, Yiran Liu, Shengjie Ma, Binxu Qiu, Quan Wang","doi":"10.21037/tcr-24-707","DOIUrl":"10.21037/tcr-24-707","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Stomach adenocarcinoma (STAD) is a common malignant tumor with high morbidity and mortality. Major histocompatibility complex (MHC) is an important component of the immune system responsible for antigen presentation. However, no studies have yet reported on the relationship between major histocompatibility complex-related differentially expressed genes (MHCRDEGs) and the survival prognosis of STAD. The aim of this study is to explore the relationship between MHCRDEGs and survival prognosis in STAD patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Using The Cancer Genome Atlas (TCGA) database, we screened for differentially expressed MHCRDEGs, and a survival prognosis model was constructed based on these genes. We generated training and validation samples from the TCGA and Gene Expression Omnibus (GEO) datasets to enhance the robustness of our findings. The predictive effects of the model were assessed using Kaplan-Meier (KM) survival curve analysis, receiver operating characteristic (ROC) curve analysis, calibration analysis and decision curve analysis (DCA), with statistical significance reported as P values. The differences in the expression of key MHCRDEGs between different subgroups of TCGA and GEO databases were analyzed. Finally, a multifactorial survival prognostic model was constructed by combining MHC score (MHCs), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the expression of key genes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We identified five key MHCRDEGs: &lt;i&gt;MKI67&lt;/i&gt;, &lt;i&gt;MYB&lt;/i&gt;, &lt;i&gt;SERPINE1&lt;/i&gt;, &lt;i&gt;TRIM31&lt;/i&gt;, and &lt;i&gt;HAVCR1&lt;/i&gt;. In the first prognostic model, the KM curves demonstrated a highly statistically significant difference in predicting overall survival (OS) in patients (P&lt;0.001). The ROC curves indicated that the model showed relatively low accuracy in predicting 1-year [area under curve (AUC) =0.616], 3-year (AUC =0.644), and 5-year (AUC =0.619) occurrence. Furthermore, calibration analysis and DCA suggested that the model's predictions of OS were consistent with the actual patient survival, with the 5-year prognostic model exhibiting the best clinical utility. In the TCGA and GEO datasets, most of the key genes showed significant expression differences between the STAD/GEO and normal groups (P&lt;0.001). Finally, the predictive model constructed by combining MHCs with clinicopathological staging demonstrated good predictive accuracy with optimal clinical utility at 5 years, with specific accuracy metrics provided as part of our results, and validated their expression via qRT-PCR in cell lines (&lt;i&gt;MKI67&lt;/i&gt;: P=0.01, &lt;i&gt;MYB&lt;/i&gt;: P=0.02, &lt;i&gt;SERPINE1&lt;/i&gt;: P=0.02, &lt;i&gt;TRIM31&lt;/i&gt;: P=0.02, &lt;i&gt;HAVCR1&lt;/i&gt;: P&lt;0.0001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this study, the expression and distribution of MHCRDEGs in STAD were analyzed by various methods, and a clinical prediction model of STAD was constructed using MHCRDEGs. The validity of this model confirms the feasibil","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 1","pages":"33-61"},"PeriodicalIF":1.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459479","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":"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":"<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":"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}