Journal of Cancer最新文献

{"title":"Network Pharmacology and Experimental Validation-based Investigation of the Underlying Mechanism of Yi-Yi-Fu-Zi-Bai-Jiang-San of Nasopharyngeal Carcinoma.","authors":"Zehua Lin, Ting Huang, Baoai Han, Zezhang Tao, Xiong Chen","doi":"10.7150/jca.109758","DOIUrl":"https://doi.org/10.7150/jca.109758","url":null,"abstract":"<p><p>Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) is a representative traditional Chinese medicine (TCM) formula. However, its potential anti-tumor effects in nasopharyngeal carcinoma (NPC) remains unclear. This study aims to investigate the monomers of YYFZBJS and their associated targets in the treatment of NPC. The primary active compounds of YYFZBJS and their corresponding targets were identified using the TCMSP, SEA, and Super-PRED databases. NPC-related target proteins were retrieved from OMIM, GeneCards, and TTD databases. A protein-protein interaction network was constructed using the common target proteins of YYFZBJS active compounds and NPC. Core genes were identified through three algorithms in CentiScape 2.2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then performed on these core genes. Validation was conducted using the GSE53819 and GSE13597 datasets. Finally, interactions between core targets and active ingredients were confirmed through molecular docking, molecular dynamics simulations, and cell-based experiments. A total of 715 corresponding to YYFZBJS active compounds and 3159 NPC-related targets were screened. Among these, 143 intersection genes were identified, from which 32 core genes were selected based on degree centrality, closeness centrality, and betweenness centrality. GO and KEGG analyses of these core genes revealed relevant biological processes and pathways. Furthermore, these 32 core genes were cross-referenced with the GSE53819 and GSE13597 datasets, identifying PTGS2 and CCND1 as valid targets of active compounds. Molecular docking, molecular dynamics simulations and cell experiments confirmed the effectiveness of the Acacetin-PTGS2 pathway. Acacetin of the main active ingredient in YYFZBJS suppressed NPC by downregulating PTGS2 expression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2212-2232"},"PeriodicalIF":3.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles-miR-205-5p inhibits lymphatic metastasis in pancreatic cancer through diffusely downregulating VEGFA.","authors":"Yuanyang Wang, Cheng Qin, Yutong Zhao, Bangbo Zhao, Zeru Li, Tianyu Li, Xiangyu Zhang, Weibin Wang","doi":"10.7150/jca.110659","DOIUrl":"https://doi.org/10.7150/jca.110659","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is to become the second leading cause of cancer-related death by 2040. Many factors contribute to this dilemma, including lymphatic metastasis, which is the primary cause of PDAC metastasis. The inhibition of early lymph node metastasis, including the lymphangiogenic process, may be a novel strategy for PDAC treatment. Through miRNA sequencing of plasma extracellular vesicles (EVs) from PDAC patients, for the first time, we identified that plasma EV-miR-205-5p served as a non-invasive biomarker distinguishing lymphatic metastasis status (N0 vs. N2) in PDAC patients. Using tissue microarray and <i>in situ</i> hybridization, we discovered that miR-205-5p was highly expressed in PDAC, but negatively correlated with lymph node metastasis. By <i>in vivo</i> and <i>in vitro</i> experiments, we demonstrated its unique mechanism of action via EV-mediated transfer to human lymphatic endothelial cells (HLECs), leading to systematic downregulation of VEGFA and inhibition of the Akt/Erk pathway, which suppressed lymphangiogenesis. Delivering miR-205-5p via engineered EVs might be a promising strategy to eliminate PDAC lymphatic metastasis and improve prognosis.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2197-2211"},"PeriodicalIF":3.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC16A1 Inhibits Ferroptosis and Promotes the Progression of Head and Neck Squamous Cell Carcinoma.","authors":"Huaiyuan Zong, Luyao Teng, Lifang Chen, Jianxin Qiu, Chunhui Tian","doi":"10.7150/jca.110217","DOIUrl":"https://doi.org/10.7150/jca.110217","url":null,"abstract":"<p><p>The solute carrier family 16 member 1 (SLC16A1) gene demonstrates abnormally elevated expression levels in a variety of human malignant tumors, and it is pivotal in tumor initiation and progression. Nonetheless, the precise mechanisms through which this gene operates in head and neck squamous cell carcinoma (HNSCC) need to be elucidated. This study integrated bioinformatics analysis with clinical patient samples to elucidate that the mRNA and protein levels of SLC16A1 were significantly upregulated in patients with HNSCC, which was closely associated with poor patient prognosis. In addition, through the construction of stable SLC16A1 knockdown and overexpression models in HNSCC cells along with <i>in vitro</i> and <i>in vivo</i> experiments, the study comprehensively illuminated the pivotal role of SLC16A1 in promoting the proliferation, migration, and invasiveness of HNSCC cells, as well as enhancing their resistance to ferroptosis. <i>In vitro</i> experimental results demonstrated that when SLC16A1 was knocked down, the proliferation, migration, and invasion capabilities of HNSCC cell lines were significantly reduced and the extent of RAS-selective lethal 3-induced lipid peroxidation increased compared with control cells. Conversely, HNSCC cell lines overexpressing SLC16A1 exhibited enhanced proliferation, migration, and invasion capabilities, accompanied by lower levels of lipid peroxidation. <i>In vivo</i> experiments further corroborated the pivotal role of SLC16A1 in promoting HNSCC tumor growth. Our research findings indicate that SLC16A1 acts as an oncogene in HNSCC, and that abnormally high expression of SLC16A1 significantly accelerates the development and progression of HNSCC by conferring resistance to ferroptosis.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2184-2196"},"PeriodicalIF":3.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: CCT8 promotes cell migration and tumor metastasis in lung adenocarcinomas: Erratum.","authors":"Zhiqiang Wu, Liyuan Deng, Jin Tao, Yuhai Lu, Xiaofei Zeng, Weikun Jia, Hu Chen","doi":"10.7150/jca.113359","DOIUrl":"https://doi.org/10.7150/jca.113359","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/jca.87983.].</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2182-2183"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Overexpression of TMEFF1 in Endometrial Carcinoma and the Mechanism Underlying its Promotion of Malignant Behavior in Cancer Cells: Erratum.","authors":"Xin Nie, Lingling Gao, Mingjun Zheng, Caixia Wang, Shuang Wang, Xiao Li, Yue Qi, Liancheng Zhu, Juanjuan Liu, Bei Lin","doi":"10.7150/jca.113036","DOIUrl":"https://doi.org/10.7150/jca.113036","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/jca.58524.].</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2181"},"PeriodicalIF":3.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Characterization of Oxidative Stress and Endoplasmic Reticulum Stress-Related Genes in Esophageal Cancer.","authors":"Xiaoxu Li, Juntao Lu, Yan Zhao, Wei Guo","doi":"10.7150/jca.104376","DOIUrl":"https://doi.org/10.7150/jca.104376","url":null,"abstract":"<p><p>Increasing evidence highlights the critical roles of oxidative stress and endoplasmic reticulum (ER) stress in tumor initiation and progression. However, the specific functions of related genes in esophageal cancer (ESCA) remain poorly understood. To investigate the impact of oxidative and ER stress on ESCA, this study analyzed the TCGA and GEO databases to identify 12 oxidative stress- and ER stress-related differentially expressed genes (OERDEGs). Pathway analysis revealed significant enrichment in critical processes such as PRC2-mediated methylation, oxidative stress-induced senescence, and NOTCH signaling. A novel LASSO regression model was developed to link gene expression with clinical prognosis, and the model was validated through ROC and Cox regression analyses. Four OERDEGs (CDKN3, PINK1, SPP1, and TFRC) were identified as key biomarkers for ESCA prognosis. Notably, TFRC expression was significantly upregulated in ESCA cells under both oxidative and ER stress conditions, in a dose- and time-dependent manner. Functional assays confirmed that TFRC promotes cell proliferation, migration, and invasion by regulating the HIF-1α and NOTCH1 signaling pathways. This study elucidates the complex interplay between oxidative/ER stress and ESCA progression and highlights the innovative application of bioinformatics to identify potential biomarkers for early diagnosis and therapeutic strategies. Targeting TFRC, in particular, may offer a novel approach to improving ESCA treatment and enhancing patient prognosis.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2103-2123"},"PeriodicalIF":3.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vessel sign analysis paves the way to optimized CBCT application in interventional pulmonology: COMBINED algorithm as a one-stop-shop.","authors":"Wolfgang Hohenforst-Schmidt, Ying Xu, Julia Greeven, Sander Langereis, Haidong Huang, Jian Liu, Xiaopeng Yao, Xiaping Shen, Yang Yang, Liangquan Wu, Paul Zarogoulidis, Stamatis Petousis, Chrysoula Margioula-Siarkou, Dimitris Petridis, Michael Steinheimer, Andreas Riedel, Noufal Aboobaker, Evaggelos Karamitrousis, Eleni-Isidora Perdikouri, Anastasios Vagionas, Thomas Vogl, Anil Sinha","doi":"10.7150/jca.109996","DOIUrl":"https://doi.org/10.7150/jca.109996","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; We used CBCT application as one-stop-shop nodule orientated approach in regards to increase DY, reduce complication rate, reduce time on-table and economical costs with classical peripheral instruments including mini-cryoprobe (ERBE 1,1mm), rEBUS (Olympus) and standard RUFBs (Olympus Company) with at least 2mm working channel and 4,2mm outer diameter for the diagnosis of peripheral targets (iSPNs) in a prospective all-comers registry after detailed analysis of pre-interventional CT for vessel- and bronchus sign classes. &lt;b&gt;Materials and Methods:&lt;/b&gt; From Jun 2017 until Nov 2019 in 90 all-comers patients between 16 and 95 years fit for bronchoscopy with 101 peripheral lesions in a daily routine scheme after informed consent about this prospective registry were included. For histological proven benign disease in any lesion patients had to adhere FU according radiological guidelines and further on by re-visits for at least 2 years after biopsy resulting into last visit in Feb 2022 without any drop-out. Present HRCT was mandatory to achieve one day before intervention. It had to be decided by the examiner mainly after analysis of the preset HRCT which of the 3 CBCT driven modalities were used for diagnostical approach: A) Pure endobronchial approach (CBCT, rEBUS, TBB), B) Pure transthoracical approach with a 21G core-biopsy needle (BIOPINCE needle) with CBCT only, or C) Combined approach as described below (CBCT, rEBUS, TTNA). As instruments were available common forceps and needles, EWC, curette and various RUFB (Olympus Company) mentioned in the materials section. A second CBCT was only allowed in the combined approach group to plan the 3D transthoracic approach in expiration whereas even a CBCT for tool-in-lesion control (TIL CBCT) was never allowed in all 3 groups. &lt;b&gt;Results:&lt;/b&gt; In 100 lesions predefined modalities pure endobiopsy, pure TTNA and combined approaches were performed in 77, 9 and 14 lesions respectively without any pneumothorax or bleeding. In these 3 modalities we found confirmed (mostly specific) benign and malignant cases 47 and 30, 4 and 5, 2 and 12 respectively. Lesion sizes in the 3 different groups were (median, mean) 14 and 17,7mm (of those 41 invisible of 77 under XR (53%) in the pure endobiopsy group), 27 and 31mm (11% invisible under XR in the pure TTNA group), 18,5 and 23mm (35% invisible under XR in the combined group) respectively. In the 3 groups for the malignant cases 25 of 30, 5 of 5 and 12 of 12 were diagnosed correctly rendering a diagnostical yield of 42 in 47 malignant cases for the whole algorithm (89,4%) with sizes (mean, median) for the whole algorithm of 16 and 19,7mm respectively which is comparable to published data for robotic-assisted bronchoscopy yield. In regards to vessel sign analysis it has to be clearly stated that the significance level for outcome prediction is inferior to bronchus sign analysis. In multivariate analysis there was a clear tendency towards higher outco","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2124-2144"},"PeriodicalIF":3.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis of DLAT reveals it as a prognostic Biomarker involved in immune infiltration of liver hepatocellular carcinoma.","authors":"Haitao Xu, Yiqun Ma, Lishi Shao, Yao Fu, Bosheng Luo, Chunjuan Xia, Xiaoli Min","doi":"10.7150/jca.102256","DOIUrl":"https://doi.org/10.7150/jca.102256","url":null,"abstract":"<p><p><b>Background:</b> Dihydrolipoamide S-acetyltransferase (DLAT) is one of the cuproptosis-related genes (CRGs). Increasing evidence suggests that DLAT plays a critical role in various cancers. However, information about its functions and potential mechanisms in liver hepatocellular carcinoma (HCC) is still limited. <b>Methods:</b> Bioinformatics analysis were used to evaluate the potential association of DLAT expression with N6-methyladenosine (m6A) modification, clinical features, survival prognosis, biological functions, immune infiltration, and immune checkpoint molecules (ICM) in tumor patients. In addition, the expression of DLAT in HCC tissues was verified using immunohistochemistry (IHC). <b>Results:</b> The aberrant expression of DLAT had a significant impact on the prognosis of patients with various tumors. Importantly, DLAT expression was strongly associated with immune cell infiltration and immune checkpoint molecules (ICM) in tumors. For the first time, we found a significant positive correlation between DLAT expression and m6A regulatory factors in liver cancer, and that DLAT is associated with the PLK1 pathway, PI3K-AKT signaling pathway, Notch signaling pathway, WNT signaling pathway, and Aurora B pathway. <b>Conclusions:</b> Our results showed a significant increase in DLAT expression in HCC. Furthermore, the prognosis of patients with high DLAT expression was poor. Importantly, DLAT was correlated with immune cell infiltration and immune checkpoint molecules in HCC patients. Together, our results indicate that DLAT represents a promising therapeutic target for HCC patients.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2167-2180"},"PeriodicalIF":3.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of Prognostic Genes Related to Histone Lactylation Modification in Glioblastoma: An Integrated Analysis of Transcriptome and Single-cell RNA Sequencing.","authors":"Wenfeng He, Ruihong Chen, Guangliang Chen, Lihan Zhang, Yuhang Qian, Jie Zhou, Jianhua Peng, Vincent Kam Wai Wong, Yong Jiang","doi":"10.7150/jca.110646","DOIUrl":"https://doi.org/10.7150/jca.110646","url":null,"abstract":"<p><p><b>Background:</b> The impact of histone lactylation modification (HLM) on glioblastoma (GBM) progression is not well understood. This study aimed to identify HLM-associated prognostic genes in GBM and explore their mechanisms of action. <b>Methods:</b> The presence and role of lactylation in glioma clinical tissue samples and its correlation with GBM progression were analysed through immunohistochemical staining and Western blotting. Sequencing data for GBM were obtained from publicly available databases. An initial correlation analysis was performed between global HLM levels and GBM. Differentially expressed HLM-related genes (HLMRGs) in GBM were identified by intersecting differentially expressed genes (DEGs) from the TCGA-GBM dataset, key module genes derived from weighted gene coexpression network analysis (WGCNA), and previously reported HLMRGs. Prognostic genes were subsequently identified through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses, which formed the basis for constructing a risk prediction model. Associations between HLMRGs and GBM were further evaluated via single-cell RNA sequencing (scRNA-seq) datasets. Complementary analyses, including functional enrichment, immune infiltration, somatic mutation, and nomogram-based survival prediction, were conducted alongside in vitro experiments. Additionally, drug sensitivity and Chinese medicine prediction analyses were performed to identify potential therapeutic agents for GBM. <b>Results:</b> We detected a significant increase in global lactylation levels in GBM, which correlated with patient survival. We identified 227 differentially expressed HLMRGs from the intersection of 3,343 differentially expressed genes and 948 key module genes, indicating strong prognostic potential. Notably, genes such as SNCAIP, TMEM100, NLRP11, HOXC11, and HOXD10 were highly expressed in GBM. Functional analysis suggested that HLMRGs are involved primarily in pathways related to cytokine‒cytokine receptor interactions, cell cycle regulation, and cellular interactions, including microglial differentiation states. Further connections were established between HLMRGs and infiltrating immune cells, particularly type 1 T helper (Th1) cells, as well as mutations in genes such as PTEN. The potential therapeutic agents identified included ATRA and Can Sha. <b>Conclusion:</b> The HLM-related gene risk prediction model shows substantial promise for improving patient management in GBM, providing crucial insights for clinical prognostic evaluations and immunotherapeutic approaches in GBM.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2145-2166"},"PeriodicalIF":3.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol metabolism-related genes predict immune infiltration and prognosis in gastric cancer patients.","authors":"Wenxuan Liu, Li Liu, Tianrui Kuang, Wenhong Deng","doi":"10.7150/jca.104389","DOIUrl":"https://doi.org/10.7150/jca.104389","url":null,"abstract":"<p><p><b>Background:</b> Gastric cancer (GC) is one of the most prevalent malignant diseases worldwide. Abnormal metabolic reprogramming, particularly cholesterol metabolism, influences tumor development and treatment outcomes. This study investigates the predictive and functional significance of cholesterol metabolism-related genes in gastric cancer patients. <b>Methods:</b> Clinical and gene expression data related to cholesterol metabolism in gastric cancer were analyzed using datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A predictive signature was developed and validated using LASSO, Cox regression, and the GSE26889 cohort, followed by evaluation with Kaplan-Meier analysis. A nomogram was constructed by integrating the signature with clinical factors and ssGSEA for immunological analysis. The role of NPC2 was investigated using western blot, qPCR, and cellular assays. <b>Results:</b> We conducted a bioinformatics analysis of 50 genes associated with cholesterol metabolism in gastric cancer. Using the GEO and TCGA datasets, we identified 28 genes with differential expression in gastric cancer patients. Subsequent COX univariate and LASSO regression analyses of these 28 DEGs identified five genes (APOA1, APOC3, NPC2, CD36, and ABCA1) as independent prognostic risk factors. We then constructed a risk model for cholesterol metabolism genes, revealing that survival was worse in the high-risk group compared to the low-risk group, with more severe case staging outcomes. We conducted a comparative analysis of immune cells between the high-risk and low-risk groups, revealing distinct variations in immune cell type expression. We then developed a model using a correlation nomogram to illustrate these conclusions. We further examined the biological characteristics of NPC2. Immunohistochemistry and qPCR results showed that NPC2 exhibited significant protein and mRNA expression in gastric cancer tissues. We used siRNA technology to suppress NPC2, resulting in reduced viability, proliferation, and invasion capacity of gastric cancer cells, as determined by CCK-8, colony formation, wound healing, and Transwell assays. <b>Conclusion:</b> A risk signature comprising five cholesterol metabolism-related genes was constructed using bioinformatics to estimate outcomes and therapeutic responses in gastric cancer patients. The results suggest that NPC2 may serve as a novel biomarker for gastric cancer patients.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 7","pages":"2087-2102"},"PeriodicalIF":3.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}