Journal of Cancer最新文献

{"title":"Multi-Omics Analysis Reveals the transforming growth factor-β Signaling-Driven Multicellular Interactions with Prognostic Relevance in Cervical Cancer Progression.","authors":"Yuhan Wang, Guangxu Cao, Huimin Zeng, Yong Zhi, Mengting Xu, Ying Wang, Min Liu, Yetian Ruan, Ka Yu Tse, Qingfeng Zhang, Jinli Gao, Zhiqiang Han, Fang Li","doi":"10.7150/jca.114505","DOIUrl":"https://doi.org/10.7150/jca.114505","url":null,"abstract":"<p><p>While cervical cancer (CC) prognosis depends on tumor staging, the spatiotemporal evolution of tumor microenvironment (TME) heterogeneity during metastatic progression remains poorly characterized at single-cell resolution. We employed an integrative multi-omics approach, combining single-cell RNA sequencing (scRNA-seq; n = 11), spatial transcriptomics (ST), and bulk RNA-seq data from the TCGA-CESC cohort (n = 304), to systematically map TME remodeling across CC progression stages. scRNA-seq was performed on primary lesions from patients with localized (n = 3), regional (n = 4), and metastatic (n = 4) diseases, with in-depth analyses focusing on cellular characteristics, cell type composition alterations, functional changes, differentiation trajectories, and cell-cell interaction networks. These findings were further validated using spatial transcriptomics, bulk RNA-seq data, and multiple immunohistochemistry (mIHC) experiments. ScRNA-seq data revealed that the TME of the metastatic group displayed a distinct immunosuppressive phenotype. Three key subclusters closely linked to TME remodeling in this group were identified. Notably, a novel metastasis-associated epithelial subpopulation (Epi0_AGR2), characterized by both epithelial-mesenchymal transition (EMT) and chemokine secretory phenotypes, was discovered. Gene Set Variation Analysis (GSVA) revealed that transforming growth factor β (TGF-β) signaling activation served as its primary transcriptional driver. Additionally, a neutrophil subset with pro-tumor and immunosuppressive properties, as well as a cancer-associated fibroblasts (CAFs) subset that promoted angiogenesis, were enriched in the metastatic group. Cell-cell interaction analysis and spatial mapping further revealed the formation of coordinated Epi0-neutrophil-CAFs niches, which established TGF-β-CXCL1/2/8-OSM/OSMR feedforward loops. Importantly, a computational model derived from the TME metastatic niche signature demonstrated significant prognostic stratification in the TCGA cohort (HR = 2.5179, p = 0.0144). In all, this study provides the first comprehensive delineation of stage-specific TME dynamics in CC, revealing TGF-β-driven cellular cooperativity as a metastatic switch. The joint framework establishes a potential clinically translatable tool for precision prognosis and therapeutic targeting.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2857-2876"},"PeriodicalIF":3.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626479","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":"MFAP2 promotes the progress of esophageal squamous cell carcinoma by enhancing PTGS2 signaling.","authors":"Zidong Chu, Pengyu Pan, Shaoyan Qi, Sujuan Fang, Zhe Zhang, Zhenguo Cheng, Baisui Feng","doi":"10.7150/jca.106659","DOIUrl":"https://doi.org/10.7150/jca.106659","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies, accounting for over 85% of all esophageal cancers worldwide and over 90% in China. Due to the absence of effective early diagnostic tools and therapeutic approaches, the 5-year survival rate remains below 30%. Thus, it is crucial to further investigate the molecular mechanisms underlying ESCC. By analyzing differentially expressed genes in esophageal adenocarcinoma (EAC) and ESCC, we identified 127 genes that were significantly upregulated in ESCC and enriched in extracellular matrix organization. Notably, MFAP2 (microfibril associated protein 2), a matrix-related molecule with unclear function, was found to be highly expressed in ESCC in both the TCGA database and our RNA sequencing data. Its elevated levels were associated with cancer progression. Western blot, immunofluorescence, and immunohistochemistry revealed that MFAP2 protein was highly expressed in ESCC and predominantly distributed in the extracellular matrix, cytoplasm, and partially in the nucleus. <i>In vitro</i> functional experiments demonstrated that overexpressing MFAP2 had no significant effect on cell proliferation but inhibited cell migration and invasion. <i>In vivo</i> xenograft assays showed that MFAP2 enhanced the growth of the KYSE-450 cancer cell line, though no statistical difference was observed in KYSE-140. Bioinformatics analysis revealed a positive correlation between MFAP2 expression and anti-tumor (M1 type) macrophages in EAC tissues, whereas in ESCC tissues, MFAP2 correlated positively with non-activated (M0 type) macrophages. RNA sequencing indicated that MFAP2 is involved in immune pathways and can promote PTGS2 expression. Collectively, this study preliminarily evaluates the function and potential molecular mechanism of MFAP2 in ESCC, offering new therapeutic targets and ideas for ESCC treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2846-2856"},"PeriodicalIF":3.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626477","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: Androgen Receptor Promotes Gastric Carcinogenesis via Upregulating Cell Cycle-Related Kinase Expression: Erratum.","authors":"Ren Wang, Xiao-Yi Xu, Hong Zhu, Xiong Liang, Xue Li, Ming-Xu Jia, Qing-Hua Wang, Hui-Yun Wang, Xiao-Xing Li, Gui-Jun Zhao","doi":"10.7150/jca.117489","DOIUrl":"https://doi.org/10.7150/jca.117489","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/jca.34430.].</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2841-2845"},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626449","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: Ethanol Extracted from Radix of Actinidia Chinensis Inhibits Human Colon Tumor Through Inhibiting Notch-signaling Pathway: Erratum.","authors":"Wanle Hu, Chenchen Wu, Chenchen Yuan, Minyuan Chen, Chun Jin, Chenguo Zheng","doi":"10.7150/jca.117445","DOIUrl":"https://doi.org/10.7150/jca.117445","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/jca.51275.].</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2837-2840"},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626450","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":"S-palmitoylation: a novel insight in the development and immunotherapy of oral squamous cell carcinoma.","authors":"Xue-Ting Yuan, Jing-Ru Wang, Ying Yang, Jian-Gang Ren","doi":"10.7150/jca.110721","DOIUrl":"https://doi.org/10.7150/jca.110721","url":null,"abstract":"<p><p>S-palmitoylation (hereinafter referred to as palmitoylation) is a reversible lipid modification that has recently received considerable attention in cancer research. Despite its known association with tumour progression and treatment response, it remains unclear how palmitoylation could be targeted for enhancing therapeutic outcomes in oral squamous cell carcinoma (OSCC). This review summarises palmitoylated proteins common in various cancers and highlights emerging targets specific to OSCC, emphasising their roles in protein stability, signalling pathways, and cellular behaviour. Additionally, we explore new trends in targeting palmitoylated proteins to manage cancer progression and bolster the immune response in OSCC. Furthermore, this review highlights existing knowledge gaps and calls for detailed investigations into OSCC-specific palmitoylation mechanisms, including the expression levels of palmitoylated proteins and palmitoylation enzymes and their effect on OSCC signalling pathways.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2787-2799"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626483","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":"Integrated machine learning based on cuproptosis and RNA methylation regulators to explore the molecular model of prostate cancer and provide novel insights to immunotherapy.","authors":"Junchao Wu, Wentian Wu, Jiaxuan Qin, Ziqi Chen, Rongfang Zhong, Xunkai Zhu, Jialin Meng, Peng Guo, Song Fan","doi":"10.7150/jca.112843","DOIUrl":"10.7150/jca.112843","url":null,"abstract":"<p><p><b>Background:</b> As a highly prevalent tumor in males, prostate cancer (PCa) needs newly developed biomarkers to guide prognosis and treatment. However, few researches have elaborated on the function of cuproptosis-associated RNA methylation regulators (CARMRs). <b>Methods:</b> We identified CARMRs based on single-sample gene set enrichment analysis and weighted gene co-expression network analyses. Subsequently, we performed 10 machine learning algorithms and 101 combinations of them to select the best model in TCGA, GSE70768, GSE70769, and DKFZ cohorts. Furthermore, we explored the potential function of CARMRs in the tumor microenvironment, immunotherapy, and tumor mutation burden (TMB). We validated the expression of the two genes with the largest regression coefficients using qRT-PCR. <b>Results:</b> In our analysis, we successfully established a consensus prognostic model with 9 CARMRs based on the 101-machine learning framework. Furthermore, functional enrichment analysis revealed different metabolic and signaling pathways in the high- and low-risk groups. Notably, the high-risk group had a higher TMB, a lower level of immune infiltration, and a lower expression of immune checkpoints. Through drug sensitive analysis, we screened chemotherapy drugs suitable for different groups. Vitro experiments illustrated the high expression of C4orf48 and SLC26A1 in PCa compared with normal controls. The discovery was in concordance with bioinformatic analysis results. <b>Conclusion:</b> A gene signature with 9 CARMRs was developed in our study, which served as biomarkers for PCa. This brings benefits in determining the prognosis of patients with PCa and guiding personalized treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2762-2777"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325854","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":"TACE Empowers Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors in Unresectable HCC: A Multicenter Retrospective Study.","authors":"Yu Lei, Yaowei Bai, Xiatong Bai, Jiacheng Liu, Bo Sun, Wenlong Wu, Xiaoling Zhi, Yang Su, Hongsen Zhang, Chuansheng Zheng","doi":"10.7150/jca.112706","DOIUrl":"10.7150/jca.112706","url":null,"abstract":"<p><p><b>Purpose</b>: The aim of this multicenter retrospective study was to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) in treating advanced hepatocellular carcinoma (HCC) compared to treatment with TKI and ICI alone. <b>Methods</b>: The study included 286 patients with advanced HCC, of which 210 were treated with TACE, TKI, and ICI (TACE+T+I group) and 76 with TKI and ICI alone (T+I group). Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR) were assessed. A nomogram was developed to stratify patients into high-risk and low-risk groups based on their one-year and two-year survival probabilities. <b>Results</b>: Patients in the TACE+T+I group demonstrated significantly longer PFS (8.4 months vs. 4.0 months, Log-rank <i>P</i> = 0.0016) and median OS (14.5 months vs. 10.0 months, Log-rank <i>P</i> < 0.0001) compared to the T+I group. Additionally, the TACE+T+I group had a higher ORR (56.7% vs. 21.1%, <i>P</i> = 0.002) and DCR (84.3% vs. 72.4%, <i>P</i> = 0.023). Both groups exhibited good tolerance to adverse events. A nomogram incorporating factors such as therapeutic strategy, prothrombin time (PT), age, and tumor size effectively categorized patients into low- and high-risk groups with notably different survival outcomes. <b>Conclusion</b>: These findings suggest that TACE combined with TKI and ICI significantly improved survival outcomes and showed good safety compared to TKI and ICI alone in the treatment of advanced HCC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2750-2761"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325857","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":"Stanniocalcin-2 significantly promotes colorectal cancer progression by regulating cancer cell proliferation and invasion.","authors":"Fang Li, Zihao Liu, Kaibin Huang, Shunkai Ding, Chang Zhu, Yuxiang Fu, Xiao Sun, Shipai Zhang, Rui Zhang, Zhipeng Jiang, Keli Zhong, Qijun Zheng","doi":"10.7150/jca.101892","DOIUrl":"10.7150/jca.101892","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Our study delves into the molecular intricacies of CRC by analyzing gene expression profiles across multiple datasets, revealing significant gene alterations that distinguish CRC from normal tissues. We identified Stanniocalcin-2 (STC2) as a key regulator in CRC, associated with poor prognosis, survival outcomes and cancer cell proliferation or invasion. Through comprehensive data mining of the Gene Expression Omnibus (GEO), the European Bioinformatics Institute (EMBL-EBI), and The Cancer Genome Atlas (TCGA), we emphasized the role of STC2 in tumorigenesis. Our pan-cancer analysis established STC2's involvement in various cancer types, underscoring its potential as a universal biomarker. Additionally, we performed experimental research and found STC2 is significantly upregulated in CRC tissue and can promote CRC progression by regulating cancer cell invasion and proliferation. This study provides valuable insights into the oncogenic role of STC2, proposing it as a promising target for therapeutic intervention and a marker for aggressive cancer phenotypes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2737-2749"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325856","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 identifies DBF4B as an immunologic and prognostic biomarker.","authors":"Chongjiu Qin, Yu Chen, Haifei Qin, Xinlei Huang, Haixiang Xie, Kejian Yang, Junqi Liu, Xin Zhou, Xiwen Liao, Chuangye Han, Hao Su, Guohong Yan, Zuying Wan, Tao Peng, Guangzhi Zhu","doi":"10.7150/jca.109134","DOIUrl":"10.7150/jca.109134","url":null,"abstract":"<p><p>DBF4 zinc finger B (DBF4B) is a regulator of cellular CDC7 proteins, and the complex it forms with CDC7 proteins plays a key role in coordinating the initiation of DNA replication. Compared with previous DBF4B studies, this study is the first to use a publicly available database to explore DBF4B differential expression and prognosis in different cancers, as well as its association with gene mutations, molecular and immune subtypes, immune infiltration, methylation, and drug sensitivity. Our results showed that DBF4B was significantly differentially expressed in most cancer types as well as in cancers with different molecular and immune subtypes, and DBF4B was also significantly correlated with the prognosis of a subset of cancers. Furthermore, our analysis showed that DBF4B expression in liver hepatocellular carcinoma (LIHC) was associated with a variety of factors, including age, gender, race, height, weight, body mass index (BMI), presence of residual tumor, and tumor status. Elevated DBF4B expression was correlated with poorer overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). especially in different clinical subtypes. In conclusion, DBF4B may be a key molecular biomarker for pan-cancer immunology and prognosis and an independent prognostic risk factor for LIHC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2626-2648"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325868","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":"Diagnostic Value of Serum D-dimer, CA19-9, and CT Imaging Features in Pancreatic Ductal Adenocarcinoma and Benign Pancreatic Lesions.","authors":"Yuan Li, Yingying Cao, Yaping Zhang, Tao Zhou, Fan Xia, Shuai Ren, Zhongqiu Wang","doi":"10.7150/jca.111548","DOIUrl":"https://doi.org/10.7150/jca.111548","url":null,"abstract":"<p><p><b>Background:</b> The distinction between pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic lesions remains challenging. This study aimed to evaluate the utility of computed tomography (CT) imaging features and clinical characteristics in differentiating PDAC from benign pancreatic lesions. <b>Methods:</b> In this retrospective study, a total of 97 patients with PDAC and 90 patients with benign pancreatic lesions were included. Various imaging features and clinical characteristics were assessed. Univariable and multivariable logistic regression analyses were conducted, and receiver operating characteristic (ROC) curves and their corresponding areas under the curve (AUCs) were assessed. The optimal cut-off value for D-dimer was determined using the Youden index. The DeLong test was employed to compare the AUCs of the ROC curves between different prediction models. <b>Results:</b> The clinical and radiologic models achieved AUCs of 0.86 and 0.85, respectively. Moreover, the combined model demonstrated superior predictive performance compared to either model alone. This overall model included two significant clinical predictors (D-dimer and CA19-9) and three radiological predictors (lymph node enlargement, pancreatic atrophy, and cystic components). It yielded an AUC of 0.92 (95% CI: 0.88-0.95), with a sensitivity of 83.5% and specificity of 82.2%. In addition, the optimal cut-off value of D-dimer for differentiating PDAC from benign pancreatic lesions was found to be 0.84 mg/L. <b>Conclusions:</b> The overall model including clinical and radiologic variables (e.g., serum D-dimer, CA19-9, lymph node enlargement, pancreatic atrophy, and cystic components) demonstrated higher sensitivity and specificity in differentiating PDAC from benign pancreatic lesions. Serum D-dimer may serve as a valuable adjunctive biomarker in the diagnosis of pancreatic cancer and may further enhance the diagnostic performance of CA19-9 when used in combination.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2812-2821"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626448","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}