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Gastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subsequently, these genes were harnessed to construct a prognostic model, termed the Tumor Stemness Risk Genes Prognostic Model (TSRGPM). Through PCA, Cox regression analysis and ROC curve analysis, the efficacy of Tumor Stemness Risk Scores (TSRS) in stratifying patient risk profiles was underscored, affirming its ability as an independent prognostic indicator. Notably, the TSRS exhibited a significant correlation with lymph node metastasis in gastric cancer. Furthermore, leveraging algorithms such as CIBERSORT to dissect immune infiltration patterns revealed a notable association between TSRS and monocytes and other cell. Subsequent scrutiny of tumor stemness risk genes (TSRGs) culminated in the identification of CDC25A for detailed investigation. Bioinformatics analyses unveil CDC25A's implication in driving the malignant phenotype of tumors, with a discernible impact on cell proliferation and DNA replication in gastric cancer. Noteworthy validation through experiments corroborated the bioinformatics findings, elucidating the pivotal role of CDC25A expression in modulating tumor stemness in gastric cancer. In summation, the established and validated TSRGPM holds promise in prognostication and delineation of potential therapeutic targets, thus heralding a pivotal stride towards personalized management of this malignancy.
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http://dx.doi.org/10.18632/aging.205715 | DOI Listing |
Adv Sci (Weinh)
September 2025
China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Immune Response and Immunotherapy, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, GIBH-CUHK Joint Resea
TP53 mutations are highly associated with hepatocellular carcinoma (HCC), a common and deadly cancer. However, few primary drivers in the progression of HCC with mutant TP53 have been identified. To uncover tumor suppressors in human HCC, a genome-wide CRISPR/Cas9-based screening of primary human hepatocytes with MYC and TP53 overexpression (MT-PHHs) is performed in xenografts.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
Department of Urology, School of Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China.
Despite the expanding clinical application of second-generation anti-androgens like enzalutamide (ENZ) in hormone-sensitive prostate cancer (HSPC), therapeutic resistance culminating in castration-resistant prostate cancer (CRPC) persists as an unresolved clinical crisis. Through comprehensive single-cell transcriptomic profiling of ENZ-naïve and ENZ-treated tumors, an expansion of ENZ-resistant myofibroblastic cancer-associated fibroblast (designated STEAP4 myoCAF) is identified that correlates with adverse clinical outcomes. Strikingly, STEAP4 myoCAF demonstrated intrinsic ENZ resistance through a mechanistically novel pathway involving transcription factor binding to IGHM enhancer 3 (TFE3)-mediated autophagy activation.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
September 2025
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford, United Kingdom. Electronic address:
Cancer stem cells (CSCs) are central to tumour initiation, progression, and relapse, yet their dynamic and adaptive nature hampers therapeutic targeting. Once viewed as a fixed subpopulation, CSCs are now recognised as a fluid functional state that tumour cells can enter or exit, driven by intrinsic programs, epigenetic reprogramming, and microenvironmental cues. This plasticity complicates identification due to inconsistent marker expression and enables resistance, dormancy, and metastasis.
View Article and Find Full Text PDFStem Cells Int
August 2025
Department of Interventional Radiology, Affiliated Hospital of jiangnan University, Wuxi, China.
Liver hepatocellular carcinoma (LIHC) is a prevalent and highly aggressive form of liver cancer, characterized by increasing rates of incidence and mortality globally. Although numerous treatment options currently exist, they frequently result in insufficient clinical outcomes for those diagnosed with LIHC. This highlights the urgent need to identify new biomarkers that can enhance prognostic evaluations and support the development of more effective therapeutic strategies for LIHC.
View Article and Find Full Text PDFMetabolic reprogramming promotes cancer aggressiveness and an immune-suppressive tumor microenvironment. Loss of the Y chromosome (LOY) drives both phenotypes in bladder cancer (BC). We investigated the hypothesis that LOY leads to metabolic reprogramming using untargeted metabolomic profiling of human BC cells and analysis of pan-cancer transcriptomic datasets.
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