利用机器学习识别胃癌肿瘤干性基因并开发预后模型

Guo-Xing Li, Yun-Peng Chen, You-Yang Hu, Wen-Jing Zhao, Yun-Yan Lu, Fu-Jian Wan, Zhi-Jun Wu, Xiang-Qian Wang, Qi-Ying Yu
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引用次数: 0

摘要

胃癌是一项艰巨的挑战,其特点是使人衰弱,预后往往很糟糕。新的证据强调,肿瘤干细胞在加剧胃癌耐药性和助长疾病复发方面起着关键作用。因此,鉴定导致肿瘤干细胞的基因至关重要。本研究采用了一种包含ssGSEA、WGCNA和各种机器学习算法的综合方法,致力于确定肿瘤干性关键基因(TSKGs)。随后,这些基因被用来构建预后模型,即肿瘤干性风险基因预后模型(TSRGPM)。通过 PCA、Cox 回归分析和 ROC 曲线分析,肿瘤干性风险评分(TSRS)在患者风险分层方面的功效得到了强调,肯定了其作为独立预后指标的能力。值得注意的是,TSRS 与胃癌淋巴结转移有显著相关性。此外,利用 CIBERSORT 等算法剖析免疫浸润模式,发现 TSRS 与单核细胞和其他细胞之间存在显著关联。随后对肿瘤干性风险基因(TSRGs)进行了仔细研究,最终确定了CDC25A,并对其进行了详细调查。生物信息学分析揭示了 CDC25A 在驱动肿瘤恶性表型方面的作用,它对胃癌的细胞增殖和 DNA 复制有明显的影响。值得注意的是,体外实验的验证证实了生物信息学的发现,阐明了 CDC25A 的表达在调节胃癌肿瘤干性中的关键作用。总之,已建立并通过验证的 TSRGPM 有望用于预后判断和潜在治疗目标的确定,从而预示着胃癌的个性化治疗将迈出关键的一步。
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Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer
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 in vitro 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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