Integrated machine learning developed a prognosis-related gene signature to predict prognosis in oesophageal squamous cell carcinoma

Peng Tang, Baihui Li, Zijing Zhou, Haitong Wang, Mingquan Ma, Lei Gong, Yufeng Qiao, Peng Ren, Hongdian Zhang
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Abstract

The mortality rate of oesophageal squamous cell carcinoma (ESCC) remains high, and conventional TNM systems cannot accurately predict its prognosis, thus necessitating a predictive model. In this study, a 17-gene prognosis-related gene signature (PRS) predictive model was constructed using the random survival forest algorithm as the optimal algorithm among 99 machine-learning algorithm combinations based on data from 260 patients obtained from TCGA and GEO. The PRS model consistently outperformed other clinicopathological features and previously published signatures with superior prognostic accuracy, as evidenced by the receiver operating characteristic curve, C-index and decision curve analysis in both training and validation cohorts. In the Cox regression analysis, PRS score was an independent adverse prognostic factor. The 17 genes of PRS were predominantly expressed in malignant cells by single-cell RNA-seq analysis via the TISCH2 database. They were involved in immunological and metabolic pathways according to GSEA and GSVA. The high-risk group exhibited increased immune cell infiltration based on seven immunological algorithms, accompanied by a complex immune function status and elevated immune factor expression. Overall, the PRS model can serve as an excellent tool for overall survival prediction in ESCC and may facilitate individualized treatment strategies and predction of immunotherapy for patients with ESCC.

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综合机器学习开发出预测食管鳞状细胞癌预后的预后相关基因特征。
食管鳞状细胞癌(ESCC)的死亡率居高不下,传统的TNM系统无法准确预测其预后,因此需要一种预测模型。本研究基于从TCGA和GEO获得的260名患者的数据,使用随机生存森林算法构建了17个基因的预后相关基因特征(PRS)预测模型,并将其作为99种机器学习算法组合中的最优算法。从训练队列和验证队列的接收者操作特征曲线、C指数和决策曲线分析来看,PRS模型的预后准确性始终优于其他临床病理特征和以前发表的特征。在 Cox 回归分析中,PRS 评分是一个独立的不良预后因素。通过TISCH2数据库进行单细胞RNA-seq分析,PRS的17个基因在恶性细胞中主要表达。根据GSEA和GSVA,这些基因涉及免疫和代谢通路。根据七种免疫学算法,高风险组的免疫细胞浸润增加,同时伴有复杂的免疫功能状态和免疫因子表达升高。总之,PRS模型可作为预测ESCC总生存率的绝佳工具,有助于ESCC患者的个体化治疗策略和免疫疗法的预测。
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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