General Surgery Department, General Hospital of Southern Theatre Command, PLA, No.111 Liuhua Road, Yuexiu District, Guangzhou 510010, Guangdong Province, China.
Department of 2nd Oncology, Guangdong Second Provincial General Hospital, Guangzhou 510317, Guangdong Province, China.
Arab J Gastroenterol. 2024 Aug;25(3):275-283. doi: 10.1016/j.ajg.2024.05.001. Epub 2024 Jul 22.
The clinicopathological risk factors in the prognosis of stage IV gastric cancer have been comprehensively studied. However, the influencing factors of stage IV gastric cancer prognosis at genomic and transcriptional levels have not been well defined.
The mutational and transcriptional data, along with demographic, clinicopathological and prognostic information of 44 stage IV gastric cancer patients were downloaded from the TCGA database. Univariate and multivariate analyses were performed to identify the significant risk factors and a Nomogram model was established to predict the patient prognosis.
TTN, TP53, FLG, LRP1B, SYNE1 and ARID1A were among the top mutated genes without hot-spot mutations. The mutational status of AHNAK2, ASCC3, DNAH3, DOP1A, MYLK, SIPA1L1, SORBS2, SYNE1 and ANF462 significantly stratified the patient prognosis. The transcription of several genes, such as AQP10, HOXC8/9/10, COL10A1/COL11A1, WNT7B, KRT17 and KLK6 was significantly up-regulated or down-regulated. Enrichment analysis on mutations and transcription revealed cell skeleton and membrane function, extracellular matrix function, HPV infection, and several cancer-related pathways as the main aberrancies. Univariate analyses revealed a series of significant factors stratifying patient prognosis, mainly including cancer location, several mutated genes and many up- or down-regulated genes. However, subsequent multivariate analysis revealed SYNE1 mutation, DNAH3 mutation, COMMD3 transcription level, and cancer location as the independent risk factors. A Nomogram model has been established with these significant risk factors to predict the patient prognosis. Further validation is needed to ensure the effectiveness of the model in real clinical practice.
Cancer location, along with the mutational status of SYNE1 and DNAH3 and the transcriptional level of COMMD3 were independent risk factors of stage IV gastric cancer. A Nomogram model was established with these factors for prognosis prediction.
已经全面研究了 IV 期胃癌预后的临床病理危险因素。然而，IV 期胃癌在基因组和转录水平上的预后影响因素尚未得到很好的定义。
从 TCGA 数据库中下载了 44 名 IV 期胃癌患者的突变和转录数据，以及人口统计学、临床病理和预后信息。进行单变量和多变量分析以确定显著的风险因素，并建立列线图模型来预测患者的预后。
TTN、TP53、FLG、LRP1B、SYNE1 和 ARID1A 是突变频率较高但无热点突变的基因。AHNAK2、ASCC3、DNAH3、DOP1A、MYLK、SIPA1L1、SORBS2、SYNE1 和 ANF462 的突变状态显著分层了患者的预后。几个基因的转录，如 AQP10、HOXC8/9/10、COL10A1/COL11A1、WNT7B、KRT17 和 KLK6 显著上调或下调。突变和转录的富集分析显示，细胞骨架和膜功能、细胞外基质功能、HPV 感染和几个癌症相关途径是主要异常。单变量分析揭示了一系列显著的分层患者预后的因素，主要包括癌症位置、几个突变基因和许多上调或下调的基因。然而，随后的多变量分析显示 SYNE1 突变、DNAH3 突变、COMMD3 转录水平和癌症位置是独立的危险因素。该模型已经建立了这些显著的风险因素来预测患者的预后。需要进一步验证以确保模型在实际临床实践中的有效性。
癌症位置，以及 SYNE1 和 DNAH3 的突变状态和 COMMD3 的转录水平是 IV 期胃癌的独立危险因素。该模型已经建立了这些因素来预测预后。
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