目的:全面研究影响IV期胃癌预后的临床病理危险因素。然而,在基因组和转录水平上影响IV期胃癌预后的因素尚未明确。
方法:突变和转录数据,连同人口统计,从TCGA数据库下载了44例IV期胃癌患者的临床病理和预后信息.进行单因素和多因素分析以确定重要的危险因素,并建立Nomogram模型来预测患者的预后。
结果:TTN,TP53,FLG,LRP1B,SYNE1和ARID1A是没有热点突变的最高突变基因之一。AHNAK2、ASCC3、DNAH3、DOP1A、MYLK,SIPA1L1,SORBS2,SYNE1和ANF462显着分层患者的预后。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。对突变和转录的富集分析揭示了细胞骨架和膜功能,细胞外基质功能,HPV感染,和几种癌症相关的通路是主要的异常。单变量分析揭示了一系列对患者预后进行分层的重要因素,主要包括癌症的位置,几个突变的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,和癌症位置作为独立的危险因素。已经建立了具有这些重要风险因素的列线图模型来预测患者预后。需要进一步验证以确保模型在实际临床实践中的有效性。
结论:癌症位置,SYNE1和DNAH3的突变状态以及COMMD3的转录水平是IV期胃癌的独立危险因素。利用这些因素建立Nomogram模型进行预后预测。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.