Mutational and transcriptional profile predicts the prognosis of stage IV gastric cancer – Prognostic factors for metastatic gastric cancer

IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Arab Journal of Gastroenterology Pub Date : 2024-08-01 DOI:10.1016/j.ajg.2024.05.001
Zhengyong Xie , Wenzhen Zhao , Yongzhong He , Yongli Ke , Zehang Li , Xuhui Zhang
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Abstract

Background and study aims

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.

Patients and 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.

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突变和转录谱预测 IV 期胃癌的预后 - 转移性胃癌的预后因素。
背景和研究目的:IV期胃癌预后的临床病理风险因素已得到全面研究。然而,IV 期胃癌预后在基因组和转录水平上的影响因素尚未得到很好的界定:从TCGA数据库下载了44例IV期胃癌患者的基因突变和转录数据,以及人口统计学、临床病理学和预后信息。进行单变量和多变量分析以确定重要的风险因素,并建立了预测患者预后的Nomogram模型:结果:TTN、TP53、FLG、LRP1B、SYNE1和ARID1A是突变率最高的基因,但没有热点突变。AHNAK2、ASCC3、DNAH3、DOP1A、MYLK、SIPA1L1、SORBS2、SYNE1和ANF462的突变状态显著影响了患者的预后。AQP10、HOXC8/9/10、COL10A1/COL11A1、WNT7B、KRT17和KLK6等多个基因的转录出现了明显的上调或下调。突变和转录的富集分析表明,细胞骨架和膜功能、细胞外基质功能、HPV 感染和一些癌症相关通路是主要的异常点。单变量分析显示了一系列重要的患者预后分层因素,主要包括癌症位置、多个突变基因和多个上调或下调基因。但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风险因素。利用这些重要的风险因素建立的 Nomogram 模型可以预测患者的预后。为确保该模型在实际临床实践中的有效性,还需要进一步验证: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。利用这些因素建立的Nomogram模型可用于预后预测。
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来源期刊
Arab Journal of Gastroenterology
Arab Journal of Gastroenterology Medicine-Gastroenterology
CiteScore
2.70
自引率
0.00%
发文量
52
期刊介绍: Arab Journal of Gastroenterology (AJG) publishes different studies related to the digestive system. It aims to be the foremost scientific peer reviewed journal encompassing diverse studies related to the digestive system and its disorders, and serving the Pan-Arab and wider community working on gastrointestinal disorders.
期刊最新文献
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