Wang Guangwen, Wu Zhenhua, Huang Yesheng, Li Yingbang, Bai Yunpeng, Luo Zhidan, Huang Wendong, Chen Zanxiong
Center of Scientific Research, Maoming People's Hospital, Maoming, China.
Department of Gastroenterology, Maoming People's Hospital, Maoming, China.
J Gastrointest Oncol. 2022 Apr;13(2):593-604. doi: 10.21037/jgo-22-244.
In-depth research on tumors has shown that cancer stem cells (CSCs) play a crucial role in tumorigenesis. However, the mechanisms underlying the growth and maintenance of CSCs in stomach adenocarcinoma (STAD) are unclear. This study sought to investigate the expression of stem cell-related genes in STAD.
We identified key genes related to STAD stem cell characteristics by combining gene expression data obtained from The Cancer Genome Atlas to define a messenger ribonucleic acid expression-based stemness index (mRNAsi) based on mRNA expression. The correlations between the mRNAsi and STAD clinical characteristics, including age, tumor grade, pathological stage, and survival status, were explored. Additionally, a weighted gene co-expression network analysis was conducted to identify relevant modules and key genes. The expression verification and functional analysis of the key genes was carried out using multiple databases, including the TIMER (https://cistrome.shinyapps.io/timer/), and Gene Expression Profiling Integrative Analysis, and Gene Expression Omnibus databases.
The mRNAsi score was closely related to the clinical characteristics of STAD, including age, tumor grade, pathological stage, and survival status. Similarly, the mRNAsi score was significantly higher in STAD tissues than normal tissues, and the score decreased with tumor stage. The higher the mRNAsi score, the higher the overall survival rate. We screened a module of interest and found a strong correlation between 19 key genes. Among these 19 key genes, 16 had previously been shown to be closely related to STAD survival. The functional analysis showed that these key genes were linked to cell-cycle events, such as chromosome separation, mitosis, and microtubule movement.
We identified 19 key genes that play an important role in the maintenance of STAD stem cells. Among these genes, 16 play a role in predicting the prognosis of STAD patients. The cell-cycle pathway was the most important signaling pathway for the key genes associated with STAD stem cells. These findings may provide a new rationale for screening therapeutic targets and the characterization of STAD stem cells.
对肿瘤的深入研究表明，癌症干细胞（CSCs）在肿瘤发生中起关键作用。然而，胃腺癌（STAD）中癌症干细胞生长和维持的潜在机制尚不清楚。本研究旨在调查STAD中干细胞相关基因的表达。
我们通过结合从癌症基因组图谱获得的基因表达数据，确定与STAD干细胞特征相关的关键基因，以基于mRNA表达定义基于信使核糖核酸表达的干性指数（mRNAsi）。探讨了mRNAsi与STAD临床特征之间的相关性，包括年龄、肿瘤分级、病理分期和生存状态。此外，进行了加权基因共表达网络分析以识别相关模块和关键基因。使用多个数据库，包括TIMER（https://cistrome.shinyapps.io/timer/）、基因表达谱综合分析和基因表达综合数据库，对关键基因进行表达验证和功能分析。
mRNAsi评分与STAD的临床特征密切相关，包括年龄、肿瘤分级、病理分期和生存状态。同样，STAD组织中的mRNAsi评分显著高于正常组织，且评分随肿瘤分期降低。mRNAsi评分越高，总生存率越高。我们筛选了一个感兴趣的模块，发现19个关键基因之间存在强相关性。在这19个关键基因中，有16个先前已被证明与STAD生存密切相关。功能分析表明，这些关键基因与细胞周期事件相关，如染色体分离、有丝分裂和微管运动。
我们鉴定出19个在维持STAD干细胞中起重要作用的关键基因。在这些基因中，有16个在预测STAD患者预后中起作用。细胞周期途径是与STAD干细胞相关的关键基因最重要的信号通路。这些发现可能为筛选治疗靶点和STAD干细胞的表征提供新的理论依据。
