Li Fazhan, Wen Huijuan, Bukhari Ihtisham, Liu Bin, Guo Chenxu, Ren FeiFei, Tang Youcai, Mi Yang, Zheng Pengyuan
Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
Front Genet. 2022 Jun 8;13:869967. doi: 10.3389/fgene.2022.869967. eCollection 2022.
Gastric cancer (GC) is a highly fatal and common malignancy of the digestive system. Recent therapeutic advancements have significantly improved the clinical outcomes in GC, but due to the unavailability of suitable molecular targets, a large number of patients do not respond to the immune checkpoint inhibitors (ICI) therapy. To identify and validate potential therapeutic and prognostic targets of gastric cancer, we used the "inferCNV" R package for analyzing single-cell sequencing data (GSE112302) of GC and normal epithelial cells. First, by using LASSO, we screened genes that were highly correlated with copy number variations (CNVs). Therefrom, five gene signature (, , , , and ) was selected by cross-validating the prognosis and risk management with the GC RNA-seq data obtained from GEO and TCGA. Moreover, the correlation analyses between CNVs of these genes and immune cell infiltration in gastric cancer identified as a potential prognostic marker. Finally, showed high expression in gastric cancer samples and cell lines, then siRNA-mediated silencing of expression in gastric cancer cells showed significant proliferation arrest in MGC803 cells. Here, we conclude that CNVs are key regulators of the immune cells infiltration in gastric TME as well as cancer development, and could potentially be used as a prognostic and therapeutic marker in gastric cancer.
胃癌（GC）是消化系统一种高度致命且常见的恶性肿瘤。近期的治疗进展显著改善了胃癌的临床结局，但由于缺乏合适的分子靶点，大量患者对免疫检查点抑制剂（ICI）治疗无反应。为了鉴定和验证胃癌潜在的治疗和预后靶点，我们使用“inferCNV”R包分析胃癌和正常上皮细胞的单细胞测序数据（GSE112302）。首先，通过使用套索回归，我们筛选出与拷贝数变异（CNV）高度相关的基因。据此，通过对从GEO和TCGA获得的胃癌RNA测序数据进行预后和风险管理交叉验证，选择了五个基因特征（、、、和）。此外，这些基因的CNV与胃癌中免疫细胞浸润之间的相关性分析确定为潜在的预后标志物。最后，在胃癌样本和细胞系中高表达，然后通过siRNA介导沉默胃癌细胞中的表达显示MGC803细胞出现显著的增殖停滞。在此，我们得出结论，CNV是胃癌肿瘤微环境中免疫细胞浸润以及癌症发展的关键调节因子，并且可能用作胃癌的预后和治疗标志物。
