Luo Yuqi, Deng Xuesong, Liao Weihua, Huang Yiwen, Lu Caijie
Department of Gastrointestinal and Hepatobiliary Surgery, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong, China.
Department of Hepatobiliary Surgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
Front Genet. 2023 Mar 30;14:1109683. doi: 10.3389/fgene.2023.1109683. eCollection 2023.
Colorectal cancer (CRC) is the second most common cancer in China. Autophagy plays an important role in the initiation and development of CRC. Here, we assessed the prognostic value and potential functions of autophagy-related genes (ARGs) using integrated analysis using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) and RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA). We analyzed GEO-scRNA-seq data from GEO using various single-cell technologies, including cell clustering, and identification of differentially expressed genes (DEGs) in different cell types. Additionally, we performed gene set variation analysis (GSVA). The differentially expressed ARGs among different cell types and those between CRC and normal tissues were identified using TCGA-RNA-seq data, and the hub ARGs were screened. Finally, a prognostic model based on the hub ARGs was constructed and validated, and patients with CRC in TCGA datasets were divided into high- and low-risk groups based on their risk-score, and immune cells infiltration and drug sensitivity analyses between the two groups were performed. We obtained single-cell expression profiles of 16,270 cells, and clustered them into seven types of cells. GSVA revealed that the DEGs among the seven types of cells were enriched in many signaling pathways associated with cancer development. We screened 55 differentially expressed ARGs, and identified 11 hub ARGs. Our prognostic model revealed that the 11 hub ARGs including CTSB, ITGA6, and S100A8, had a good predictive ability. Moreover, the immune cell infiltrations in CRC tissues were different between the two groups, and the hub ARGs were significantly correlated with the enrichment of immune cell infiltration. The drug sensitivity analysis revealed that the patients in the two risk groups had difference in their response to anti-cancer drugs. We developed a novel prognostic 11-hub ARG risk model, and these hubs may act as potential therapeutic targets for CRC.
结直肠癌（CRC）是中国第二大常见癌症。自噬在CRC的发生和发展中起重要作用。在此，我们使用来自基因表达综合数据库（GEO）的单细胞RNA测序（scRNA-seq）数据和来自癌症基因组图谱（TCGA）的RNA测序（RNA-seq）数据进行综合分析，评估自噬相关基因（ARG）的预后价值和潜在功能。我们使用包括细胞聚类在内的各种单细胞技术分析来自GEO的GEO-scRNA-seq数据，并鉴定不同细胞类型中的差异表达基因（DEG）。此外，我们进行了基因集变异分析（GSVA）。使用TCGA-RNA-seq数据鉴定不同细胞类型之间以及CRC与正常组织之间差异表达的ARG，并筛选出核心ARG。最后，构建并验证了基于核心ARG的预后模型，根据风险评分将TCGA数据集中的CRC患者分为高风险组和低风险组，并对两组之间的免疫细胞浸润和药物敏感性进行了分析。我们获得了16270个细胞的单细胞表达谱，并将它们聚类为七种细胞类型。GSVA显示，七种细胞类型中的DEG在许多与癌症发展相关的信号通路中富集。我们筛选出55个差异表达的ARG，并鉴定出11个核心ARG。我们的预后模型显示，包括CTSB、ITGA6和S100A8在内的11个核心ARG具有良好的预测能力。此外，两组CRC组织中的免疫细胞浸润不同，核心ARG与免疫细胞浸润的富集显著相关。药物敏感性分析显示，两个风险组的患者对抗癌药物的反应存在差异。我们开发了一种新的11个核心ARG预后风险模型，这些核心可能作为CRC的潜在治疗靶点。
