Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
The First Affiliated Hospital of Nanchang University, Nanchang, China.
Comput Biol Med. 2023 Sep;163:107227. doi: 10.1016/j.compbiomed.2023.107227. Epub 2023 Jul 3.
Gastric carcinoma (GC) is the fourth leading cause of cancer-related mortality worldwide. Patients with advanced GC tend to have poor prognoses and shortened survival. Finding novel predictive biomarkers for GC prognosis is an urgent need. Mitophagy is the selection degradation of damaged mitochondria to maintain cellular homeostasis, which has been shown to play both pro- and anti-tumor effects. This study combined single-cell sequencing data and transcriptomics to screen mitophagy-related genes (MRGs) associated with GC progression and analyze their clinical values. Reverse transcription-quantitative PCR (RT-qPCR) and immunochemistry (IHC) further verified gene expression profiles. A total of 18 DE-MRGs were identified after taking an intersection of single-cell sequencing data and MRGs. Cells with a higher MRG score were mainly distributed in the epithelial cell cluster. Cell-to-cell communications among epithelial cells with other cell types were significantly upregulated. We established and validated a reliable nomogram model based on DE-MRGs (GABARAPL2 and CDC37) and traditional clinicopathological parameters. GABARAPL2 and CDC37 displayed different immune infiltration states. Given the significant correlation between hub genes and immune checkpoints, targeting MRGs in GC may supplement more benefits to patients who received immunotherapy. In conclusion, GABARAPL2 and CDC37 may be prognostic biomarkers and candidate therapeutic targets of GC.
胃癌（GC）是全球导致癌症相关死亡的第四大原因。晚期 GC 患者往往预后较差，生存期较短。寻找新的 GC 预后预测生物标志物是当务之急。自噬是一种选择性降解受损线粒体以维持细胞内稳态的过程，它已被证明具有促进和抗肿瘤作用。本研究结合单细胞测序数据和转录组学筛选与 GC 进展相关的自噬相关基因（MRGs），并分析其临床价值。逆转录定量 PCR（RT-qPCR）和免疫化学（IHC）进一步验证了基因表达谱。通过对单细胞测序数据和 MRGs 进行交集处理，共鉴定出 18 个差异表达的 MRGs。具有更高 MRG 评分的细胞主要分布在上皮细胞簇中。上皮细胞与其他细胞类型之间的细胞间通讯明显上调。我们基于 DE-MRGs（GABARAPL2 和 CDC37）和传统临床病理参数建立并验证了一个可靠的列线图模型。GABARAPL2 和 CDC37 显示出不同的免疫浸润状态。鉴于核心基因与免疫检查点之间存在显著相关性，针对 GC 中的 MRGs 可能会为接受免疫治疗的患者带来更多益处。总之，GABARAPL2 和 CDC37 可能是 GC 的预后生物标志物和候选治疗靶点。
