Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
PeerJ. 2023 Oct 16;11:e16243. doi: 10.7717/peerj.16243. eCollection 2023.
Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. However, the precise mechanisms and specific biomarkers of GC have not been fully elucidated. We therefore sought to identify and validate the genes associated with GC.
RNA sequencing was performed on gastric tissue specimens from 10 cases each of non-atrophic gastritis (NAG), intestinal metaplasia (IM), and GC. Validation of gene expression was conducted through immunohistochemistry (IHC) staining. The Kaplan-Meier Plotter database was utilized to screen genes associated with prognosis, while protein-protein interaction analysis was conducted to identify hub genes.
In GC-IM, the differentially expressed genes (DEGs) were predominantly enriched in pathways related to ECM-receptor interaction, focal adhesion, PI3K-Akt pathway, and pathways in cancer. Conversely, in IM-NAG, the DEGs were primarily enriched in pathways associated with fat digestion and absorption, pancreatic secretion, and retinol metabolism. IHC staining revealed elevated expression levels of KLK7 and KLK10 in GC. Specifically, KLK7 expression was found to be correlated with differentiation ( = 0.025) and depth of invasion ( = 0.007) in GC, while both KLK7 and KLK10 were associated with the overall survival ( < 0.05). Furthermore, a total of ten hub genes from DEGs in GC-NAG (COL6A2, COL1A1, COL4A1, COL1A2, SPARC, COL4A2, FN1, PCOLCE, SERPINH1, LAMB1) and five hub genes in IM-NAG (SI, DPP4, CLCA1, MEP1A, OLFM4) were demonstrated to have a significant correlation with the prognosis of GC.
The present study successfully identified and validated crucial genes associated with GC, providing valuable insights into the underlying mechanisms of this disease. The findings of this study have the potential to inform clinical practice.
胃癌（GC）是全球癌症相关死亡的第四大原因。然而，GC 的精确机制和特定生物标志物尚未完全阐明。因此，我们试图确定并验证与 GC 相关的基因。
对 10 例非萎缩性胃炎（NAG）、肠上皮化生（IM）和 GC 的胃组织标本进行 RNA 测序。通过免疫组织化学（IHC）染色验证基因表达。利用 Kaplan-Meier Plotter 数据库筛选与预后相关的基因，通过蛋白质-蛋白质相互作用分析识别枢纽基因。
在 GC-IM 中，差异表达基因（DEGs）主要富集在 ECM-受体相互作用、焦点粘连、PI3K-Akt 通路和癌症通路相关的途径中。相反，在 IM-NAG 中，DEGs 主要富集在与脂肪消化和吸收、胰腺分泌和视黄醇代谢相关的途径中。IHC 染色显示 GC 中 KLK7 和 KLK10 的表达水平升高。具体而言，KLK7 的表达与 GC 的分化（=0.025）和浸润深度（=0.007）相关，而 KLK7 和 KLK10 均与总生存期相关（<0.05）。此外，GC-NAG 中 DEGs 的十个枢纽基因（COL6A2、COL1A1、COL4A1、COL1A2、SPARC、COL4A2、FN1、PCOLCE、SERPINH1、LAMB1）和 IM-NAG 中的五个枢纽基因（SI、DPP4、CLCA1、MEP1A、OLFM4）与 GC 的预后显著相关。
本研究成功鉴定和验证了与 GC 相关的关键基因，为该疾病的潜在机制提供了有价值的见解。本研究的结果有可能为临床实践提供信息。
