Background: Gastric cancer peritoneal metastasis has high mortality. At present, there is no effective way to cure the patients diagnosed with gastric cancer peritoneal metastasis due to its indistinct molecular mechanism. Therefore, to understand the pathogenesis and help for further target therapy, we conduct comprehensive analysis of peritoneal metastasis by bioinformatics in gastric cancer.
Methods: Microarray sequencing was used to find differential mRNAs and long non-coding RNAs (lncRNAs) expression between primary foci and peritoneal metastases lesion in gastric cancer. RT-qPCR was used to verify the expression levels of lncRNAs in gastric cancer cells after co-culture with adipocytes. TCGA, Cytoscape, lnCAR, cBioPoratal and R packages (ggrisk, survival, survminer, timeROC, forestplot, immunedeconv, ggplot2, pheatmap and ggpubr) were applied in this work.
Results: Adipocytes co-culture model was used to mimic the peritoneal microenvironment and found that LINC01151 (NR_126348), FAM27B (NR_027422) and LINC00924 (NR_027133) were up-regulated in co-culture group. Increased LINC00924 expression was significantly associated with reduced overall survival and up-regulated percentage abundance of tumor-infiltrating CD8⁺ T, B, macrophage and NK immune cells; moreover, immune checkpoint blockers (ICBs) had a worse effect on the LINC00924 high expression group. Furthermore, through univariate and multivariate Cox regression analysis, we found that LINC00924-related PEX5L in CNC network was an independent prognostic factor in gastric cancer progression.
Conclusion: LINC00924 expression was associated with poor survival, immune infiltrations and worse response to ICBs. LINC00924 might be immunotherapeutic targets of advanced gastric cancer.
Keywords: gastric cancer, LINC00924, immune infiltrations, target therapy