LncRNA DIRC1 is a novel prognostic biomarker and correlated with immune infiltrates in stomach adenocarcinoma

The potential application value of Long non-coding RNA disrupted in renal carcinoma 1 (DIRC1) has not yet been explored, the purpose of this study was to explore the relationship between DIRC1 and stomach adenocarcinoma (STAD) based on the cancer genome atlas database. Wilcoxon rank sum test, Chi-square test, Fisher test and logistic regression were used to evaluate relationships between clinical-pathologic features and DIRC1 expression. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of DIRC1 using area under curve (AUC) score. Kaplan-Meier method was used to assess the impact of DIRC1 on prognosis and the impact of DIRC1-related hub genes on prognosis. Gene oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict the function of differentially expressed genes associated with DIRC1. Gene set enrichment analysis (GSEA) was used to predict biological states or processes associated with DIRC1. Immune infiltration analysis was performed to identify the significantly involved functions of DIRC1. Protein-protein interaction (PPI) networks were established and 10 hub genes identified with Cytoscape software. Real time-polymerase chain reaction (RT-PCR) was used to detect the expression of DIRC1 in Gastric Cancer patients and healthy people. Increased DIRC1 expression in STAD was associated with T stage (P = .004), race (P = .045), histologic grade (P = .029) and anatomic neoplasm subdivision (P = .034). ROC curve suggested the significant diagnostic ability of DIRC1 (AUC = 0.779). High DIRC1 expression predicted a poorer Overall survival (P = .004, hazard ratio: 1.63; 95% confidence interval: 1.17-2.27; P = .034). GO and KEGG analysis demonstrated that DIRC1 is related to epidermis, collagen-containing extracellular matrix, receptor-ligand activity, protein digestion and absorption, etc. GSEA demonstrated that E2F target, G2M checkpoint, Myc target, interferon gamma reaction were differentially enriched in the high DIRC1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between DIRC1 and macrophages, dendritic cells, and Th1 cells were the strongest. Coregulatory proteins were included in the PPI network, higher expressions of 4 hub genes were associated with worse prognosis in STAD. RT-PCR showed that the expression of DIRC1 in the serum of Gastric Cancer patients was higher than healthy people (P = .027). DIRC1 expression was significantly correlated with poor survival and immune infiltrations in STAD, and it may be a promising prognostic biomarker in STAD.

Automated summary

This study found that increased expression of DIRC1 in stomach adenocarcinoma (STAD) was associated with clinical-pathologic features such as T stage, race, histologic grade, and anatomic neoplasm subdivision, and high DIRC1 expression predicted poorer overall survival. Genes associated with DIRC1 were found to be related to functions such as epidermis, collagen-containing extracellular matrix, receptor-ligand activity, and protein digestion and absorption. Immune infiltration analysis revealed a strong correlation between DIRC1 and immune cells like macrophages.