DISC1 as a prognostic biomarker correlated with immune infiltrates in gastric cancer

• Published in: Heliyon 2023-04, Vol.9 (4), p.e15058-e15058, Article e15058
• Main Authors: Zheng, Shiyao, Chen, Yongyuan, Yu, Shiya, Weng, Caiming, Lin, Nan, Luo, Ziqiang, Wang, Yuanzhao, Xiong, Ping, Teng, Zhun, Wang, Yu, Zhao, Hu, Xiao, Chunhong
• Format: Article
• Language: English
• Subjects: Bioinformatics; DISC1; Gastric cancer; Prognosis; Tumor infiltrating lymphocytes
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e15058

Multiple mental diseases could arise in people who have the disrupted in schizophrenia 1 (DISC1) gene. However, it was unknown how DISC1 might contribute to the development of tumors and immune responses. We extracted data from the Cancer Genome Atlas (TCGA) and TISIDB databases from stomach adenocarcinoma (STAD) patients, which revealed that DISC1 overexpression was closely associated with tumor histological type (mucinous vs. tubular, OR = 2.860, CI = 1.423–5.872, p = 0.004), as well as tumor stage and grade. Furthermore, the higher the DISC1 expression, the lower the overall 10-year survival rate. Patients with low DISC1 expression had a significantly longer progression-free interval (PFI) and disease-specific survival (DSS) than patients with high DISC1 expression. However, patients with higher DISC1 expression in the T3&T4, N0&N1 and M0 subgroups had poorer prognosis in terms of OS, DSS and PFI, as could be seen in the subgroup survival analysis. Public datasets were used to predict lncRNA-miRNA-DISC1 regulation. DISC1 was significantly up-regulated in GC(gastric cancer), and its expression levels showed a moderate to strong positive correlation with infiltration levels of effector memory T cells (Tem) and central memory T cells (Tcm), and a negative correlation was observed with Th17 cells and NK CD56bright cells. In addition, concomitant with the high expression of the DISC1 gene was a decrease in MHC-I (Major Histocompatibility Complex-I)expression and an increase in MHC-II expression, and altered chemokine expression. The upregulation of CXCL12 and CXCR4 expression could be caused by an increase in DISC1 expression. The above expression variability and correlation suggest a role for DISC1 in regulating tumor immunity in GC. These findings suggest that high expression of DISC1 could be an independent prognostic factor for GC.