Zheng Shiyao, Chen Yongyuan, Yu Shiya, Weng Caiming, Lin Nan, Luo Ziqiang, Wang Yuanzhao, Xiong Ping, Teng Zhun, Wang Yu, Zhao Hu, Xiao Chunhong
Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350025, Fujian, PR China.
College of Clinical Medicine for Oncology, Fujian Medical University, Fuzhou, Fujian, 350004, Fujian, PR China.
Heliyon. 2023 Mar 29;9(4):e15058. doi: 10.1016/j.heliyon.2023.e15058. eCollection 2023 Apr.
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.
精神分裂症1(DISC1)基因发生突变的人群可能会患上多种精神疾病。然而,DISC1如何促进肿瘤发生和免疫反应尚不清楚。我们从癌症基因组图谱(TCGA)和TISIDB数据库中提取了胃腺癌(STAD)患者的数据,结果显示DISC1过表达与肿瘤组织学类型(黏液性与管状,OR = 2.860,CI = 1.423 - 5.872,p = 0.004)以及肿瘤分期和分级密切相关。此外,DISC1表达越高,总体10年生存率越低。DISC1低表达的患者比DISC1高表达的患者无进展生存期(PFI)和疾病特异性生存期(DSS)显著更长。然而,在T3&T4、N0&N1和M0亚组中,DISC1表达较高的患者在总生存期(OS)、DSS和PFI方面预后较差,亚组生存分析可见此情况。利用公共数据集预测lncRNA - miRNA - DISC1调控。DISC1在胃癌(GC)中显著上调,其表达水平与效应记忆T细胞(Tem)和中枢记忆T细胞(Tcm)的浸润水平呈中度至强正相关,与Th17细胞和NK CD56bright细胞呈负相关。此外,伴随DISC1基因的高表达,主要组织相容性复合体I(MHC - I)表达降低,MHC - II表达增加,趋化因子表达改变。DISC1表达增加可能导致CXCL12和CXCR4表达上调。上述表达变异性和相关性表明DISC1在GC肿瘤免疫调节中发挥作用。这些发现表明DISC1高表达可能是GC的一个独立预后因素。