Bioinformatic analysis of the prognostic value of ZNF860 in recurrence-free survival and its potential regulative network in gastric cancer

H.-X. Pan, H.-S. Bai, Y. Guo, Z.-Y. Cheng

Department of Oncology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. 49063656@qq.com

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• Oncology

OBJECTIVE: In this study, we aimed to investigate the expression profile of C2H2 zinc finger (ZNF) 860 (ZNF860) in gastric cancer (GC), its prognostic significance and its potential regulatory network in GC.

PATIENTS AND METHODS: The level-3 data in the Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) was acquired for a secondary analysis, in which clinicopathological, genetic and survival data from 415 GC patients were collected.

RESULTS: The gastric cancerous tissues had significantly upregulated ZNF860 expression. In univariate analysis, male patients, no responses to primary therapy, with male patients and high ZNF860 RNA expression were associated with unfavorable RFS in early GC (stage I/II). Multivariate analysis showed that high ZNF860 RNA expression was independently associated with shorter recurrence-free survival (RFS) in patients with early GC (HR: 5.289, 95%CI: 1.839-15.214, p=0.002). Among 413 cases of GC tumors with copy number alteration (CNA) data available, 35 cases (8.5%) had DNA amplification (+1/+2), while 121 cases (29.3%) had DNA copy loss. ZNF860 amplification was associated with significantly elevated ZNF860 expression. In comparison, DNA copy loss did not necessarily result in ZNF860 downregulation. The methylation of 5 CpG sites in ZNF860 gene (cg24264962, cg24391989, cg10702818, cg15840985, and cg25692785) was negatively correlated with ZNF860 expression. Six genes (OSBPL10, FAM208A, TOPBP1, SPTY2D1, NAB1, and CMTM6) were positively co-expressed with ZNF860, suggesting that ZNF860 probably acts as a transcription enhancer in GC.

CONCLUSIONS: ZNF860 RNA upregulation was an independent prognostic indicator in terms of RFS in stage I/II GC. DNA CNAs and methylation alterations might collaboratively regulate ZNF860 expression.