Upregulation of ZHX2 predicts poor prognosis and is correlated with immune infiltration in gastric cancer

• Published in: FEBS open bio Vol. 11; no. 6; pp. 1785 - 1798
• Main Authors: Cheng, Anqi, Guo, Xiong, Dai, Xinglong, Wang, Ziwei
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2021; John Wiley and Sons Inc; Wiley
• Subjects: Apoptosis; Cancer therapies; CD4 antigen; Cell proliferation; Chemotherapy; Cloning; Dendritic cells; Flow cytometry; Gastric cancer; Gene expression; Gene set enrichment analysis; Genomes; Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - immunology; Humans; immune infiltration; Infiltration; Leukocyte migration; Lymphocytes B; Lymphocytes T; Macrophages; Medical prognosis; Membranes; Metastases; Patients; Prognosis; Protein expression; Proteins; Stomach Neoplasms - diagnosis; Stomach Neoplasms - immunology; Transcription; Transcription Factors - genetics; Transcription Factors - immunology; Tumor Cells, Cultured; Up-regulation; Up-Regulation - immunology; Wound healing; ZHX2; Zinc finger proteins; United States > US; China; ZHX2; gastric cancer; immune infiltration; prognosis
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13160

The transcriptional repressor zinc finger homeobox 2 (ZHX2) is reported to regulate tumor progression in several human cancers, although little is known about its role in gastric cancer (GC). In the present study, we investigated the expression of ZHX2 and its relationship with the clinicopathological characteristics and prognosis of GC patients, and we also examined the effect of ZHX2 overexpression in GC cell lines. We used UALCAN (http://ualcan.path.uab.edu) and the Tumor Immune Estimation Resource (http://cistrome.org/TIMER) to examine ZHX2 mRNA expression, and also used Kaplan–Meier Plotter (https://kmplot.com) to determine whether ZHX2 expression was related to GC prognosis. Expression of ZHX2 protein was detected using immunohistochemical staining assays. Cell proliferation was evaluated using a cell counting kit‐8 and colony formation assays, whereas apoptosis was examined by flow cytometry. Wound healing and transwell assays were used to detect cell migration and invasion. We also performed Gene Set Enrichment Analysis (https://www.gsea‐msigdb.org) and used The Cancer Genome Atlas database (https://www.genome.gov/Funded‐Programs‐Projects/Cancer‐Genome‐Atlas) to examine the correlation of ZHX2 with immune infiltration. We report that ZHX2 is highly expressed in GC tissues and is significantly associated with clinical characteristics. Upregulation of ZHX2 predicted poor prognosis in GC. Furthermore, ZHX2 overexpression can promote the proliferation, invasion and migration, but inhibit apoptosis, of GC cells. High expression of ZHX2 in GC is correlated with the presence of infiltrating immune cells, including B cells, CD4+ T cells, macrophages and dendritic cells. Our data suggest that high expression of ZHX2 in GC predicts poor prognosis. In addition, ZHX2 may promote malignant behaviors of GC cells, and immune infiltration might be related to the oncogenic role of ZHX2 in GC. ZHX2 is upregulated in gastric cancer tissues at both the mRNA and protein level as validated by bioinformatic analysis and immunohistochemistry; moreover, its expression is correlated with the prognosis of gastric cancer patients. Upregulation of ZHX2 may promote malignance of gastric cancer cells. Furthermore, immune infiltration might underlie the oncogenic role of ZHX2 in gastric cancer.