Hsa_circ_0072309 is a prognostic biomarker and is correlated with immune infiltration in gastric cancer

Bei-Bei Xu; Yi Huang; En-Dian Zheng; Jing-Ya Wang; Chen-Jing Zhang; Xiao-Ge Geng; Ya-Nan Wang; Wen-Sheng Pan

doi:10.1016/j.heliyon.2023.e13191

Hsa_circ_0072309 is a prognostic biomarker and is correlated with immune infiltration in gastric cancer

Heliyon. 2023 Feb 4;9(2):e13191. doi: 10.1016/j.heliyon.2023.e13191. eCollection 2023 Feb.

Authors

Bei-Bei Xu^{1

2

3}, Yi Huang⁴, En-Dian Zheng², Jing-Ya Wang³, Chen-Jing Zhang³, Xiao-Ge Geng³, Ya-Nan Wang⁵, Wen-Sheng Pan^{1

3

6}

Affiliations

¹ Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215000, China.
² Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, 325000, Zhejiang, China.
³ Department of Gastroenterology, Zhejiang Provincial People's Hospital, Hangzhou, 310000, Zhejiang, China.
⁴ Department of General Surgery, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou, 325000, Zhejiang, China.
⁵ Zhejiang University of Technology, Hangzhou, 310000, Zhejiang, China.
⁶ People's Hospital of Hangzhou Medical College, Hangzhou, 310000, Zhejiang, China.

Abstract

Background: Hsa_circ_0072309 has been identified as a tumor suppressor in several carcinomas. However, its precise role in gastric cancer (GC) remains largely unknown. This study was aimed to explore the precise role of Hsa_circ_0072309 in GC.

Methods: The transcriptional and clinical data of stomach adenocarcinoma were downloaded using the University of California SantaCruz (UCSC) Xena browser. The circular RNA (circRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database. The expression profile and survival analysis of differentially expressed micro RNAs (DEMIs) and differentially expressed messenger RNAs (DEMs) were performed. Correlations between the expression and immune infiltration of the DEMS were studied. Additionally, the expression of hsa_circ_0072309 in GC tissues and cell lines were validated, and the relationship between its expression and clinical features was investigated. Gain- and loss-of function experiments and molecular interaction experiments were also conducted.

Results: Overall, 7 differentially expressed circRNAs, 13 DEMIs, and 17 DEMs were screened. Two DEMIs (hsa_miR-34a-3p and hsa_miR-326) and five DEMs (C7, MARCKSL1, UBE2T, OLR1, and HOXC11) showed significant differences in the high- and low-risk groups. The most significantly enriched Gene Ontology terms were the circadian regulation of gene expression and protein binding. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were the PI3K-Akt and Ras signal pathways. Additionally, six genes were significantly correlated with immune infiltration. The real-time quantitative PCR (RT-qPCR) results revealed a significant downregulation of hsa_circ_0072309 in GC tissues related to tumor size, vascular invasion, and lymph node metastasis. A hsa_circ_0072309 overexpression suppressed whereas a hsa_circ_0072309 knockdown promoted GC cells proliferation and migration in vitro; in addition, hsa_circ_0072309 could directly bind to has-miR-34a-3p and has-miR-330-5p.

Conclusions: Hsa_circ_0072309 is a potential diagnostic biomarker for GC, and complement component 7 may be a tumor suppressor. These may potentially predict the prognosis of patients with GC and may become new therapeutic targets.

Keywords: Circular RNA; Complement component 7; Gastric cancer; Immune infiltration; Lymph node metastasis.