Expression, tumor immune infiltration, and prognostic impact of HMGs in gastric cancer

Zhiheng Wu; Yang Huang; Weiwei Yuan; Xiong Wu; Hui Shi; Ming Lu; Aman Xu

doi:10.3389/fonc.2022.1056917

Expression, tumor immune infiltration, and prognostic impact of HMGs in gastric cancer

Front Oncol. 2022 Dec 7:12:1056917. doi: 10.3389/fonc.2022.1056917. eCollection 2022.

Authors

Zhiheng Wu^{1

2}, Yang Huang^{1

2}, Weiwei Yuan^{1

2}, Xiong Wu³, Hui Shi⁴, Ming Lu⁴, Aman Xu^{1

2}

Affiliations

¹ Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
² Department of General Surgery, Anhui Public Health Clinical Center, Hefei, Anhui, China.
³ School of Optometry and Ophthalmology and the Eye Hospital, Wenzhou Medical University, PR China, State Key Laboratory of Optometry, Ophthalmology, and Visual Science, Wenzhou, Zhejiang, China.
⁴ Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.

Abstract

Background: In the past decade, considerable research efforts on gastric cancer (GC) have been expended, however, little advancement has been made owing to the lack of effective biomarkers and treatment options. Herein, we aimed to examine the levels of expression, mutations, and clinical relevance of HMGs in GC to provide sufficient scientific evidence for clinical decision-making and risk management.

Methods: GC samples were obtained from The Cancer Genome Atlas (TCGA). University of California Santa Cruz (UCSC) XENA, Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, LinkedOmics, and DAVID databases were employed. The "ggplot2" package in the R software (×64 3.6.3) was used to thoroughly analyze the effects of HMGs. qRT-PCR was performed to assess HMG levels in GC cell lines.

Results: A total of 375 GC tissues and 32 paraneoplastic tissues were analyzed. The levels of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN1, HMGN2, and HMGN4 expression were increased in GC tissues relative to normal gastric tissues. HMGA1, HMGA2, HMGB1, HMGB2, and HMGB3 were highly expressed in GC cell lines. The OS was significantly different in the group showing low expressions of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN2, HMGN3, and HMGN5. There was a significant difference in RFS between the groups with low HMGA2, HMGB3, and high HMGN2 expression. The levels of HMGA2, HMGB3, and HMGN1 had a higher accuracy for prediction to distinguish GC from normal tissues (AUC value > 0.9). HMGs were tightly associated with immune infiltration and tumor immune escape and antitumor immunity most likely participates in HMG-mediated oncogenesis in GC. GO and KEGG enrichment analyses showed that HMGs played a vital role in the cell cycle pathway.

Conclusions: Our results strongly suggest a vital role of HMGs in GC. HMGA2 and HMGB3 could be potential markers for prognostic prediction and treatment targets for GC by interrupting the cell cycle pathway. Our findings might provide renewed perspectives for the selection of prognostic biomarkers among HMGs in GC and may contribute to the determination of the optimal strategy for the treatment of these patients.

Keywords: Expression; HMGs; Prognostic biomarkers; TCGA; gastric cancer.