Systematic analysis of expression profiles of HMGB family members for prognostic application in non-small cell lung cancer

Background: Lung cancer is a significant challenge to human health. Members of the high mobility group (HMG) superfamily (HMGB proteins) are implicated in a wide variety of physiological and pathophysiological processes, but the expression and prognostic value of HMGB family members in non-small cell lung cancer (NSCLC) have not been elucidated. Methods: In this study, ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, starBase, OncomiR databases, and GeneMANIA were utilized to evaluate the prognostic significance of HMGB family members in NSCLC. Results: HMGB2/3 expression levels were higher in NSCLC patients. HMGB1 expression was higher in lung squamous cell carcinoma (LUSC) and was lower in lung adenocarcinoma (LUAD) tissue than in normal lung tissue. HMGB2 expression was related to cancer stage. Increased HMGB1 mRNA expression levels were associated with improved lung cancer prognosis, including overall survival (OS), first-progression survival (FP), and post-progression survival (PPS). There was no significant association between HMGB2 levels and prognostic indicators. HMGB3 expression was associated with poorer OS. GeneMANIA and GO/KEGG pathway analysis showed that HMGB family members mainly associated with chromosome condensation, regulation of chromatin organization, and nucleosome binding in NSCLC. HMGBs expression were closely correlated with infiltrating levels of specific types of immune cells in NSCLC, especially Th2 cells, Th17 cells, and mast cells. hsa-miR-25-3p, hsa-miR-374a-3p, and hsa-miR-93-5p were significantly positively correlated with HMGB1, HMGB2, and HMGB3, respectively. However, hsa-miR-30a-5p was predicted to significantly negatively regulate HMGB3 expression. Conclusion: Our study revealed that HMGB1 is positively related to the improved prognosis in NSCLC, and demonstrate that HMGB3 might be a risk factor for poorer survival of NSCLC patients.