AUTHOR=Lin Tong , Zhang Yingzhao , Lin Zhimei , Peng Lisheng 

TITLE=Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.764245

DOI=10.3389/fgene.2021.764245

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> High mobility group box (HMGB) proteins are DNA chaperones involved in transcription, DNA repair, and genome stability. Extracellular HMGBs also act as cytokines to promote inflammatory and immune responses. Accumulating evidence has suggested that HMGBs are implicated in cancer pathogenesis; however, their prognostic and immunological values in pan-cancer are not completely clear.</p><p><bold>Methods:</bold> Multiple tools were applied to analyze the expression, genetic alternations, and prognostic and clinicopathological relevance of HMGB in pan-cancer. Correlations between HMGB expression and tumor immune-infiltrating cells (TIICs), immune checkpoint (ICP) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) in pan-cancer were investigated to uncover their interactions with the tumor immune microenvironment (TIME). Gene set enrichment analysis (GSEA) was conducted for correlated genes of HMGBs to expound potential mechanisms.</p><p><bold>Results:</bold> HMGB expression was significantly elevated in various cancers. Both prognostic and clinicopathological significance was observed for <italic>HMGB1</italic> in ACC; <italic>HMGB2</italic> in ACC, LGG, LIHC, and SKCM; and <italic>HMGB3</italic> in ESCA. Prognostic values were also found for <italic>HMGB2</italic> in KIRP and MESO and <italic>HMGB3</italic> in BRCA, SARC, SKCM, OV, and LAML. The global alternation of HMGBs showed prognostic significance in ACC, KIRC, and UCEC. Furthermore, HMGBs were significantly correlated with TIIC infiltration, ICP expression, MSI, and TMB in various cancers, indicating their regulations on the TIME. Lastly, results of GSEA-illuminated genes positively correlated with HMGBs which were similarly chromosome components participating in DNA activity-associated events.</p><p><bold>Conclusion:</bold> This study demonstrated that HMGBs might be promising predictive biomarkers for the prognosis and immunotherapeutic response, also immunotherapy targets of multiple cancers.</p>