Upregulated HMGB3 resulting in the poor prognosis of lung adenocarcinoma by activating stromal angiogenesis through immune microenvironment

Abstract

Abstract HMGB3 belongs to the high mobility group box (HMGB) family and the abnormally increased HMGB3 is associated with various types of malignancy progression. However, there is exiguous well clarified research to illustrate the correlation between HMGB3 and lung cancer. The expression profile data of lung adenocarcinoma (LUAD) were obtained from GEO and TCGA databases. The differential expression, prognostic survival, clinical characters, functional enrichment and immune infiltration were analyzed through R software, Kaplan–Meier (KM) plotter, ClusterProfiler package and ssGSEA algorithm. Besides, further research on HMGB3 expression level was confirmed using xenograft mice through immunohistochemistry and western blot assays. Results showed that HMGB3 was highly expressed in LUAD samples compared with adjacent normal samples. The T stage, pathologic stage, smoker and angiogenesis within the LUAD patients were positively correlated with HMGB3 expression. Functional enrichment analysis indicated that the correlative genes of HMGB3 are most related to the cell cycle process. HMGB3 is weakly related to the immune infiltration cells in LUAD stromal. However, increased existence of HMGB3 induced active angiogenesis in LUAD stromal and possibly accelerated the tumor progression through immune microenvironment. In conclusion, we confirmed that HMGB3 is a biomarker of poor prognosis for LUAD. The operative mechanism of which is activating tumor angiogenesis through immune infiltration cells. Further study will focus on exploring the related pathways in angiogenesis and immune microenvironment.