A pan-cancer analysis of the oncogenic function of HMGB1 in human tumors

Sep 21, 2026

Although high mobility group box protein 1 (HMGB1) has been linked to cancer, a comprehensive pan-cancer characterization of its role remains limited. This study used TCGA and GEO to compare HMGB1 expression and relate it to survival across tumor types, then applied cBioPortal for HMGB1 alterations and quantified immune-cell infiltration. In 95 solid-tumor patients, HMGB1 somatic mutations were profiled by panel sequencing, highlighting prognostic and biological associations. Results show tumor-stage HMGB1 upregulation, survival links in specific cancers, and pathway involvement.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Cancer overview and need for pan-cancer studies

HMGB1 functions and relevance to tumors

Study databases and analytical strategy

Methods

TCGA and GEO expression analyses

cBioPortal genetic alteration and immune infiltration assessment

Clinical cohort sequencing and somatic mutation analysis

Results

HMGB1 expression across tumor types

Associations with overall and progression outcomes

HMGB1 alterations and cancer-specific prognosis

Immune infiltration links and CAF association

Co-expression and pathway enrichment

Conclusion

Biochemistry and Biophysics Reports 40 (2024) 101851 Contents lists available at ScienceDirect Biochemistry and Biophysics Reports journal [homepage:](homepage: www.elsevier.com/locate/bbrep)[ www.elsevier.com/locate/bbrep](homepage: www.elsevier.com/locate/bbrep) | A pan-cancer analysis of the oncogenic function of HMGB1 inhuman tumors
Hui-min Yanga,1, Xiang-ning Zhao b,1, Xiao-ling Li c, Xi Wang c, Yu Puc, Dong-kai Wei c, Zhe Li d,*
a Shanghai Singlera Medical Laboratory, 1rst Floor, No. 20 Building, 500 Furonghua Road, Pudong New District, Shanghai, China b Department of Surgical Oncology, Shanghai Mengchao Cancer Hospital, 118 Qianyang Road, Jiading District, Shanghai, China c Suzhou Func Biotech Inc, Suzhou, Jiangsu, China
d Department of Breast Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New District, Shanghai, China | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords: Cancer HMGB1
Mutation Prognostic
Immune cell infiltration | | Background: Although high mobility group box protein 1 (HMGB1) has been researched in relation to cancer in many investigations, a thorough investigation of its role in pan-cancer has yet to be conducted. With the objective of bridging this gap, we delved into the functions of HMGB1 in various tumors.
Methods: This investigation employed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to examine HMGB1 gene expression differences and correlation with survival across various human tumors. Then, genetic alterations of HMGB1 were analyzed by tool cBioPortal, and immune cell infiltration was assessed. Finally, we gathered clinial samples from 95 patients with various types of solid tumor and performed somatic mutation analysis using panel sequencing. This further highlighted the role of HMGB1 in different solid tumors.
Results: There was a notable elevation of HMGB1 gene expression in tumor tissues as opposed to non-cancerous tissues across the bulk of tumor types. Elevated HMGB1 gene expression had a connection with shorter overall survival, progression-free survival, and disease-free survival in specific tumor types. Genetic alterations of HMGB1 suggested that the amplifications and mutations of HMGB1 may impact the prognosis of breast cancer (BRCA) and liver hepatocellular carcinoma (LIHC). Both BRCA and mesothelioma (MESO) displayed a connection between the infiltration of cancer-associated fibroblasts (CAFs) and HMGB1 gene expression. Moreover, HMGB1 co-expression analysis revealed its association with genes involved in RNA splicing, mRNA processing, and modulation of mRNA metabolic processes. Additionally, a pathway analysis by use of the Kyoto Encyclopedia of Genes and Genomes (KEGG) unveiled that HMGB1 was implicated in the pathogenic mechanisms of"Hepatitis B," "Viral Carcinogenesis," and "Hepatocellular Carcinoma." Based on somatic mutation analysis of 95 patients with different solid tumors, we found that the frequency of HMGB1 mutations was higher in Liver cancer patients compared to other solid tumors. This finding is consistent with our in-silico study results. Additionally, we discovered that the frequency of HMGB1 mutations ranked among the top 20 mutated genes in the 95 patients’ data, indicating that HMGB1 plays an important role in the development and prognosis of various solid tumors.
Conclusion: This pan-cancer study of HMGB1 underscores its potential as a signature marker and target for the management of various tumor types. | 1. Introduction Cancer is a complex disease marked by abnormal cell growth. Treating it is challenging due to its diverse nature, resistance to conventional therapies, and the heavy burden of side effects on patients. However, new strategies like personalized medicine, immunotherapy, * Corresponding author. E-mail address: [lizhezsh@126.com](lizhezsh@126.com) (Z. Li). 1 Hui-min

FAQs

What were the main findings about HMGB1 in tumors?

HMGB1 expression was elevated in tumor tissues compared with non-cancerous tissues across many tumor types. Higher HMGB1 expression correlated with worse survival in specific cancers, HMGB1 alterations related to prognosis in breast cancer and liver hepatocellular carcinoma, and HMGB1 mutations were more frequent in liver cancer patients, ranking among the top mutated genes in the cohort.

Sep 21, 2026

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