The Comprehensive Role of High Mobility Group Box 1 (HMGB1) Protein in Different Tumors: A Pan-Cancer Analysis

Feb 1, 2023·
Hui Guan
,
Ming Zhong
,
Kongyang Ma
,
Chun Tang
,
Xiaohua Wang
Muzi Ouyang (Mia)
Muzi Ouyang (Mia)
,
Rencai Qin
,
Jiasi Chen
,
Enyi Zhu
,
Ting Zhu
,
Yongping Lu
,
Yu Liu
,
Chengzi Tian
,
Zhihua Zheng
· 0 min read
DOI
Abstract
HMGB1 is a highly conserved nuclear protein widely expressed in mammalian cells. This study aimed to comprehensively investigate the roles and mechanisms of HMGB1 in different tumors. Original data on HMGB1 expression, localization, potential interacting proteins, genetics were obtained from The Cancer Genome Atlas, Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, Human Protein Atlas, Compartmentalized Protein-Protein Interaction and cBioPortal databases. Then, correlation between HMGB1 expression levels and tumor stage, prognosis, potential pathways, tumor microenvironment, ESTIMATE score, immune-related genes, immune cell infiltration, microsatellite instability, tumor mutation burden, or anti-tumor drug resistance was investigated. The above results consistently indicated that high expression of HMGB1 protein may be related to clinical prognosis of HCC patients. Therefore, clinical tissues of HCC patients were selected to verify the differential expression of HMGB1 protein in HCC. The sensitivity of HMGB1-siRNA transfected HepG2 cells to sorafenib was assessed. HMGB1 was found to be differentially expressed in many tumors and normal tissues. HMGB1 was mainly located in the nucleus and might interact with proteins such as TLR2 and TLR4. Furthermore, HMGB1 expression was closely related to tumor stage, prognosis, tumor microenvironment, immune-related genes, immune cell infiltration, microsatellite instability, tumor mutation burden, and anti-tumor drug resistance and might be involved in different pathways of various tumors. Immunohistochemistry results further verified the differential expression of HMGB1 in HCC and paracancerous tissues. HMGB1-siRNA transfected HepG2 cells had a tendency to be more insensitive to sorafenib treatment compared to the control group. HMGB1 was differentially expressed in most tumors and normal tissues, and was closely related to the clinical stage, prognosis, immune infiltration, tumor microenvironment, and drug resistance of tumors. Therefore, HMGB1 may serve as a novel biomarker for predicting tumor prognosis, efficacy of immune checkpoint inhibitors, and a potential target for anti-tumor therapy.
Type
Publication
Journal of Inflammation Research, 16, 617-637
Status
Peer-reviewed Open access
publications
Muzi Ouyang (Mia)
Authors
PhD Candidate

I am Muzi Ouyang (欧阳木子) — I go by Mia. I am a PhD candidate in Chemistry at Tsinghua University, advised by Prof. Ying Tan (谭英) at the Institute of Biopharmaceutical and Health Engineering (iBHE) in Shenzhen. I work on targeted protein degradation: designing bioPROTACs that recruit E3 ligases to destroy proteins small molecules struggle to drug — and working out why that degradation sometimes fails.

My dissertation has two halves. The first is a dual-target bioPROTAC that co-degrades ERα and PI3K p85α, re-sensitizing tamoxifen-resistant breast cancer cells to endocrine therapy. The second is a KRAS-targeting degrader, where I found a resistance mutation in the hypervariable region that lets KRAS escape a multimerization-dependent platform, and used all-atom molecular dynamics to trace the conformational mechanism behind the escape.

Alongside the wet lab I work in computational protein design — Rosetta, ProteinMPNN and AlphaFold2 — including an end-to-end reproduction of the CLAIRE de novo binder-design pipeline, published openly with its debugging narrative. My training spans animal science, basic medicine and chemistry, which is why I move between wet-lab mechanism and computational design rather than choosing between them.

I expect to defend in June 2027 and am seeking postdoctoral positions starting in late 2027. If my work overlaps with your group’s, I’d be glad to hear from you — I’ll gladly send my CV. Write to me at mumumia.1009@gmail.com, or oymzmia@163.com if you are corresponding from within China.