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

Lin, Tong; Zheng, Lin; Peng, Lisheng

doi:10.3389/fgene.2021.764245

Cited by 11 publications

(13 citation statements)

References 58 publications

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“…59 Another study analyzed the role of HMGB protein family in various tumors. 60 The results showed that HMGBs were highly expressed in various tumors, including COAD, DLBC, LGG, PAAD, READ, STAD and THYM. High HMGB1 expression was associated with worse OS in ACC and KICH and higher OS in THYM.…”

Section: Discussionmentioning

confidence: 96%

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

Guan¹,

Zhong²,

Ma³

et al. 2023

JIR

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Background 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. Methods 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. Results 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. Conclusions 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.

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Section: Discussionmentioning

confidence: 96%

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

Guan¹,

Zhong²,

Ma³

et al. 2023

JIR

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“…In our study, RAC3 was significantly upregulated in tumor samples and exhibited widespread CNV alterations. HMGB3 was found to be overexpressed in a variety of cancers, including breast invasive carcinoma, sarcoma, skin cutaneous melanoma, ovarian serous cystadenocarcinoma, and acute myeloid leukemia (53,54). The upregulation of the HMGB3 gene has been implicated in tumorigenesis and chemotherapy resistance via various mechanisms (54).…”

Section: Discussionmentioning

confidence: 99%

Deciphering comprehensive features of tumor microenvironment controlled by chromatin regulators to predict prognosis and guide therapies in uterine corpus endometrial carcinoma

Tian

Liu

et al. 2023

Front. Immunol.

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BackgroundDysregulation of chromatin regulators (CRs) can perturb the tumor immune microenvironment, but the underlying mechanism remains unclear. We focused on uterine corpus endometrial carcinoma (UCEC) and used gene expression data from TCGA-UCEC to investigate this mechanism.MethodsWe used weighted gene co-expression network analysis (WGCNA) and consensus clustering algorithm to classify UCEC patients into Cluster_L and Cluster_H. TME-associated CRs were identified using WGCNA and differential gene expression analysis. A CR risk score (CRRS) was constructed using univariate Cox and LASSO-Cox regression analyses. A nomogram was developed based on CRRS and clinicopathologic factors to predict patients' prognosis.ResultsLower CRRS was associated with lower grade, more benign molecular subtypes, and improved survival. Patients with low CRRS showed abundant immune infiltration, a higher mutation burden, fewer CNVs, and better response to immunotherapy. Moreover, low CRRS patients were more sensitive to 24 chemotherapeutic agents.ConclusionA comprehensive assessment of CRRS could identify immune activation and improve the efficacy of UCEC treatments.

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“…High TMB score was associated with the poor prognosis of PAAD patients ( Li L. et al, 2021 ). Meanwhile, high TMB could increase the emergence of neoantigens, thereby enhancing immunotherapy response ( Lin et al, 2021 ). In this study, we found ceRNA risk score was positively associated with TMB score.…”

Section: Discussionmentioning

confidence: 99%

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Tan

Liu

et al. 2022

Front. Pharmacol.

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Pancreatic adenocarcinoma (PAAD) is a malignant cancer with high incidence and mortality. Glycometabolic rearrangements (aerobic glycolysis) is a hallmark of PAAD and contributes to tumorigenesis and progression through numerous mechanisms. This study aimed to identify a novel glycolysis-related lncRNA-miRNA-mRNA ceRNA signature in PAAD and explore its potential molecular function. We first calculated the glycolysis score for each PAAD patient by the ssGSEA algorithm and found that patients with higher hallmark glycolysis scores had poorer prognosis. Subsequently, we obtained a novel glycolysis-related LINC02432/hsa-miR-98–5p/HK2 axis from the TCGA and GEO databases using comprehensive bioinformatics analysis and developed a nomogram to predict overall survival. Furthermore, functional characterization analysis revealed that LINC02432/hsa-miR-98–5p/HK2 axis risk score was negatively correlated with ferroptosis. The tumor immune infiltration analysis suggested positive correlations between ceRNA risk score and infiltrated M0 macrophage levels in PAAD. Correlation analysis found that ceRNA risk scores were positively correlated with four chemokines (CXCL3, CXCL5, CXCL8 and CCL20) and one immune checkpoint gene (SIGLEC15). Meanwhile, tumor mutation burden (TMB), an indicator for predicting response to immunotherapy, was positively correlated with ceRNA risk score. Finally, the drug sensitivity analysis showed that the high-risk score patients might be more sensitive to EGFR, MEK and ERK inhibitors than low-risk score patients. In conclusion, our study suggested that LINC02432/hsa-miR-98–5p/HK2 axis may serve as a novel diagnostic, prognostic, and therapeutic target in PAAD treatment.

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

Cited by 11 publications

References 58 publications

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

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

Deciphering comprehensive features of tumor microenvironment controlled by chromatin regulators to predict prognosis and guide therapies in uterine corpus endometrial carcinoma

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

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