Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer

Objective: To assess the correlation between HMGB1 expression and the patient prognosis in a multicancer context. Methods: The potential oncogenic role of HMGB1 was explored in forty tumors through the TCGA, GEO, and Oncomine datasets. We analyzed the clinical prognostic value and antitumor immunoth...

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Main Authors: Huijiao Lu, Mengyi Zhu, Lin Qu, Hongwei Shao, Rongxin Zhang, Yan Li
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/19/4875
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author Huijiao Lu
Mengyi Zhu
Lin Qu
Hongwei Shao
Rongxin Zhang
Yan Li
author_facet Huijiao Lu
Mengyi Zhu
Lin Qu
Hongwei Shao
Rongxin Zhang
Yan Li
author_sort Huijiao Lu
collection DOAJ
description Objective: To assess the correlation between HMGB1 expression and the patient prognosis in a multicancer context. Methods: The potential oncogenic role of HMGB1 was explored in forty tumors through the TCGA, GEO, and Oncomine datasets. We analyzed the clinical prognostic value and antitumor immunotherapy of HMGB1 in a multicancer context using GEO (GSE111636). Results: High expression of HMGB1 is present in multicancer cases, and its low expression is closely associated with the prognostic survival of patients, in terms of both overall and disease-free survival in ACC and LUAD. Further investigation revealed that the high expression of gastric and lung cancer is closely associated with low risk and better prognosis of patients based on COX and Kaplan–Meier analysis of OS, FP and PPS. HMGB1 expression was found to be significantly correlated with cancer-associated fibroblast and CD8<sup>+</sup> T cell infiltration in the TME. The analysis of GO functional annotation/KEGG pathways indicates that HMGB1 may regulate tumor immunity-related pathways, such as the tumor immunotherapy response in colorectal cancer. The function of four genes as hubs are confirmed by in vitro HMGB1 knockdown which led to inhibition of cell proliferation and metastasis in SW620 and SW480 cells. Conclusion: HMGB1 is a potential novel biomarker for improving clinical prognosis and antitumor immunotherapy efficacy. CDK1, HMGB2, SSRP1, and H2AFV may serve as key nodes for HMGB1 in colorectal cancer.
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spelling doaj.art-f230fe4798c94fbcae94fc6a700ce03a2023-11-23T19:58:04ZengMDPI AGCancers2072-66942022-10-011419487510.3390/cancers14194875Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal CancerHuijiao Lu0Mengyi Zhu1Lin Qu2Hongwei Shao3Rongxin Zhang4Yan Li5Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Institute of Basic Medical Sciences and Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaGuangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Institute of Basic Medical Sciences and Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaGuangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Institute of Basic Medical Sciences and Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaGuangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Institute of Basic Medical Sciences and Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaGuangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Institute of Basic Medical Sciences and Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaGuangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Institute of Basic Medical Sciences and Department of Biotechnology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaObjective: To assess the correlation between HMGB1 expression and the patient prognosis in a multicancer context. Methods: The potential oncogenic role of HMGB1 was explored in forty tumors through the TCGA, GEO, and Oncomine datasets. We analyzed the clinical prognostic value and antitumor immunotherapy of HMGB1 in a multicancer context using GEO (GSE111636). Results: High expression of HMGB1 is present in multicancer cases, and its low expression is closely associated with the prognostic survival of patients, in terms of both overall and disease-free survival in ACC and LUAD. Further investigation revealed that the high expression of gastric and lung cancer is closely associated with low risk and better prognosis of patients based on COX and Kaplan–Meier analysis of OS, FP and PPS. HMGB1 expression was found to be significantly correlated with cancer-associated fibroblast and CD8<sup>+</sup> T cell infiltration in the TME. The analysis of GO functional annotation/KEGG pathways indicates that HMGB1 may regulate tumor immunity-related pathways, such as the tumor immunotherapy response in colorectal cancer. The function of four genes as hubs are confirmed by in vitro HMGB1 knockdown which led to inhibition of cell proliferation and metastasis in SW620 and SW480 cells. Conclusion: HMGB1 is a potential novel biomarker for improving clinical prognosis and antitumor immunotherapy efficacy. CDK1, HMGB2, SSRP1, and H2AFV may serve as key nodes for HMGB1 in colorectal cancer.https://www.mdpi.com/2072-6694/14/19/4875HMGB1clinical prognosisantitumor immune responsescancer-associated fibroblasts (CAFs)tumor immune microenvironment (TME)immune checkpoints molecules (ICPs)
spellingShingle Huijiao Lu
Mengyi Zhu
Lin Qu
Hongwei Shao
Rongxin Zhang
Yan Li
Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer
Cancers
HMGB1
clinical prognosis
antitumor immune responses
cancer-associated fibroblasts (CAFs)
tumor immune microenvironment (TME)
immune checkpoints molecules (ICPs)
title Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer
title_full Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer
title_fullStr Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer
title_full_unstemmed Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer
title_short Oncogenic Role of HMGB1 as An Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer
title_sort oncogenic role of hmgb1 as an alarming in robust prediction of immunotherapy response in colorectal cancer
topic HMGB1
clinical prognosis
antitumor immune responses
cancer-associated fibroblasts (CAFs)
tumor immune microenvironment (TME)
immune checkpoints molecules (ICPs)
url https://www.mdpi.com/2072-6694/14/19/4875
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