对 HMGB1 在人类肿瘤中致癌功能的泛癌分析

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2024-11-07 DOI:10.1016/j.bbrep.2024.101851

Hui-min Yang , Xiang-ning Zhao , Xiao-ling Li , Xi Wang , Yu Pu , Dong-kai Wei , Zhe Li

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引用次数: 0

摘要

背景虽然许多研究都对高迁移率基团盒蛋白1（HMGB1）与癌症的关系进行了研究，但对其在泛癌症中的作用的深入研究尚未开展。本研究利用癌症基因组图谱（The Cancer Genome Atlas，TCGA）和基因表达总库（Gene Expression Omnibus，GEO）数据库研究了各种人类肿瘤中 HMGB1 基因表达的差异及其与生存的相关性。然后，利用 cBioPortal 工具分析了 HMGB1 的基因改变，并评估了免疫细胞浸润。最后，我们收集了 95 例各种类型实体瘤患者的临床样本，并利用面板测序技术进行了体细胞突变分析。结果在大部分肿瘤类型中，肿瘤组织中的 HMGB1 基因表达明显高于非肿瘤组织。在特定肿瘤类型中，HMGB1 基因表达的升高与总生存期、无进展生存期和无病生存期的缩短有关。HMGB1 的基因改变表明，HMGB1 的扩增和突变可能会影响乳腺癌（BRCA）和肝肝细胞癌（LIHC）的预后。BRCA 和间皮瘤（MESO）的癌相关成纤维细胞（CAFs）浸润与 HMGB1 基因表达之间存在联系。此外，HMGB1 的共表达分析表明，它与涉及 RNA 剪接、mRNA 处理和 mRNA 代谢过程调节的基因有关。此外，利用京都基因和基因组百科全书（KEGG）进行的通路分析发现，HMGB1 与 "乙型肝炎"、"病毒性癌变 "和 "肝细胞癌 "的致病机制有关。根据对 95 名不同实体瘤患者的体细胞突变分析，我们发现肝癌患者的 HMGB1 突变频率高于其他实体瘤患者。这一发现与我们的室内研究结果一致。此外，我们还发现 HMGB1 基因突变的频率在 95 例患者数据的前 20 个突变基因中名列前茅，这表明 HMGB1 在各种实体瘤的发展和预后中发挥着重要作用。

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

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.

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.