A pan-cancer analysis of high mobility group box 1 and its role in human tumorigenesis
Understanding the specific and co-driving mechanisms of carcinogenesis in human tumors is indispensable for cancer research and can guide the development of effective treatment methods for tumors. High mobility group box 1 (HMGB1) participates in a variety of physiological processes of the body and has an inseparable relationship with tumors. In this study, The Cancer Genome Atlas, Gene Expression Omnibus database, Human Protein Atlas, and bioinformatic tools were used to conduct pan-cancer analysis of HMGB1 in various cancers so as to elucidate its role in human tumorigenesis. We analyzed and evaluated the expression of HMGB1 in tumors, and discovered that overexpression of HMGB1 usually indicated poor overall survival of adrenocortical carcinoma (P < 0.01) and lung adenocarcinoma (LUAD) (P < 0.05). High HMGB1 expression is also associated with unfavorable disease-free survival for patients with adrenocortical carcinoma (P < 0.001), cervical squamous cell carcinoma and endocervical adenocarcinoma (P < 0.01), head and neck squamous cell carcinoma (P < 0.05), LUAD (P < 0.05), and sarcoma (P < 0.05). The potential mechanism of HMGB1-mediated tumorigenesis is also discussed. In conclusion, our pan-cancer analysis offers a comprehensive description of the carcinogenic roles of HMGB1 in a variety of human cancers.
Blum A, Wang P, Zenklusen JC, 2018, SnapShot: TCGA-Analyzed tumors. Cell, 173(2): 530. https://doi.org/10.1016/j.cell.2018.03.059
Tomczak K, Czerwińska P,Wiznerowicz M, 2015, The cancer genome atlas (TCGA): An immeasurable source of knowledge. Contemp Oncol (Pozn), 19(1a): A68–A77. https://doi.org/10.5114/wo.2014.47136
Clough E, Barrett T, 2016, The gene expression omnibus database. Methods Mol Biol, 1418: 93–110. https://doi.org/10.1007/978-1-4939-3578-9_5
Ferrari S, Finelli P, Rocchi M, et al., 1996, The active gene that encodes human high mobility group 1 protein (HMG1) contains introns and maps to chromosome 13. Genomics, 35(2): 367–371. https://doi.org/10.1006/geno.1996.0369
Goodwin GH, Sanders C, Johns EW, 1973, A new group of chromatin-associated proteins with a high content of acidic and basic amino acids. Eur J Biochem, 38(1): 14–19. https://doi.org/10.1111/j.1432-1033.1973.tb03026.x
Li J, Kokkola R, Tabibzadeh S, et al., 2003, Structural basis for the proinflammatory cytokine activity of high mobility group box 1. Mol Med, 9(1–2): 37–45.
Kang R, Zhang Q, Zeh HJ 3rd, et al., 2013, HMGB1 in cancer: Good, bad, or both? Clin Cancer Res, 19(15): 4046–4057. https://doi.org/10.1158/1078-0432.Ccr-13-0495
Huebener P, Gwak GY, Pradere JP, et al., 2014, High-mobility group box 1 is dispensable for autophagy, mitochondrial quality control, and organ function in vivo. Cell Metab, 19(3): 539–547. https://doi.org/10.1016/j.cmet.2014.01.014
Vargas TR, Apetoh L, 2017, Danger signals: Chemotherapy enhancers? Immunol Rev, 280(1): 175–193. https://doi.org/10.1111/imr.12581
Gao Q, Wang S, Chen X, et al., 2019, Cancer-cell-secreted CXCL11 promoted CD8(+) T cells infiltration through docetaxel-induced-release of HMGB1 in NSCLC. J Immunother Cancer, 7(1): 42. https://doi.org/10.1186/s40425-019-0511-6
Tang Z, Kang B, Li C, et al., 2019, GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res, 47(W1): W556–W560. https://doi.org/10.1093/nar/gkz430
Chen F, Chandrashekar DS, Varambally S, et al., 2019, Pan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers. Nat Commun, 10(1): 5679. https://doi.org/10.1038/s41467-019-13528-0
Gao J, Aksoy BA, Dogrusoz U, et al., 2013, Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal, 6(269): pl1. https://doi.org/10.1126/scisignal.2004088
Jiao XD, Qin BD, You P, et al., 2018, The prognostic value of TP53 and its correlation with EGFR mutation in advanced non-small cell lung cancer, an analysis based on cBioPortal data base. Lung Cancer, 123: 70–75. https://doi.org/10.1016/j.lungcan.2018.07.003
Cerami E, Gao J, Dogrusoz U, et al., 2012, The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov, 2(5): 401–404. https://doi.org/10.1158/2159-8290.Cd-12-0095
Bardou P, Mariette J, Escudié F, et al., 2014, jvenn: An interactive Venn diagram viewer. BMC Bioinformatics, 15(1): 293. https://doi.org/10.1186/1471-2105-15-293
Cui X, Zhang X, Liu M, et al., 2020, A pan-cancer analysis of the oncogenic role of staphylococcal nuclease domain-containing protein 1 (SND1) in human tumors. Genomics, 112(6): 3958–3967. https://doi.org/10.1016/j.ygeno.2020.06.044
Fridman WH, Galon J, Dieu-Nosjean MC, et al., 2011, Immune infiltration in human cancer: Prognostic significance and disease control. Curr Top Microbiol Immunol, 344: 1–24. https://doi.org/10.1007/82_2010_46
Steven A, Seliger B, 2018, The role of immune escape and immune cell infiltration in breast cancer. Breast Care (Basel), 13(1): 16–21. https://doi.org/10.1159/000486585
Domingues P, González-Tablas M, Otero Á, et al., 2016, Tumor infiltrating immune cells in gliomas and meningiomas. Brain Behav Immun, 53: 1–15. https://doi.org/10.1016/j.bbi.2015.07.019
Chen X, Song E, 2019, Turning foes to friends: Targeting cancer-associated fibroblasts. Nat Rev Drug Discov, 18(2): 99–115. https://doi.org/10.1038/s41573-018-0004-1
Kwa MQ, Herum KM, Brakebusch C, 2019, Cancer-associated fibroblasts: How do they contribute to metastasis? Clin Exp Metastasis, 36(2): 71–86. https://doi.org/10.1007/s10585-019-09959-0
Biffi G, Tuveson DA, 2021, Diversity and biology of cancer-associated fibroblasts. Physiol Rev, 101(1): 147–176. https://doi.org/10.1152/physrev.00048.2019
Kumari T, Kumar B, 2018, High-mobility group box 1 protein (HMGB1) gene polymorphisms and cancer susceptibility: A comprehensive meta-analysis. Clin Chim Acta, 483: 170–182. https://doi.org/10.1016/j.cca.2018.04.042
Tang D, Kang R, Zeh HJ 3rd, et al., 2010, High-mobility group box 1 and cancer. Biochim Biophys Acta, 1799(1–2): 131–140. https://doi.org/10.1016/j.bbagrm.2009.11.014
Sims GP, Rowe DC, Rietdijk ST, et al., 2010, HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol, 28: 367–388. https://doi.org/10.1146/annurev.immunol.021908.132603
Andersson U, Tracey KJ, 2011, HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol, 29: 139–162. https://doi.org/10.1146/annurev-immunol-030409-101323
Stros M, 2010, HMGB proteins: Interactions with DNA and chromatin. Biochim Biophys Acta, 1799(1–2): 101–113. https://doi.org/10.1016/j.bbagrm.2009.09.008
Lange SS, Vasquez KM, 2009, HMGB1: The jack-of-all-trades protein is a master DNA repair mechanic. Mol Carcinog, 48(7): 571–580. https://doi.org/10.1002/mc.20544
Zhang QY, Wu LQ, Zhang T, et al., 2015, Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1/2. Oncol Rep, 33(4): 1630–1638. https://doi.org/10.3892/or.2015.3782
Zhang W, An F, Xia M, et al., 2019, Increased HMGB1 expression correlates with higher expression of c-IAP2 and pERK in colorectal cancer. Medicine (Baltimore), 98(3): e14069. https://doi.org/10.1097/md.0000000000014069
Ye L, Zhang Q, Cheng Y, et al., 2018, Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1(+) regulatory B cell expansion. J Immunother Cancer, 6(1): 145. https://doi.org/10.1186/s40425-018-0451-6
Zuo Z, Che X, Wang Y, et al., 2014, High mobility group Box-1 inhibits cancer cell motility and metastasis by suppressing activation of transcription factor CREB and nWASP expression. Oncotarget, 5(17): 7458–7470. https://doi.org/10.18632/oncotarget.2150
Hou X, Lin S, Liu Y, et al., 2022, Analysis of the tumor microenvironment and mutation burden identifies prognostic features in thymic epithelial tumors. Am J Cancer Res, 12(5): 2387–2396.
Huang C, Huang Z, Zhao X, et al., 2018, Overexpression of high mobility group box 1 contributes to progressive clinicopathological features and poor prognosis of human bladder urothelial carcinoma. Onco Targets Ther, 11: 2111–2120. https://doi.org/10.2147/ott.S155745
Wang XH, Zhang SY, Shi M, et al., 2020, HMGB1 promotes the proliferation and metastasis of lung cancer by activating the Wnt/β-catenin pathway. Technol Cancer Res Treat, 19: 1533033820948054. https://doi.org/10.1177/1533033820948054
Ren Y, Cao L, Wang L, et al., 2021, Autophagic secretion of HMGB1 from cancer-associated fibroblasts promotes metastatic potential of non-small cell lung cancer cells via NFκB signaling. Cell Death Dis, 12(10): 858. https://doi.org/10.1038/s41419-021-04150-4
Jiao D, Zhang J, Chen P, et al., 2021, HN1L promotes migration and invasion of breast cancer by up-regulating the expression of HMGB1. J Cell Mol Med, 25(1): 397–410. https://doi.org/10.1111/jcmm.16090
He H, Wang X, Chen J, et al., 2019, High-mobility group box 1 (HMGB1) promotes angiogenesis and tumor migration by regulating hypoxia-inducible factor 1 (HIF-1α) expression via the phosphatidylinositol 3-Kinase (PI3K)/AKT signaling pathway in breast cancer cells. Med Sci Monit, 25: 2352–2360. https://doi.org/10.12659/msm.915690
Liang L, Fu J, Wang S, et al., 2020, MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1. Acta Pharm Sin B, 10(6): 1036–1046. https://doi.org/10.1016/j.apsb.2019.11.009
Li P, Xu M, Cai H, et al., 2019, The effect of HMGB1 on the clinicopathological and prognostic features of cervical cancer. Biosci Rep, 39(5): BSR20181016. https://doi.org/10.1042/bsr20181016
Xu Y, Chen Z, Zhang G, et al., 2015, HMGB1 overexpression correlates with poor prognosis in early-stage squamous cervical cancer. Tumour Biol, 36(11): 9039–9047. https://doi.org/10.1007/s13277-015-3624-7
Liu Y, Xie C, Zhang X, et al., 2010, Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance. Eur J Cancer, 46(16): 3007–3015. https://doi.org/10.1016/j.ejca.2010.07.016