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BMC Oral Health
Published in: BMC Oral Health 1/2023

Open Access 01-12-2023 | Research

A novel hypoxia-associated gene signature for prognosis prediction in head and neck squamous cell carcinoma

Authors: Jingyi Luo, Yuejiao Huang, Jiahe Wu, Lin Dai, Mingyou Dong, Bo Cheng

Published in: BMC Oral Health | Issue 1/2023

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Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of head and neck, which seriously threatens human life and health. However, the mechanism of hypoxia-associated genes (HAGs) in HNSCC remains unelucidated. This study aims to establish a hypoxia-associated gene signature and the nomogram for predicting the prognosis of patients with HNSCC.

Methods

Previous literature reports provided a list of HAGs. The TCGA database provided genetic and clinical information on HNSCC patients. First, a hypoxia-associated gene risk model was constructed for predicting overall survival (OS) in HNSCC patients and externally validated in four GEO datasets (GSE27020, GSE41613, GSE42743, and GSE117973). Then, immune status and metabolic pathways were analyzed. A nomogram was constructed and assessed the predictive value. Finally, experimental validation of the core genes was performed by qRT-PCR.

Results

A HNSCC prognostic model was constructed based on 8 HAGs. This risk model was validated in four external datasets and exhibited high predictive value in various clinical subgroups. Significant differences in immune cell infiltration levels and metabolic pathways were found between high and low risk subgroups. The nomogram was highly accurate for predicting OS in HNSCC patients.

Conclusions

The 8 hypoxia-associated gene signature can serve as novel independent prognostic indicators in HNSCC patients. The nomogram combining the risk score and clinical stage enhanced predictive performance in predicting OS compared to the risk model and clinical characteristics alone.
Appendix
Available only for authorised users
Literature
1.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.PubMedCrossRef
2.
Solomon B, Young RJ, Rischin D. Head and neck squamous cell carcinoma: genomics and emerging biomarkers for immunomodulatory cancer treatments. Semin Cancer Biol. 2018;52(Pt 2):228–40.PubMedCrossRef
3.
Leemans CR, Snijders P, Brakenhoff RH. The molecular landscape of head and neck cancer. Nat Rev Cancer. 2018;18(5):269–82.PubMedCrossRef
4.
Caudell JJ, Gillison ML, Maghami E, Spencer S, Pfister DG, Adkins D, Birkeland AC, Brizel DM, Busse PM, Cmelak AJ, et al. NCCN guidelines(R) insights: head and neck cancers, version 1.2022. J Natl Compr Canc Ne. 2022;20(3):224–34.CrossRef
5.
Lakhani SR, Ashworth A. Microarray and histopathological analysis of tumours: the future and the past? Nat Rev Cancer. 2001;1(2):151–7.PubMedCrossRef
6.
Tirpe AA, Gulei D, Ciortea SM, Crivii C, Berindan-Neagoe I. Hypoxia: overview on hypoxia-mediated mechanisms with a focus on the role of HIF genes. Int J Mol Sci. 2019;20(24):6140.PubMedPubMedCentralCrossRef
7.
Nishida N, Kudo M. Oxidative stress and epigenetic instability in human hepatocarcinogenesis. Digest Dis. 2013;31(5–6):447–53.CrossRef
8.
Wu XZ, Xie GR, Chen D. Hypoxia and hepatocellular carcinoma: The therapeutic target for hepatocellular carcinoma. J Gastroen Hepatol. 2007;22(8):1178–82.CrossRef
9.
Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, Shu Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019;18(1):157.PubMedPubMedCentralCrossRef
10.
Baumeister P, Zhou J, Canis M, Gires O. Epithelial-to-mesenchymal transition-derived heterogeneity in head and neck squamous cell carcinomas. Cancers. 2021;13(21):5355.PubMedPubMedCentralCrossRef
11.
Nascimento-Filho C, Webber LP, Borgato GB, Goloni-Bertollo EM, Squarize CH, Castilho RM. Hypoxic niches are endowed with a protumorigenic mechanism that supersedes the protective function of PTEN. Faseb J. 2019;33(12):13435–49.PubMedPubMedCentralCrossRef
12.
Sarnella A, Ferrara Y, Auletta L, Albanese S, Cerchia L, Alterio V, De Simone G, Supuran CT, Zannetti A. Inhibition of carbonic anhydrases IX/XII by SLC-0111 boosts cisplatin effects in hampering head and neck squamous carcinoma cell growth and invasion. J Exp Clin Canc Res. 2022;41(1):122.CrossRef
13.
Ding Z, Li H, Yu D. Development and validation of a hypoxia-related gene pair signature to predict overall survival in head and neck squamous cell carcinoma. Eur Arch Oto-Rhino-L. 2021;278(10):3973–83.CrossRef
14.
Ning XH, Li NY, Qi YY, Li SC, Jia ZK, Yang JJ. Identification of a hypoxia-related gene model for predicting the prognosis and formulating the treatment strategies in kidney renal clear cell carcinoma. Front Oncol. 2021;11:806264.PubMedCrossRef
15.
Wu J, Cai H, Lei Z, Li C, Hu Y, Zhang T, Zhu H, Lu Y, Cao J, Hu X. Expression pattern and diagnostic value of ferroptosis-related genes in acute myocardial infarction. Front Cardiovasc Med. 2022;9:993592.PubMedPubMedCentralCrossRef
16.
Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T, Zhou L, Tang W, Zhan L, et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation (Camb). 2021;2(3):100141.PubMed
17.
Wu J, Luo J, Cai H, Li C, Lei Z, Lu Y, Ni L, Cao J, Cheng B, Hu X. Expression pattern and molecular mechanism of oxidative stress-related genes in myocardial ischemia-reperfusion injury. J Cardiovasc Dev Dis. 2023;10(2):79.PubMedPubMedCentral
18.
Yoshihara K, Shahmoradgoli M, Martinez E, Vegesna R, Kim H, Torres-Garcia W, Trevino V, Shen H, Laird PW, Levine DA, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.PubMedCrossRef
19.
Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, Li B, Liu XS. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48(W1):W509–14.PubMedPubMedCentralCrossRef
20.
Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, Selves J, Laurent-Puig P, Sautes-Fridman C, Fridman WH, et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 2016;17(1):218.PubMedPubMedCentralCrossRef
21.
Newman AM, Steen CB, Liu CL, Gentles AJ, Chaudhuri AA, Scherer F, Khodadoust MS, Esfahani MS, Luca BA, Steiner D, et al. Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat Biotechnol. 2019;37(7):773–82.PubMedPubMedCentralCrossRef
22.
23.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. P Natl Acad Sci USA. 2005;102(43):15545–50.CrossRef
24.
Bhat GR, Hyole RG, Li J. Head and neck cancer: Current challenges and future perspectives. Adv Cancer Res. 2021;152:67–102.PubMedCrossRef
25.
Ren Z, Zhang L, Ding W, Luo Y, Shi Z, Shrestha B, Kan X, Zhang Z, Ding J, He H, et al. Development and validation of a novel survival model for head and neck squamous cell carcinoma based on autophagy-related genes. Genomics. 2021;113(1 Pt 2):1166–75.PubMedCrossRef
26.
Zhou L, Jiang J, Huang Z, Jin P, Peng L, Luo M, Zhang Z, Chen Y, Xie N, Gao W, et al. Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/beta-catenin signaling to promote colorectal cancer progression by preventing m(6)A-mediated degradation of STEAP3 mRNA. Mol Cancer. 2022;21(1):168.PubMedPubMedCentralCrossRef
27.
Zandberg DP, Menk AV, Velez M, Normolle D, DePeaux K, Liu A, Ferris RL, Delgoffe GM. Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck. J Immunother Cancer. 2021;9(5):e002088.PubMedPubMedCentralCrossRef
28.
Wen K, Yan Y, Shi J, Hu L, Wang W, Liao H, Li H, Zhu Y, Mao K, Xiao Z. Construction and validation of a combined ferroptosis and hypoxia prognostic signature for hepatocellular carcinoma. Front Mol Biosci. 2021;8:809672.PubMedPubMedCentralCrossRef
29.
Xiong Z, Huang W, Zhong W, Fu J, Feng J, Wang X, Ling F. Breast cancer subtypes based on hypoxia-related gene sets identify potential therapeutic agents. Front Mol Biosci. 2022;9:900005.PubMedPubMedCentralCrossRef
30.
Cai D, Zhou Z, Wei G, Wu P, Kong G. Construction and verification of a novel hypoxia-related lncRNA signature related with survival outcomes and immune microenvironment of bladder urothelial carcinoma by weighted gene co-expression network analysis. Front Genet. 2022;13:952369.PubMedPubMedCentralCrossRef
31.
Wang E, Li Y, Ming R, Wei J, Du P, Zhou P, Zong S, Xiao H. The prognostic value and immune landscapes of a m(6)A/m(5)C/m(1)A-Related LncRNAs signature in head and neck squamous cell carcinoma. Front Cell Dev Biol. 2021;9:718974.PubMedPubMedCentralCrossRef
32.
Wu Y, Yang L, Zhang L, Zheng X, Xu H, Wang K, Weng X. Identification of a four-gene signature associated with the prognosis prediction of lung adenocarcinoma based on integrated bioinformatics analysis. Genes Basel. 2022;13(2):238.PubMedPubMedCentralCrossRef
33.
Huang KC, Park DC, Ng SK, Lee JY, Ni X, Ng WC, Bandera CA, Welch WR, Berkowitz RS, Mok SC, et al. Selenium binding protein 1 in ovarian cancer. Int J Cancer. 2006;118(10):2433–40.PubMedCrossRef
34.
Zhu C, Wang S, Du Y, Dai Y, Huai Q, Li X, Du Y, Dai H, Yuan W, Yin S, et al. Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is associated with immunotherapy efficacy and survival in colorectal cancer. BMC Gastroenterol. 2022;22(1):437.PubMedPubMedCentralCrossRef
35.
Hoffmann C, Mao X, Brown-Clay J, Moreau F, Al AA, Wurzer H, Sousa B, Schmitt F, Berchem G, Janji B, et al. Hypoxia promotes breast cancer cell invasion through HIF-1alpha-mediated up-regulation of the invadopodial actin bundling protein CSRP2. Sci Rep-UK. 2018;8(1):10191.CrossRef
36.
Wang J, Guan X, Zhang Y, Ge S, Zhang L, Li H, Wang X, Liu R, Ning T, Deng T, et al. Exosomal miR-27a derived from gastric cancer cells regulates the transformation of fibroblasts into cancer-associated fibroblasts. Cell Physiol Biochem. 2018;49(3):869–83.PubMedCrossRef
37.
Wang SJ, Wang PZ, Gale RP, Qin YZ, Liu YR, Lai YY, Jiang H, Jiang Q, Zhang XH, Jiang B, et al. Cysteine and glycine-rich protein 2 (CSRP2) transcript levels correlate with leukemia relapse and leukemia-free survival in adults with B-cell acute lymphoblastic leukemia and normal cytogenetics. Oncotarget. 2017;8(22):35984–6000.PubMedPubMedCentralCrossRef
38.
Huang Z, Lan T, Wang J, Chen Z, Zhang X. Identification and validation of seven RNA binding protein genes as a prognostic signature in oral cavity squamous cell carcinoma. Bioengineered. 2021;12(1):7248–62.PubMedPubMedCentralCrossRef
39.
Weiss CM, Trobaugh DW, Sun C, Lucas TM, Diamond MS, Ryman KD, Klimstra WB. The interferon-induced exonuclease ISG20 exerts antiviral activity through upregulation of type I interferon response proteins. mSphere. 2018;3(5):e00209.PubMedPubMedCentralCrossRef
40.
Gao M, Lin Y, Liu X, Li Y, Zhang C, Wang Z, Wang Z, Wang Y, Guo Z. ISG20 promotes local tumor immunity and contributes to poor survival in human glioma. Oncoimmunology. 2019;8(2):e1534038.PubMedCrossRef
41.
Kisoda S, Shao W, Fujiwara N, Mouri Y, Tsunematsu T, Jin S, Arakaki R, Ishimaru N, Kudo Y. Prognostic value of partial EMT-related genes in head and neck squamous cell carcinoma by a bioinformatic analysis. Oral Dis. 2020;26(6):1149–56.
42.
Law AY, Wong CK. Stanniocalcin-2 is a HIF-1 target gene that promotes cell proliferation in hypoxia. Exp Cell Res. 2010;316(3):466–76.PubMedCrossRef
43.
Schmidt V, Sieckmann T, Kirschner KM, Scholz H. WT1 regulates HOXB9 gene expression in a bidirectional way. BBA Gene Regul Mech. 2021;1864(11–12):194764.
44.
Liu J, Liu F, Li X, Song X, Zhou L, Jie J. Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing. Tumour Biol. 2017;39(7):1393374765.CrossRef
45.
Wang S, Qu Y, Xia P, Chen Y, Zhu X, Zhang J, Wang G, Tian Y, Ying J, Fan Z. Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer. CELL RES. 2020;30(7):610–22.PubMedPubMedCentralCrossRef
46.
Li SR, Man QW, Liu B. Development and validation of a novel hypoxia-related signature for prognostic and immunogenic evaluation in head and neck squamous cell carcinoma. Front Oncol. 2022;12:943945.PubMedPubMedCentralCrossRef
47.
Li H, Wang J, He L, Zhang F, Meng Q, Huang J, Li Y, Liu R, Yang X, Wei J. Construction of a combined hypoxia and EMT index for head and neck squamous cell carcinoma. Front Cell Dev Biol. 2022;10:961858.PubMedPubMedCentralCrossRef
48.
Wang H, Zheng L. Construction of a hypoxia-derived gene model to predict the prognosis and therapeutic response of head and neck squamous cell carcinoma. Sci Rep UK. 2022;12(1):13538.CrossRef
Metadata
Title
A novel hypoxia-associated gene signature for prognosis prediction in head and neck squamous cell carcinoma
Authors
Jingyi Luo
Yuejiao Huang
Jiahe Wu
Lin Dai
Mingyou Dong
Bo Cheng
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-023-03489-8

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