A Comprehensive Prognostic Score for Head and Neck Squamous Cancer Driver Genes and Phenotype Traits

Overview

Journal Discov Oncol

Publisher Springer

Specialty Oncology

Date 2023 Oct 28

PMID 37897503

Authors

Wen Zeng

Fangfang Xie

Yiyun Pan

Zhengcong Chen

Hailong Chen

Xiaomei Liu

Keqiang Tian

Dechang Xu

Affiliations

Soon will be listed here.

Abstract

Background: Head and neck squamous cancer (HNSCC) presents variable phenotype and progression features. Clinically applicable, high-accuracy multifactorial prognostic models for HNSCC survival outcomes are warranted and an active area of research. This study aimed to construct a comprehensive prognostic tool for HNSCC overall survival by integrating cancer driver genes with tumor clinical and phenotype information.

Methods: Key overall survival-related cancer driver genes were screened from among main effector and reciprocal gene pairs using TCGA data using univariate Cox proportional hazard regression analysis. Independent validation was performed using the GSE41613 dataset. The main effector genes among these were selected using LASSO regression and transcriptome score modeling was performed using multivariate Cox regression followed by validation analysis of the prognostic score. Next, multivariate Cox regression analysis was performed using the transcriptome score combined with age, grade, gender, and stage. An 'Accurate Prediction Model of HNSCC Overall Survival Score' (APMHO) was computed and validated. Enriched functional pathways, gene mutational landscape, immune cell infiltration, and immunotherapy sensitivity markers associated with high and low APMHO scores were analyzed.

Results: Screening 107 overall survival-related cancer genes and 402 interacting gene pairs, 6 genes: CRLF2, HSP90AA1, MAP2K1, PAFAH1B2, MYCL and SET genes, were identified and a transcriptional score was obtained. Age, stage and transcriptional score were found to be significant predictors in Cox regression analysis and used to construct a final APMHO model showing an AUC > 0.65 and validated. Transcriptional score, age, pathologic_N, pathologic_T, stage, and TCGA_subtype were significantly different in distribution between high and low APMHO groups. High APMHO samples showed significantly higher mutation rate, enriched tumor-related pathways including Hypoxia, unfold_protein_response, Glycolysis, and mTORC1 signaling, along with differences in immune cell infiltration and immune checkpoint, interferon-γ pathway and m6A regulator expression patterns.

Conclusion: The APMHO score combining transcriptional and clinical variables showed good prognostic ability for HNSCC overall survival outcomes and was associated with different patterns of phenotypical features, immune and mutational landscape, and immunotherapy sensitivity marker expression. Future studies should validate this score in independent clinical cohorts.

Citing Articles

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La Banca V, De Domenico S, Nicolai S, Gatti V, Scalera S, Maugeri M Int J Mol Sci. 2024; 25(16).

PMID: 39201428 PMC: 11354449. DOI: 10.3390/ijms25168741.

References

Fitzmaurice C, Allen C, Barber R, Barregard L, Bhutta Z, Brenner H . Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2016; 3(4):524-548. PMC: 6103527. DOI: 10.1001/jamaoncol.2016.5688. View

Schinke H, Pan M, Akyol M, Zhou J, Shi E, Kranz G . SLUG-related partial epithelial-to-mesenchymal transition is a transcriptomic prognosticator of head and neck cancer survival. Mol Oncol. 2021; 16(2):347-367. PMC: 8763659. DOI: 10.1002/1878-0261.13075. View

Lohavanichbutr P, Mendez E, Holsinger F, Rue T, Zhang Y, Houck J . A 13-gene signature prognostic of HPV-negative OSCC: discovery and external validation. Clin Cancer Res. 2013; 19(5):1197-203. PMC: 3593802. DOI: 10.1158/1078-0432.CCR-12-2647. View

Weber P, Kunstner A, Hess J, Unger K, Marschner S, Idel C . Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer. Clin Cancer Res. 2021; 28(5):1038-1052. DOI: 10.1158/1078-0432.CCR-21-2244. View

Kuss I, Donnenberg A, Gooding W, Whiteside T . Effector CD8+CD45RO-CD27-T cells have signalling defects in patients with squamous cell carcinoma of the head and neck. Br J Cancer. 2003; 88(2):223-30. PMC: 2377049. DOI: 10.1038/sj.bjc.6600694. View

Li Y, Chen Y, Miao L, Wang Y, Yu M, Yan X . Stress-induced upregulation of TNFSF4 in cancer-associated fibroblast facilitates chemoresistance of lung adenocarcinoma through inhibiting apoptosis of tumor cells. Cancer Lett. 2020; 497:212-220. DOI: 10.1016/j.canlet.2020.10.032. View

Chabanon R, Postel-Vinay S . A Novel Synthetic Lethal Approach to Target MYC-Driven Cancers. Cancer Res. 2022; 82(6):969-971. DOI: 10.1158/0008-5472.CAN-22-0302. View

Sobral L, Sousa L, Coletta R, Cabral H, Greene L, Tajara E . Stable SET knockdown in head and neck squamous cell carcinoma promotes cell invasion and the mesenchymal-like phenotype in vitro, as well as necrosis, cisplatin sensitivity and lymph node metastasis in xenograft tumor models. Mol Cancer. 2014; 13:32. PMC: 3936887. DOI: 10.1186/1476-4598-13-32. View

Merlo L, Peng W, Mandik-Nayak L . Impact of IDO1 and IDO2 on the B Cell Immune Response. Front Immunol. 2022; 13:886225. PMC: 9043893. DOI: 10.3389/fimmu.2022.886225. View

10.

De Cecco L, Nicolau M, Giannoccaro M, Daidone M, Bossi P, Locati L . Head and neck cancer subtypes with biological and clinical relevance: Meta-analysis of gene-expression data. Oncotarget. 2015; 6(11):9627-42. PMC: 4496244. DOI: 10.18632/oncotarget.3301. View

11.

Howard F, Kochanny S, Koshy M, Spiotto M, Pearson A . Machine Learning-Guided Adjuvant Treatment of Head and Neck Cancer. JAMA Netw Open. 2020; 3(11):e2025881. PMC: 7677764. DOI: 10.1001/jamanetworkopen.2020.25881. View

12.

Fenoglio D, Belgioia L, Parodi A, Missale F, Bacigalupo A, Tarke A . Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28- T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer. Cancers (Basel). 2021; 13(9). PMC: 8124419. DOI: 10.3390/cancers13092234. View

13.

Huang S, Li G, Zhou X, Chen X, Yao Y, Zhang X . Identification of an Immune Score-Based Gene Panel with Prognostic Power for Oral Squamous Cell Carcinoma. Med Sci Monit. 2020; 26:e922854. PMC: 7305786. DOI: 10.12659/MSM.922854. View

14.

Han X, Chen J, Wang J, Xu J, Liu Y . TTN mutations predict a poor prognosis in patients with thyroid cancer. Biosci Rep. 2022; 42(7). PMC: 9310696. DOI: 10.1042/BSR20221168. View

15.

Li Y, Zheng J, Wang E, Gong C, Lan K, Ding X . The m6A reader protein YTHDC2 is a potential biomarker and associated with immune infiltration in head and neck squamous cell carcinoma. PeerJ. 2020; 8:e10385. PMC: 7700739. DOI: 10.7717/peerj.10385. View

16.

Takahashi H, Sakakura K, Ida S, Kawabata-Iwakawa R, Matsuyama T, Tada H . Circulating naïve and effector memory T cells correlate with prognosis in head and neck squamous cell carcinoma. Cancer Sci. 2021; 113(1):53-64. PMC: 8748237. DOI: 10.1111/cas.15195. View

17.

Chen Y, Li Z, Zhou G, Sun Y . An Immune-Related Gene Prognostic Index for Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2020; 27(1):330-341. DOI: 10.1158/1078-0432.CCR-20-2166. View

18.

Siegel R, Miller K, Fuchs H, Jemal A . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. DOI: 10.3322/caac.21708. View

19.

Peng Z, Wang Y, Wang Y, Jiang S, Fan R, Zhang H . Application of radiomics and machine learning in head and neck cancers. Int J Biol Sci. 2021; 17(2):475-486. PMC: 7893590. DOI: 10.7150/ijbs.55716. View

20.

Zhu W, Ye Z, Chen L, Liang H, Cai Q . A pyroptosis-related lncRNA signature predicts prognosis and immune microenvironment in head and neck squamous cell carcinoma. Int Immunopharmacol. 2021; 101(Pt B):108268. DOI: 10.1016/j.intimp.2021.108268. View