IMR Press / FBL / Volume 27 / Issue 1 / DOI: 10.31083/j.fbl2701002
Open Access Original Research
Identification of differentially expressed genes and pathways for risk stratification in HPV-associated cancers governing different anatomical sites
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1 Interdisciplinary Program of Genomic Science, Pusan National University, 50612 Yangsan, Republic of Korea
2 Department of Otolaryngology, Ajou University School of Medicine, 16499 Suwon, Republic of Korea
3 Department of Pathology, Ajou University School of Medicine, 16499 Suwon, Republic of Korea
4 Department of Anatomy, School of Medicine, Pusan National University, 50612 Yangsan, Republic of Korea
5 Department of Biomedical Informatics, School of Medicine, Pusan National University, 50612 Yangsan, Republic of Korea
6 Department of Biomedical Sciences, Ajou University Graduate School of Medicine, 16499 Suwon, Republic of Korea
*Correspondence: yunhak10510@pusan.ac.kr (Yun Hak Kim); manup1377@gmail.com (Jeon Yeob Jang)
These authors contributed equally.
Academic Editor: Alexandros G. Georgakilas
Front. Biosci. (Landmark Ed) 2022, 27(1), 2; https://doi.org/10.31083/j.fbl2701002
Submitted: 8 July 2021 | Revised: 7 December 2021 | Accepted: 17 December 2021 | Published: 4 January 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Human papillomavirus (HPV) is the major cause of cervical cancer (CC) etiology; its contribution to head and neck cancer (HNC) incidence is steadily increasing. As individual patients’ response to the treatment of HPV-associated cancer is variable, there is a pressing need for the identification of biomarkers for risk stratification that can help determine the intensity of treatment. Methods: We have previously reported a novel prognostic and predictive indicator (HPPI) scoring system in HPV-associated cancers regardless of anatomical location by analyzing The Cancer Genome Atlas and Gene Expression Omnibus databases. In the present study, we comprehensively investigated the association of group-specific expression patterns of common differentially expressed genes (DEGs) between high- and low-risk groups in HPV-associated CC and HNC, identifying molecular biomarkers and pathways for risk stratification. Results: Among the 174 identified DEGs, the expression of genes associated with extracellular matrix (ECM)-receptor interaction pathway (ITGA5, ITGB1, LAMB1, and LAMC1) was increased in high-risk groups in both HPV-associated CC and HNC, while the expression of genes associated with T-cell immunity (CD3D, CD3E, CD8B, LCK, and ZAP70) was decreased and vice versa. The individual genes showed significant prognostic impact on HPV-associated cancers but not on HPV-negative cancers. The expression levels of identified genes were similar between HPV-negative and HPV-associated high-risk groups with distinct expression patterns only in HPV-associated low-risk groups. Each group of genes showed negative correlations and distinct patterns of immune cell infiltration in tumor microenvironments. Conclusions: These results allowed us to identify molecular biomarkers and pathways for risk stratification in HPV-associated cancers regardless of anatomical location. The identified targets were found to be selectively working in only HPV-associated cancers and not in HPV-negative cancers, indicating the possibility of selective targets governing HPV-infective tumor microenvironments.

Keywords
Human papillomavirus
Risk stratification
Head and neck cancer
Cervical cancer
Prognostic biomarker
Figures
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