Identification of an 8 HPV-related RNA signature as a novel prognostic biomarker for squamous cell carcinoma of the head and neck

被引:4
作者
Mei, Zhang [1 ]
Zhengdong, Luo [2 ]
Shupeng, Liu [3 ]
Xin, Zhang [2 ]
Lei, Wang [4 ]
Wang, Chuanxin [5 ]
机构
[1] Shandong Med Coll, Dept Dent, Jinan, Peoples R China
[2] Shandong Univ, Dept Clin Lab, Qilu Hosp, Jinan, Peoples R China
[3] Yidu Cent Hosp Weifang, Dept Outpatient, Weifang, Peoples R China
[4] Shandong Univ, Dept Orthoped, Qilu Hosp, Jinan, Peoples R China
[5] Shandong Univ, Dept Clin Lab, Hosp 2, 247 Beiyuan St, Jinan, Peoples R China
关键词
biomarkers; head and neck neoplasms; prognosis; HUMAN-PAPILLOMAVIRUS; CANCER; MICRORNA; SURVIVAL; GROWTH; GENE; DIFFERENTIATION; THERAPY; MARKER; LINE;
D O I
10.1097/MD.0000000000036448
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Squamous cell carcinoma of the head and neck (SCCHN) is a commonly detected cancer worldwide. Human papillomavirus (HPV) is emerging as an important risk factor affecting SCCHN prognosis. Therefore, identification of HPV status is essential for effective therapies in SCCHN. The aim of this study was to investigate the prognostic value of HPV-associated RNA biomarkers for SCCHN. The clinical data, survival data, and RNA-seq data of SCCHN were downloaded from The Cancer Genome Atlas database. Before the differential expression analysis, the heterogeneity between the 2 groups (HPV+ vs HPV-) of samples was analyzed using principal component analysis. The differentially expressed genes (DEGs) between HPV+ and HPV- SCCHN samples were analyzed using the R edgeR package. The Gene Ontology functional annotations, including biological process, molecular function and cellular component (CC), and Kyoto Encyclopedia of Genes And Genomes pathways enriched by the DEGs were analyzed using DAVID. The obtained matrix was analyzed by weighed gene coexpression network analysis. A total of 350 significant DEGs were identified through differential analysis, and these DEGs were significantly enriched in functions associated with keratinization, and the pathway of neuroactive ligand-receptor interaction. Moreover, 72 hub genes were identified through weighed gene coexpression network analysis. After the hub genes and DEGs were combined, we obtained 422 union genes, including 65 survival-associated genes. After regression analysis, a HPV-related prognostic model was established, which consisted of 8 genes, including Clorf105, CGA, CHRNA2, CRIP3, CTAG2, ENPP6, NEFH, and RNF212. The obtained regression model could be expressed by an equation as follows: risk score = 0.065 x Clorf105 + 0.012 x CGA + 0.01 x CHRNA2 + 0.047 x CRIP3 + 0.043 x CTAG2-0.034 x ENPP6 - 0.003 x NEFH - 0.068 x RNF212. CGA interacted with 3 drugs, and CHRNA2 interacted with 11 drugs. We have identified an 8 HPV-RNA signature associated with the prognosis of SCCHN patients. Such prognostic model might serve as possible candidate biomarker and therapeutic target for SCCHN.
引用
收藏
页数:9
相关论文
共 42 条
[1]   Alteration of proto-oncogenes during apoptosis in the oral squamous cell carcinoma cell line, SAS, induced by staurosporine [J].
Abiko, Y ;
Arai, J ;
Mitamura, J ;
Kaku, T .
CANCER LETTERS, 1997, 118 (01) :101-107
[2]   Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer [J].
Ang, K. Kian ;
Harris, Jonathan ;
Wheeler, Richard ;
Weber, Randal ;
Rosenthal, David I. ;
Nguyen-Tan, Phuc Felix ;
Westra, William H. ;
Chung, Christine H. ;
Jordan, Richard C. ;
Lu, Charles ;
Kim, Harold ;
Axelrod, Rita ;
Silverman, C. Craig ;
Redmond, Kevin P. ;
Gillison, Maura L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (01) :24-35
[3]   Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer [J].
Bernier, J ;
Domenge, C ;
Ozsahin, M ;
Matuszewska, K ;
Lefèbvre, JL ;
Greiner, RH ;
Giralt, J ;
Maingon, P ;
Rolland, F ;
Bolla, M ;
Cognetti, F ;
Bourhis, J ;
Kirkpatrick, A ;
van Glabbeke, M .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (19) :1945-1952
[4]  
Bièche I, 2001, CANCER RES, V61, P1652
[5]  
Cardesa A, 2011, ACTA DERMATOVEN ALP, V20, P161
[6]   Implication of downregulation and prospective pathway signaling of microRNA-375 in lung squamous cell carcinoma [J].
Chen, Wen-jie ;
Gan, Ting-qing ;
Qin, Hui ;
Huan, Su-ning ;
Yang, Li-hua ;
Fang, Ye-ying ;
Li, Zu-yun ;
Pan, Lin-jiang ;
Chen, Gang .
PATHOLOGY RESEARCH AND PRACTICE, 2017, 213 (04) :364-372
[7]   HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: Utility of microscopic features in predicting patient outcome [J].
Chernock R.D. ;
El-Mofty S.K. ;
Thorstad W.L. ;
Parvin C.A. ;
Lewis Jr J.S. .
Head and Neck Pathology, 2009, 3 (3) :186-194
[8]   Morphologic Features of Conventional Squamous Cell Carcinoma of the Oropharynx: 'Keratinizing' and 'Nonkeratinizing' Histologic Types as the Basis for a Consistent Classification System [J].
Chernock R.D. .
Head and Neck Pathology, 2012, 6 (Suppl 1) :41-47
[9]   Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].
Chin, L. ;
Meyerson, M. ;
Aldape, K. ;
Bigner, D. ;
Mikkelsen, T. ;
VandenBerg, S. ;
Kahn, A. ;
Penny, R. ;
Ferguson, M. L. ;
Gerhard, D. S. ;
Getz, G. ;
Brennan, C. ;
Taylor, B. S. ;
Winckler, W. ;
Park, P. ;
Ladanyi, M. ;
Hoadley, K. A. ;
Verhaak, R. G. W. ;
Hayes, D. N. ;
Spellman, Paul T. ;
Absher, D. ;
Weir, B. A. ;
Ding, L. ;
Wheeler, D. ;
Lawrence, M. S. ;
Cibulskis, K. ;
Mardis, E. ;
Zhang, Jinghui ;
Wilson, R. K. ;
Donehower, L. ;
Wheeler, D. A. ;
Purdom, E. ;
Wallis, J. ;
Laird, P. W. ;
Herman, J. G. ;
Schuebel, K. E. ;
Weisenberger, D. J. ;
Baylin, S. B. ;
Schultz, N. ;
Yao, Jun ;
Wiedemeyer, R. ;
Weinstein, J. ;
Sander, C. ;
Gibbs, R. A. ;
Gray, J. ;
Kucherlapati, R. ;
Lander, E. S. ;
Myers, R. M. ;
Perou, C. M. ;
McLendon, Roger .
NATURE, 2008, 455 (7216) :1061-1068
[10]   Association of Keratinization With 5-Year Disease-Specific Survival in Oropharyngeal Squamous Cell Carcinoma [J].
Cooper, Timothy ;
Biron, Vincent L. ;
Ben Adam ;
Klimowicz, Alexander C. ;
Puttagunta, Lakshmi ;
Seikaly, Hadi .
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY, 2015, 141 (03) :250-256