Identification and validation of potential long non‑coding RNA biomarkers in predicting survival of patients with head and neck squamous cell carcinoma

Li,Junyu; Li,Yuehua; Wu,Xiaoping; Li,Ying

doi:10.3892/ol.2019.10261

Identification and validation of potential long non‑coding RNA biomarkers in predicting survival of patients with head and neck squamous cell carcinoma

Authors:
- Junyu Li
- Yuehua Li
- Xiaoping Wu
- Ying Li
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Affiliations: Department of Radiotherapy, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China, Department of Medical Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China
Published online on: April 17, 2019 https://doi.org/10.3892/ol.2019.10261
Pages: 5642-5652
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNAs (lncRNAs) are frequently dysregulated in cancer and their aberrant expression has been associated with cancer diagnosis and prognosis, which suggests that they may be promising molecular biomarkers. However, understanding of the expression pattern of lncRNAs and their prognostic roles in head and neck squamous cell carcinoma (HNSCC) is relatively limited. In the current study, the prognostic value of lncRNA expression profiles in predicting the OS of patients with HNSCC was investigated by integrating clinical and profiling data from The Cancer Genome Atlas. A total of ten lncRNAs closely associated with the prognosis of patients with HNSCC were identified and may serve as novel biomarkers. This 10‑lncRNA signature was used to classify patients into 2 groups with significantly different overall survival (OS) times (median OS time, 1.65 vs. 13.04 years; P<0.0001). This lncRNA signature was validated in an independent testing cohort. The results of multivariable Cox regression and stratification analyses revealed that the prognostic value of the 10‑lncRNA signature was independent of other clinical and pathological factors for the survival of patients with HNSCC. Functional analysis demonstrated that lncRNA expression‑based risk scoring may reflect the basic status of the immune response in the tumor microenvironment. The presented study demonstrated the value of a lncRNA signature as a potential biomarker to improve the clinical prognosis of patients with HNSCC.

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1	Feng Z, Xu QS, Qin LZ, Li H, Huang X, Su M and Han Z: Second primary cancer after index head and neck squamous cell carcinoma in Northern China. Oral Surg Oral Med Oral Pathol Oral Radiol. 123:95–102. 2017. View Article : Google Scholar : PubMed/NCBI
2	Pulte D and Brenner H: Changes in survival in head and neck cancers in the late 20th and early 21st century: A period analysis. Oncologist. 15:994–1001. 2010. View Article : Google Scholar : PubMed/NCBI
3	Grégoire V, Lefebvre JL, Licitra L and Felip E; EHNS-ESMO-ESTRO Guidelines Working Group, : Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 21 (Suppl 5):v184–v186. 2010. View Article : Google Scholar : PubMed/NCBI
4	ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, et al: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 447:799–816. 2007. View Article : Google Scholar : PubMed/NCBI
5	Hangauer MJ, Vaughn IW and McManus MT: Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet. 9:e10035692013. View Article : Google Scholar : PubMed/NCBI
6	Zhang H, Chen Z, Wang X, Huang Z, He Z and Chen Y: Long non-coding RNA: A new player in cancer. J Hematol Oncol. 6:372013. View Article : Google Scholar : PubMed/NCBI
7	Zhou M, Zhang Z, Zhao H, Bao S, Cheng L and Sun J: An immune-related six-lncRNA signature to improve prognosis prediction of glioblastoma multiforme. Mol Neurobiol. 55:3684–3697. 2018.PubMed/NCBI
8	Zhou M, Zhao H, Xu W, Bao S, Cheng L and Sun J: Discovery and validation of immune-associated long non-coding RNA biomarkers associated with clinically molecular subtype and prognosis in diffuse large B cell lymphoma. Mol Cancer. 16:162017. View Article : Google Scholar : PubMed/NCBI
9	Zhou M, Zhang Z, Zhao H, Bao S and Sun J: A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma. BMC Cancer. 18:392018. View Article : Google Scholar : PubMed/NCBI
10	Zhou M, Zhao H, Wang X, Sun J and Su J: Analysis of long noncoding RNAs highlights region-specific altered expression patterns and diagnostic roles in Alzheimer's disease. Brief Bioinform. Apr 17–2018.Doi: 10.1093/bib/bby021.
11	Guan GF, Zhang DJ, Wen LJ, Xin D, Liu Y, Yu DJ, Su K, Zhu L, Guo YY and Wang K: Overexpression of lncRNA H19/miR-675 promotes tumorigenesis in head and neck squamous cell carcinoma. Int J Med Sci. 13:914–922. 2016. View Article : Google Scholar : PubMed/NCBI
12	Wu B, Liu J, Wang B, Liao X, Cui Z and Ding N: Association on polymorphisms in LncRNA HOTAIR and susceptibility to HNSCC in Chinese population. Eur Rev Med Pharmacol Sci. 22:702–706. 2018.PubMed/NCBI
13	Yu J, Liu Y, Guo C, Zhang S, Gong Z, Tang Y, Yang L, He Y, Lian Y, Li X, et al: Upregulated long non-coding RNA LINC00152 expression is associated with progression and poor prognosis of tongue squamous cell carcinoma. J Cancer. 8:523–530. 2017. View Article : Google Scholar : PubMed/NCBI
14	Li J, Han L, Roebuck P, Diao L, Liu L, Yuan Y, Weinstein JN and Liang H: TANRIC: An interactive open platform to explore the function of lncRNAs in cancer. Cancer Res. 75:3728–3737. 2015. View Article : Google Scholar : PubMed/NCBI
15	Zhou M, Guo M, He D, Wang X, Cui Y, Yang H, Hao D and Sun J: A potential signature of eight long non-coding RNAs predicts survival in patients with non-small cell lung cancer. J Transl Med. 13:2312015. View Article : Google Scholar : PubMed/NCBI
16	Zhou M, Sun Y, Sun Y, Xu W, Zhang Z, Zhao H, Zhong Z and Sun J: Comprehensive analysis of lncRNA expression profiles reveals a novel lncRNA signature to discriminate nonequivalent outcomes in patients with ovarian cancer. Oncotarget. 7:32433–32448. 2016.PubMed/NCBI
17	Zhou M, Zhao H, Wang Z, Cheng L, Yang L, Shi H, Yang H and Sun J: Identification and validation of potential prognostic lncRNA biomarkers for predicting survival in patients with multiple myeloma. J Exp Clin Cancer Res. 34:1022015. View Article : Google Scholar : PubMed/NCBI
18	Blanche P, Dartigues JF and Jacqmin-Gadda H: Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med. 32:5381–5397. 2013. View Article : Google Scholar : PubMed/NCBI
19	Moreno-Betancur M, Sadaoui H, Piffaretti C and Rey G: Survival analysis with multiple causes of death: Extending the competing risks model. Epidemiology. 28:12–19. 2017. View Article : Google Scholar : PubMed/NCBI
20	Cancer Genome Atlas Network: Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 517:576–582. 2015. View Article : Google Scholar : PubMed/NCBI
21	Chung CH, Parker JS, Karaca G, Wu J, Funkhouser WK, Moore D, Butterfoss D, Xiang D, Zanation A, Yin X, et al: Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell. 5:489–500. 2004. View Article : Google Scholar : PubMed/NCBI
22	Feldman R, Gatalica Z, Knezetic J, Reddy S, Nathan CA, Javadi N and Teknos T: Molecular profiling of head and neck squamous cell carcinoma. Head Neck. 38 (Suppl 1):E1625–E1638. 2016. View Article : Google Scholar : PubMed/NCBI
23	Ramdas L, Giri U, Ashorn CL, Coombes KR, El-Naggar A, Ang KK and Story MD: miRNA expression profiles in head and neck squamous cell carcinoma and adjacent normal tissue. Head Neck. 31:642–654. 2009. View Article : Google Scholar : PubMed/NCBI
24	Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, Perez-Ordonez B, Jurisica I, O'Sullivan B, Waldron J, et al: Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res. 16:1129–1139. 2010. View Article : Google Scholar : PubMed/NCBI
25	Cao W, Liu JN, Liu Z, Wang X, Han ZG, Ji T, Chen WT and Zou X: A three-lncRNA signature derived from the Atlas of ncRNA in cancer (TANRIC) database predicts the survival of patients with head and neck squamous cell carcinoma. Oral Oncol. 65:94–101. 2017. View Article : Google Scholar : PubMed/NCBI
26	Zhang ZL, Zhao LJ, Chai L, Zhou SH, Wang F, Wei Y, Xu YP and Zhao P: Seven LncRNA-mRNA based risk score predicts the survival of head and neck squamous cell carcinoma. Sci Rep. 7:3092017. View Article : Google Scholar : PubMed/NCBI
27	Behrens J: The role of cell adhesion molecules in cancer invasion and metastasis. Breast Cancer Res Treat. 24:175–184. 1993. View Article : Google Scholar : PubMed/NCBI
28	Howell GM and Grandis JR: Molecular mediators of metastasis in head and neck squamous cell carcinoma. Head Neck. 27:710–717. 2005. View Article : Google Scholar : PubMed/NCBI
29	Varilla V, Atienza J and Dasanu CA: Immune alterations and immunotherapy prospects in head and neck cancer. Expert Opin Biol Ther. 13:1241–1256. 2013. View Article : Google Scholar : PubMed/NCBI
30	Economopoulou P, Perisanidis C, Giotakis EI and Psyrri A: The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): Anti-tumor immunity and clinical applications. Ann Transl Med. 4:1732016. View Article : Google Scholar : PubMed/NCBI