Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 12, Pages 8280-8291Publisher
WILEY
DOI: 10.1111/jcmm.14702
Keywords
biomarker; hypopharyngeal cancer; miRNA; score; signature; survival
Categories
Funding
- Shandong Province
- Department of Science & Technology of Shandong Province [2017GSF8166, 2019GSF108003, 2019GSF108097]
- Administration of Science & Technology of Qingdao [17-3-3-9-nsh]
- Horizontal project of Shandong University [11671714]
- Science Foundation of Qilu Hospital of Shandong University [2016QLQN38]
- Department of Health of Shandong Province [2016WS0344, 2016WSB20023]
- National Natural Science Foundation of China [81700890]
- Natural Science Foundation of Shandong Province [ZR2017BH115]
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Since the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) remains poor, identification of miRNA as a potential prognostic biomarker for HSCC may help improve personalized therapy. In the 2 cohorts with a total of 511 patients with HSCC (discovery: N = 372 and validation: N = 139) after post-operative radiotherapy, we used miRNA microarray and qRT-PCR to screen out the significant miRNAs which might predict survival. Associations of miRNAs and the signature score of these miRNAs with survival were performed by Kaplan-Meier survival analysis and multivariate Cox hazard model. Among 9 candidate, miRNAs, miR-200a-3p, miR-30b-5p, miR-3161, miR-3605-5p, miR-378b and miR-4451 were up-regulated, while miR-200c-3p, miR-429 and miR-4701 were down-regulated after validation. Moreover, the patients with high expression of miR-200a-3p, miR-30b-5p and miR-4451 had significantly worse overall survival (OS) and disease-specific survival (DSS) than did those with low expression (log-rank P < .05). Patients with a high-risk score had significant worse OS and DSS than those with low-risk score. Finally, after adjusting for other important prognostic confounders, patients with high expression of miR-200a-3p, miR-30b-5p and miR-4451 had significantly high risk of overall death and death owing to HSCC and patients with a high-risk score has approximately 2-fold increased risk in overall death and death owing to HSCC compared with those with a low-risk score. These findings indicated that the 3-miRNA-based signature may be a novel independent prognostic biomarker for patients given surgery and post-operative radiotherapy, supporting that these miRNAs may jointly predict survival of HSCC.
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