MicroRNAs MiR-218, MiR-125b, and Let-7g predict prognosis in patients with oral cavity squamous cell carcinoma

Shih-Chi Peng; Chun-Ta Liao; Chien-Hua Peng; Ann-Joy Cheng; Shu-Jen Chen; Chung-Guei Huang; Wen-Ping Hsieh; Tzu-Chen Yen

doi:10.1371/journal.pone.0102403

MicroRNAs MiR-218, MiR-125b, and Let-7g predict prognosis in patients with oral cavity squamous cell carcinoma

PLoS One. 2014 Jul 22;9(7):e102403. doi: 10.1371/journal.pone.0102403. eCollection 2014.

Authors

Shih-Chi Peng¹, Chun-Ta Liao², Chien-Hua Peng³, Ann-Joy Cheng⁴, Shu-Jen Chen⁵, Chung-Guei Huang⁶, Wen-Ping Hsieh⁷, Tzu-Chen Yen⁸

Affiliations

¹ Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.
² Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.; Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.
³ Resource Center for Clinical Research, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.
⁴ Department of Medical Biotechnology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.
⁵ Department of Biomedical Sciences, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.
⁶ Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.
⁷ Institute of Statistics, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
⁸ Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.; Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, R.O.C.

Abstract

MicroRNAs (miRNAs) have a major impact on regulatory networks in human carcinogenesis. In this study, we sought to investigate the prognostic significance of miRNAs in patients with oral cavity squamous cell carcinoma (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and TaqMan MicroRNA assays. The prognostic significance of the miRNA signature identified in the discovery phase was validated by qRT-PCR in a replication set consisting of 141 formalin-fixed, paraffin-embedded (FFPE) samples. We identified a miRNA regulatory network centered on the three hub genes (SP1, MYC, and TP53) that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and let-7g) and their downstream response genes had a concordant prognostic significance on disease-free survival and disease-specific survival rates. In addition, patients with a reduced expression of miR-218, miR-125b, and let-7g have a higher risk of poor outcomes in presence of specific risk factors (p-stage III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have prognostic significance in OSCC patients and may improve prognostic stratification over traditional risk factors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / mortality
Cell Line, Tumor
Disease-Free Survival
Gene Expression
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Kaplan-Meier Estimate
MicroRNAs / genetics
MicroRNAs / metabolism*
Mouth Neoplasms / genetics
Mouth Neoplasms / metabolism*
Mouth Neoplasms / mortality
Multivariate Analysis
Prognosis

Substances

MIRN125 microRNA, human
MIRN218 microRNA, human
MicroRNAs
mirnlet7 microRNA, human

Grants and funding

This work was supported by a grant from Chang Gung Medical Foundation (CMRPG3C0831), and was also partly supported by National Council of Science (99-2628-B-182A-002-MY3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.