title: miR-21 and miR-375 microRNAs as candidate diagnostic biomarkers in squamous cell carcinoma of the larynx: association with patient survival.
abstract: The dismal outcome of laryngeal squamous cell carcinoma (SCC) patients highlights the need for novel prognostic biomarkers. The involvement of microRNAs in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated. We sought to identify microRNAs that exhibit altered expression in laryngeal SCC and to determine whether microRNA (miRNA) expression is predictive of disease progression and/or patient survival. The expression of two miRNAs, miR-21 and miR-375, was evaluated using total RNA isolated from freshly-frozen primary tumors and non-cancerous laryngeal squamous epithelial tissues and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. We further analyzed the association between the expression of miRNAs and the clinicopathological features. A marked difference in the microRNA expression pattern was observed between tumors and non-cancerous tissue. MiR-21 and miR-375 were expressed at higher and lower levels, respectively, in the laryngeal SCC samples, compared to the normal samples (p < 0.01 and p < 0.001, respectively). There was no correlation between characteristics such as age, sex, clinical stage, and alcohol use, and the expression level of mir-21. The relative expression of mir-375 in laryngeal SCC was shown to be associated with localization of the tumor in these patients (p = 0.037) and with alcohol use (p < 0.05). Patients with high miR-21 or low miR-375 expression in tumor tissues had poorer prognoses compared to patients with lower miR-21 or higher miR-375 expression. Furthermore, the miR-21/miR-375 expression ratio was highly sensitive (0.94) and specific (0.94) for disease prediction. These data suggest that the pattern of microRNA expression in primary laryngeal SCC tissues is reflective of the disease status and that miR-21 and miR-375 expression levels, in particular, may serve as potential biomarkers with applications in the clinical setting.
authors.affiliation: Department of Otolaryngology, Gongli Hospita Pudong New Area, Miaopu Road 219, Shanghai 200135, China.
authors.forename: An
authors.initials: A
authors.lastname: Hu
authors.affiliation: Department of Gerontology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Kongjiang Road 1665, Shanghai 200092, China.
authors.forename: Jing-Juan
authors.initials: JJ
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology, Gongli Hospita Pudong New Area, Miaopu Road 219, Shanghai 200135, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine Pudong New Area, Dongfang Road 1630, Shanghai 200127, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Jin
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine Pudong New Area, Dongfang Road 1630, Shanghai 200127, China.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Li
authors.affiliation: Joint Molecular Rheumatology Laboratory of The Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shandong(M) Road 145, Shanghai 200001, China.
authors.forename: Yuan-Jia
authors.initials: YJ
authors.lastname: Tang
authors.affiliation: Joint Molecular Rheumatology Laboratory of The Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shandong(M) Road 145, Shanghai 200001, China.
authors.forename: Xin-Fang
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Joint Molecular Rheumatology Laboratory of The Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shandong(M) Road 145, Shanghai 200001, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Cui
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Huashan Hospital, Shanghai Fudan University School of Medicine Wurumuqi Road 12, Shanghai 200040, China.
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Sun
keywords: Laryngeal squamous cell carcinoma; biomarker; microRNA; prognosis