Langevin SM, Stone RA, Bunker CH, Lyons-Weiler MA, Laframboise WA, Kelly L et al.. MicroRNA-137 promoter methylation is associated with poorer overall survival in patients with squamous cell carcinoma of the head and neck. Cancer 117: 1454-1462

University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, Pennsylvania 15213-1863, USA.
Cancer (Impact Factor: 4.89). 04/2011; 117(7):1454-62. DOI: 10.1002/cncr.25689
Source: PubMed


The overall 5-year survival rate of approximately 60% for head and neck cancer patients has remained essentially unchanged over the past 30 years. MicroRNA-137 (miR-137) plays an essential role in cell-cycle control at the G1/S-phase checkpoint. However, the aberrant miR-137 promoter methylation observed in squamous cell carcinoma of the head and neck (SCCHN) suggests a tumor-specific molecular defect that may contribute to disease progression.
The goal of this study was to assess, in formalin-fixed, paraffin-embedded tumor tissue, the association between miR-137 promoter methylation and survival (both overall and disease free) and with prognostic factors including stage, tumor size, lymph node positivity, tumor grade, and surgical tumor margin positivity.
The promoter methylation status of miR-137 was ascertained by methylation-specific polymerase chain reaction and detected in 11 of 67 SCCHN patients (16.4%), with no significant differences according to site (oral cavity, pharynx, larynx). Methylation of the miR-137 promoter was significantly associated with overall survival (hazard ratio, 3.68; 95% confidence interval, 1.01-13.38) but not with disease-free survival or any of the prognostic factors evaluated.
The results of this study indicate that miR-137 is methylated in tumor tissue from pharyngeal and laryngeal squamous cancers, in addition to oral squamous cell carcinoma, and that miR-137 promoter methylation has potential utility as a prognostic marker for SCCHN.

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    • "Similar to what has been observed in glioblastoma cells, restoration of miR-137 reduced cell proliferation of colon cancer lines HCT116 and RKO [14]. Regulation of miR-137 expression via promoter hypermethylation is perhaps a common mechanism as it was also established in oral cancer, gastric cancer and squamous cell carcinoma of head and neck [15]–[18]. Uveal melanoma is another tumor type affected by miR-137 where its expression is lower in uveal melanoma cell lines when compared to uveal melanocytes. Ectopic expression of miR-137 in melanoma cells induced G1 cell cycle arrest and a decrease in cell growth [19]. "
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    • "The study concluded that salivary miR-31 as a cancer biomarker had greater sensitivity than that using plasma [57]. Langevin et al. found that there were higher miR-137 methylation levels in salivary mouth rinses of HNSCC patients [98], with a follow-up study concluding that patients with higher miR-137 methylation levels were associated with lower survival rates [99]. Given the current low literature base, more research is required to better elucidate the role of salivary miRs in HNSCC diagnostics and prognosis. "
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    • "We found that the promoter region of miR-137 was hypermethylated in GBM as compared with normal brain specimens, which may account, at least in part, for the downregulation of miR-137 in these tumors. Similarly, the downregulation of miR-137 in squamous cell carcinoma of the head and neck, gastric cancer, bladder cancer and colorectal cancer has been also attributed to hypermethylation of pre-miR-137 promoter [27-29]. "
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