MicroRNA Expression Ratio Is Predictive of Head and Neck Squamous Cell Carcinoma

Abstract

Purpose: The involvement of microRNAs in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated. We sought to identify microRNAs altered in head and neck squamous cell carcinoma (HNSCC) and to determine whether microRNA expression is predictive of disease. Experimental Design: RNA isolated from fresh-frozen primary tumors, fresh-frozen nondiseased head and neck epithelial tissues, and HNSCC cell lines was profiled for the expression of 662 microRNAs by microarray. The microRNAs that were both differentially expressed on the array and by quantitative reverse transcription-PCR were subsequently validated by quantitative reverse transcription-PCR using a total of 99 HNSCC samples and 14 normal epithelia. Results: A marked difference in microRNA expression pattern was observed between tumors and cell lines. Eighteen microRNAs were significantly altered in their expression between normal tissues and tumors. Four of these microRNAs were validated in the larger sample series, and each showed significant differential expression (P < 0.0001). Furthermore, an expression ratio of miR-221:miR-375 showed a high sensitivity (0.92) and specificity (0.93) for disease prediction. Conclusions: These data suggest that cultured tumor cell lines are inappropriate for microRNA biomarker identification and that the pattern of microRNA expression in primary head and neck tissues is reflective of disease status, with certain microRNAs exhibiting strong predictive potential. These results indicate that miR-221 and miR-375 should be evaluated further as diagnostic biomarkers because they may hold utility in defining broadly responsive prevention and treatment strategies for HNSCC.Head and neck squamous cell carcinoma (HNSCC) includes carcinomas arising from the epithelium of the oral cavity, pharynx, and larynx, and is the sixth most common malignancy worldwide (1). The major risk factors for the disease are tobacco and alcohol use, and human papillomavirus infection (2 -4). Despite advances in detection, as well as surgical and chemotherapeutic treatments over recent decades, the 5-year survival rate for HNSCC has remained around

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“…It was recently published that the ratio of miR-221 to miR-375 was predictive for the outcome of head and neck squamous cell carcinoma (25). In our analysis, we found a consistent downregulation of miR-221 and an upregulation of miR-375, whereas the situation was reversed in the head and neck squamous cell carcinoma study.…”

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MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2

“…Until very recently, miR-375 has been found to be deregulated in some malignancies, including live tumor with β-catenin mutation, head and neck squamous cell carcinoma and pancreatic adenocarcinomas [26][27][28][29], whereas little is known about the molecular targets of miR-375 in these cancer. To our knowledge, JAK2 may be the first identified target gene that is involved in the regulation of carcinogenesis by miR-375.…”