Abstract 4411: MiR-130b identified by TCGA miRNA-seq data can predict the radio-sensitivity for patients with HPV-negative oropharyngeal squamous cell carcinoma
Authors: Inoue Hitoshi , Kogashiwa Yasunao , Masataka Hirasaki , Sakai Akihiro , Nakahira Mitsuhiko , Okuda Akihiko , Sugasawa Masashi 
Published: August 2018

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) are associated with an increased radio-sensitivity and a favorable outcome compared to HPV-negative OPSCC. To the contrary, HPV-negative patients lack validated prognostic biomarkers. When surgery is selected in the locally advanced HPV-negative OPSCC, the function after surgery may be impaired. Thus, if there is a biomarker to know whether it is radio-sensitive or not, it is useful for treatment selection. It is therefore important to define prognostic biomarkers in this patient population.

Method: miRNA sequence (miRNA-seq) and mRNA sequence (mRNA-seq) of the Cancer Genome Atlas (TCGA) data includes 520 HNSCC tumors. Of them, we used gene expression data in HPV-negative OPSCC, which have data on the effects of radiation. We compared the results of miRNA-Seq in two groups of radio-sensitive and radio-resistant, and miRNA whose expression was different between radio-sensitive and radio-resistant HPV-negative OPSCC was selected. To estimate the function of the miRNA, we also performed mRNA-seq analysis. Finally, we validated the miRNA related to the outcome of radiotherapy in our clinical cases.

Results: We found that miR-130b is highly expressed in radio-sensitive HPV-negative OPSCC by miRNA-seq. From the mRNA-seq, we identified genes with significantly different expression between radio-resistant and radio-sensitive HPV-negative OPSCC. Clustering analysis and Principal Component Analysis have shown the possibility of discriminating between radio-resistant and radio-sensitive in these gene groups. From the gene ontology (GO) analysis in up regulated genes, we identified GO terms. It is presumed that miR-130b targets several genes related to radio-sensitivity, so it is considered that reduced gene expression in radio-sensitive is related to increased expression of miR130b.

Subsequently, we evaluated the expression of miR-130b in our clinical cases. Values of miR130b &gt; 5.372, determined by ROC curves analysis, were associated with significantly longer progression-free survival (p=0.02, log-rank test). Conclusion: The expression change of genes and high expression of miR-130b in radio-sensitive were found by miRNA-seq and mRNA-seq. Our result suggests that miR-130b has a potential to become a biomarker for the radio-sensitivity of HPV-negative OPSCC. The expression of miR-130b as a biomarker for HPV-negative OPSCC requires further evaluation.

Citation Format: Hitoshi Inoue, Yasunao Kogashiwa, Hirasaki Masataka, Akihiro Sakai, Mitsuhiko Nakahira, Akihiko Okuda, Masashi Sugasawa. MiR-130b identified by TCGA miRNA-seq data can predict the radio-sensitivity for patients with HPV-negative oropharyngeal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4411.