miRNA Expression Signatures of Therapy Response in Squamous Cell Carcinomas

Abstract

Introduction: Squamous cell carcinomas (SCC) are a major subgroup of malignant tumors with a platinum-based first-line systematic chemotherapy. miRNAs play a role in various diseases and modulate therapy response as well. The aim of this study was to identify predictive miRNAs in platinum-treated SCCs. Methods: miRNA expression data of platinum-treated head and neck (HNSC), cervical (CESC) and lung (LUSC) cancer were collected from the TCGA repositories. Treatment response was defined based on presence or absence of disease progression at 18 months. Responder and nonresponder cohorts were compared using Mann–Whitney and Receiver Operating Characteristic tests. Logistic regression was developed to establish a predictive miRNA signature. Significance was set at FDR p = 0.001), hsa-miR-632 (Exp (B): 10.75, p = 0.002), hsa-miR-2355 (Exp (B): 0.48, p = 0.004), hsa-miR-642a (Exp (B): 2.22, p = 0.01), hsa-miR-101-2 (Exp (B): 0.39, p = 0.013) and hsa-miR-6728 (Exp (B): 0.21, p = 0.016). The model using these miRNAs was able to predict chemotherapy resistance with an AUC of 0.897. Conclusions: We performed an analysis of RNA-seq data of squamous cell carcinomas samples and identified significant miRNAs correlated to the response against platinum-based therapy in cervical, head and neck, and lung tumors.

Keywords

• chemotherapy
• cisplatin
• carboplatin
• cancer
• miRNA
• head and neck cancer