Expression of Long Non-coding RNA in Oral Squamous Cell Carcinoma and Its Implication in Response to Radiation Therapy.

Background Concurrent systemic therapy with radiotherapy (RT) has been used as one of the treatment modalities in early and locally advanced tumors of the oral cavity. However, not all patients respond to radiotherapy equally because of the heterogeneity in tumor microenvironments, where long non-coding RNAs(lncRNAs) seem to have a role. Objective The primary objective of this study is to assess the over expression of five lncRNAs, namely, Opa interacting protein 5 (OIP5), colon cancer-associated transcript-1 (CCAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), maternally expressed gene 3 (MEG3), and urothelial cancer associated 1 (UCA1) in the tissue and plasma of oral squamous cell carcinoma (OSCC) patients and correlation of this expression and response to radiation therapy. The secondary objective was to assess the feasibility of plasma lncRNA expression as a biomarker for response assessment. Materials and methods  This is a prospective study conducted in the Department of Surgical Oncology and the Multidisciplinary Research Unit of Government Rajaji Hospital, Madurai. From 41 OSCC patients planned for radical RT, a biopsy from the primary lesion (41 test tissue samples) and a plasma sample (41 test plasma samples) were collected before RT for the detection of lncRNAs OIP5, CCAT1, MALAT1, MEG3 and UCA1, and their overexpression was compared with the control value derived from tissue samples of normal healthy oral mucosa of these OSCC patients (41 control tissue samples) and plasma samples taken from 41 healthy volunteers (41 control plasma samples), respectively. Long non-coding RNA expression was detected using the reverse transcription polymerase chain reaction (RT-PCR) technique. A fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan was performed before and three months after treatment for response assessment, and patients were classified based on response into complete responders (CR), partial responders (PR), stable disease (SD), and progressive disease (PD), as per RECIST 1.1 criteria. The differential overexpression of plasma lncRNAs was compared based on response. Statistical analysis was done using SPSS software version 21 (IBM Corp., Armonk, NY, US). The paired t-test and chi-square test were used for statistical significance. Results Among progressive disease (PD) patients, expression of lncRNAs OIP5 (p value 0.018) and CCAT1 (p value 0.016) in the pre-treatment plasma was significantly higher compared to complete responder (CR) patients. Conclusion Preoperative plasma OIP5 and CCAT1 expression are associated with radiotherapy resistance. Their role as a biomarker needs further evaluation.