To Study The Role Of Pre-treatment MicroRNA Expression As A Predictor Of Response To Chemoradiation In Locally Advanced Carcinoma Cervix

Abstract

Cervical cancer is the fourth most common cancer worldwide. External beam radiotherapy with concurrent cisplatin followed by brachytherapy is considered standard of care in locally advanced carcinoma cervix, with 50% of patients presenting with recurrence or persistent disease. At present there is no prognostic factor to predict the outcome of disease in locally advanced carcinoma cervix patients treated with standard therapy. MicroRNAs(miRNAs)are small, single stranded noncoding RNA constituting 18-22 nucleotides. It has been shown that miRNAs are differentially expressed (upregulated or downregulated) in many cancer cells. Expression of miRNAs can be used as molecular biomarkers to predict clinical response in locally advanced carcinoma cervix patients. In an observational study, we enrolled 32 patients of locally advanced carcinoma cervix (Stage IB- IVA) after pathological confirmation of biopsy sample from 2017-2018. Expression of six microRNA (miRNA-9 5p, miRNA-31 3p, miRNA-100 5p, miRNA-125a 5p, miRNA-125b-5p, miRNA–200a 5p) in formalin fixed paraffin embedded (FFPE) biopsied tissue were analyzed by real time quantitative reverse transcriptase polymerase chain reaction (RT qPCR). Pre-treatment evaluation of disease status was done with clinical examination and MRI pelvis imaging. All patients received external beam radiotherapy with concurrent chemoradiotherapy followed by brachytherapy as standard treatment. Patients were evaluated for clinical response after 3 months of completion of treatment, with clinical examination and MRI pelvis scan using RECIST 1.1 criteria. Responses were classified as complete response (CR) as disappearance of all disease in response to treatment and Non-response (NR) as patients with partial response, stable or progressive disease. Results were statistically analyzed using Mann Whiney U test to examine significant difference between expression of microRNA between patients with complete clinical response (CR) and those with non-response (NR). Out of total 32 patients, 24 patients (75%) had Complete Response and 8 patients (25%) had Non-Response to standard therapy. Out of six miRNAs, expression of miRNA-100 5p was upregulated in complete responders (CR) and downregulated in Nonresponders (NR), which showed a trend towards statistical significance (p value = 0.05). Other microRNAs (miRNA-9 5p, miRNA-31 3p, miRNA-125a 5p, miRNA-125b 5p, miRNA–200a 5p) showed differential expression in complete responders compared to non-responders but their expression did not reach statistical significance level (p value > 0.05). miRNA-100 5p can serve as a potential molecular biomarker in predicting clinical response to chemoradiation in locally advanced Carcinoma cervix patients. Its role should be further investigated in larger study population.