Title : Role of micro RNAs (miR-22, miR-301a and miR-584) in chemoresistance of osteosarcoma- an observational study(MICRO)
Abstract:
Osteosarcoma is one of the most common primary malignant sarcomas of musculo-skeletal system, with bimodal age distribution. There has been a paucity in improvement of disease-free survival of osteosarcoma patients in recent times owing to development of chemoresistance to chemotherapeutic agents. Hence, this study aims to investigate the possible role of microRNAs in the development of chemoresistance for their potential diagnostic and therapeutic applications.
Study Design: An observational study done on 13 diagnosed cases of Osteosarcoma by histopathological analysis. Tumor tissue were taken at time of diagnostic biopsy and tumor resection, after course of three cycles of neoadjuvant chemotherapy comprising of two drugs i.e., Doxorubicin and Cisplatin. Tumor tissue were stored in RNAlater solution at -80°C which were later processed and analysed for targeted MicroRNAs by RT-qPCR and patients were divided into two groups of good and poor responders to chemotherapy based upon necrosis seen in tumor resection specimen on histopathological analysis. Fold change was compared between two groups for each microRNA using unpaired t – test and graphs were plotted using software Graphpad prism 9.0.
Results: In this current study, the patients conformed with the published data with regards to age, sex, and site of origin. Based upon histopathological analysis, out of total of 13 patients assessed, only 3 were good responders while the rest 10 patients were poor responders. A difference in fold change between good and poor responders was seen such that miR-22-3p is increased in poor responders while miR-301a-3p and miR-584 are increased in good responders. On analysing the fold change between two groups of good and poor responders by Unpaired t-test for all 3 microRNAs individually, the results were not significant as p values were more than 0.05.
Conclusion: Our study had a unique study design where tumor tissues were retrieved in vivo, from the human body during the course of NACT and then tested for microRNA expression. Relative expression of mir-584 revealed upregulation of miR-584 in good responders as compared to poor responders (fold change 5.9813) which is in concurrence with previous literature. This microRNA can be potentially used as a biomarker in the prognosis of osteosarcoma as well as can be targeted to modulate gene expression and treat chemoresistance in osteosarcoma. However, the small sample size of our study is a limitation and future studies must be done on a larger sample size.
