Abstract 5228: Characterization of miR-21 as a potential circulating biomarker for osteosarcoma

Abstract

Abstract MicroRNAs (miRNAs) are a class of small noncoding RNAs that are implicated in various important biological processes by regulation of gene expression. Aberrant miRNA expression is suggested to be associated with various human disorders including cancer. In this study, we studied if miRNAs can be used as biomarkers in osteosarcoma (OS). OS is the most common malignant bone tumor in children and young adults. Despite the use of surgery and multi-agent chemotherapy, OS patients who respond poorly towards chemotherapy or develop relapses have a dismal outcome. Thus, it is of clinical significance if a biomarker approach can be developed to monitor tumor burden and detect early relapses in the patients, so that they can be treated as early as possible to improve the survival. To achieve this goal, we performed miRNA profiling on a cohort of OS plasma samples collected from the Texas Children's Hospital. miR-21 and other miRNAs were identified to be elevated in OS patients relative to a group of healthy controls. Circulating miR-21 has been detected in other types of cancer and in the tumor it is known to negatively regulate tumor suppressor genes involved in proliferation, apoptosis and invasion; however, its role in OS is still unclear. Hence, we first validated that miR-21 was elevated in a set of independent osteosarcoma plasma samples but not in the control samples. Using serial plasma samples from a group of patients, we found that the circulating miR-21 level was lower in the posttreatment plasma samples than in the pretreatment samples. These results suggest that circulating miR-21 may correlate with tumor burden of the patients. In addition, miR-21 was expressed in many OS tumors as detected by in situ hybridization on an OS tissue microarray. When tested on two OS cell lines, miR-21was significantly increased in the culture media between 24 and 48 hours after plating in a cell number dependent manner, suggesting that miR-21 could be released from the tumor cells. Taken together, our results suggest that miR-21 is expressed in OS and its level in plasma may reflect tumor burden in OS patients. Citation Format: Manjula Nakka, Yiting Li, Colin McGee, Ching Lau, Tsz Kwong Man. Characterization of miR-21 as a potential circulating biomarker for osteosarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5228. doi:10.1158/1538-7445.AM2014-5228