Downregulated expression of hsa_circ_0037515 and hsa_circ_0037516 as novel biomarkers for non-small cell lung cancer.

Circular RNAs (circRNAs) represent a class of endogenous non-coding RNAs. Recently, it has been reported that circRNAs might serve as novel potential biomarkers for the diagnosis of cancer, including non-small cell lung cancer (NSCLC). Mutations in the ATP binding cassette subfamily A member 3 (ABCA3) have been increasingly associated with lung disease; however, roles for circRNAs at the ABCA3 locus have not been identified. To characterize novel biomarkers in NSCLC, a bioinformatics platform was used to select circRNAs within the ABCA3 gene. Divergent primers were designed for hsa_circ_0037515 and hsa_circ_0037516, and the PCR products were sequenced to verify their existence in lung tissue. To evaluate diagnostic potential, expression levels of hsa_circ_0037515, hsa_circ_0037516, and ABCA3 were measured by quantitative reverse transcription-polymerase chain reaction; differences in expression levels were analyzed using the paired t-test, and receiver operating characteristic (ROC) curves were established. Our results demonstrate that ABCA3 mRNA, hsa_circ_0037515, and hsa_circ_0037516 are significantly downregulated in 61 paired samples of NSCLC compared to adjacent lung tissues (P < 0.01), and that the areas under the ROC curves for the two circRNAs (0.81 and 0.82, respectively) are indicative of diagnostic value. Furthermore, the significance was improved by considering the two circRNAs in combination (area under the ROC curve, 0.90). Our results suggest that hsa_circ_0037515 and hsa_circ_0037516 serve as novel potential biomarkers for the diagnosis of NSCLC. AJTR