Plasma MiRNAs As An Indicator Of Radiosensitivity In Non-small Cell Lung Cancer

Background and PurposeLung cancer is a malignant tumor that causes the highest morbidity and mortality, andthe main pathological type is non-small cell lung cancer (NSCLC). Radiotherapy is animportant treatment strategy for lung cancer. It is estimated that approximately60%–70%ofall the NSCLC patients develop one or more indications for RT. However, radical RT cannoteradiate the tumors, and thus the residual tumors relapse. The local recurrence rate ofadvanced NSCLC after conventional fractionated radiotherapy (CFRT)(60Gy/30F/6W) isup to60%–70%in two years. Radiation resistance is the leading cause of poor efficacy ofRT.MicroRNAs (miRNAs) are a class of evolutionarily conserved, endogenous, small,non-coding RNA, regulating posttranscriptional mRNA expression. MiRNAs play roles inneoplasm development, progression, diagnosis and prognosis in many tumors. Recentstudys revealed that miRNAs are closely related to some important biological processes,such as chemoradiotherapy resistance, cancer stem cell (CSC) properties, andepithelial-mesenchymal transition (EMT). MiRNAs can be an indicator of radiosensitivity innon-small cell lung cancer, due to its tissue specificity, stable expression and quantitativeanalysis.Methods1. Differential gene expression profiles of radiosensitive lung cancer cell line H460andradioresistant cell line H1299were screened from GEO (Gene Expression Omnibus)database. Using bioinformatics to process the data, including tissue specificity analysis,miRNA prediction analysis, GO and pathway analysis, we obtained a miRNAs expressionprofile of radiosensitive and radioresistant NSCLC.2. The expressions of plasma miRNAs in patients receiving pure radiotherapy weredetected by qRT-PCR. According to RECIST1.1evaluation standard and local progression-free survival (PFS), we divided the patients into radiosensitive andradioresistant groups, and then compared miRNAs expression differences between the twogroups.Results1. We screened19differential expressions miRNAs in H460and H1299cell lines. Ofthe19miRNAs,14key ones were related to radioresistance (hsa-miR-1, hsa-miR-1297,hsa-miR-153, hsa-miR-193a-3p, hsa-miR-206, hsa-miR-302e, hsa-miR-328, hsa-miR-372,hsa-miR-495, hsa-miR-520a-3p, hsa-miR-520b, hsa-miR-520d-3p, hsa-miR-520e, andhsa-miR-613), and five were related to radiosensitivity (hsa-let-7c, hsa-miR-137,hsa-miR-203a, hsa-miR-34c-5p, and hsa-miR-98).2. A total of39NSCLC patients were divided into radiosensitive group (CR+PR,18cases) and radioresistant group (SD+PD,21cases). The expressions of hsa-let-7c andhsa-miR-18a were significantly higher in the radiosensitive group than in the radioresistantgroup (P<0.05). Compared with the radiosensitive group, the expressions of hsa-miR-495and hsa-miR-203a hardly changed in the radioresistant group (P>0.05).3. We followed up the patients until March15,2014. Eight patients were censored dueto no progression in disease. The median local PFS was4months (1to9.2months). Theexpressions of hsa-let-7c, hsa-miR-18a, hsa-miR-495and hsa-miR-203a showed nosignificant difference (P>0.05) between the radiosensitive group (>median local PFS,14cases) and the radioresistant group (≤median local PFS,17cases).ConclusionThe expressions of hsa-let-7c and hsa-miR-18a in plasma were positively correlatedwith the short-term effects of radiotherapy, and the miRNAs can be used as a novelindicator of therapeutic effects on NSCLC.