title: Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum.
abstract: Pemetrexed combined with platinum is a first-line therapy used to treat patients with advanced non-small cell lung cancer (NSCLC) that exhibit negative or unknown epidermal growth factor receptor (EGFR) mutational status or anaplastic lymphoma kinase (ALK) rearrangements. Lung adenocarcinoma (LAC) is the primary type of NSCLC. In order to prevent overtreatment, it is necessary to identify patients with LAC who may not benefit from certain chemotherapies. Patients recruited in the present study (n=129) were diagnosed with advanced LAC and received first-line pemetrexed and platinum-based chemotherapy. A microRNA (miR) microarray was used to screen the plasma miR expression profiles in a screening set of eight patients prior to and following treatment. Specifically, plasma miR-25, miR-21, miR-27b, miR-326, miR-483-5p and miR-920 were selected for reverse transcription-quantitative polymerase chain reaction analysis in a training set (n=44) prior to treatment. The screening and training set patients were all non-smokers with no prior history of serious or chronic disease. The ∆∆Cq values of these miRs were compared between the group that showed benefit from pemetrexed and platinum treatment and the group that did not. Consequently, the ∆∆Cq values of miR-25, miR-21, miR-27b and miR-326 were further determined in a validation set (n=77). The results of the present study demonstrate that plasma expression levels of miR-25, miR-21, miR-27b and miR-326, in the training and validation sets prior to treatment, were significantly different between the benefit and non-benefit groups (P≤0.001). The expression of miR-25, miR-21, miR-27b and miR-326 was upregulated in the non-benefit group and this elevation was positively correlated with decreased progression-free survival (PFS; P≤0.001). In addition, the predictive power of each miR was evaluated through receiver operating characteristic curves, in which miR-25 exhibited the highest degree of accuracy (area under the curve, 0.926; 95% confidence interval, 0.881-0.971). These results indicate that overexpression of plasma miR-25, miR-21, miR-27b and miR-326, prior to treatment, in patients with advanced LAC is predictive of non-benefit from first-line pemetrexed and platinum-based chemotherapy, and is associated with decreased PFS. Among these four miRs, miR-25 exhibited the highest degree of accuracy in predicting insensitivity, suggesting it is the most promising biomarker.
authors.affiliation: Department of Medical Oncology, Jiangsu Cancer Institute and Hospital, Nanjing, Jiangsu 210002, P.R. China; School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Key Laboratories of Enteric Pathogenic Microbiology, Ministry of Health, Microbiological Laboratory, Jiangsu Center for Disease Prevention and Control, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Research Center of Clinical Oncology, Jiangsu Cancer Institute and Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Jiangsu Cancer Institute and Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Meiqi
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Jiangsu Cancer Institute and Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Feng
authors.affiliation: School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China; Department of Medical Oncology, Jinling Hospital, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Longbang
authors.initials: L
authors.lastname: Chen
keywords: advanced lung adenocarcinoma; circulating microRNA; pemetrexed; platinum; predictive markers