Serum Mirna Signatures Predict Survival Of Nsclc

Purpose Recent findings that human serum contains stably expressed microRNAs (miRNAs) have revealed a great potential of serum miRNA signature as disease fingerprints to predict survival. We used genome-wide serum miRNA expression analysis to investigate the role of serum miRNA in predicting prognosis of NSCLC. Patients and Methods To control disease heterogeneity, we used patients with stage I-IIIa lung adenocarcinoma and squamous cell carcinoma, who were treated with both operation and adjuvant chemotherapies. In the discovery stage, Solexa sequencing followed by individual quantitative RT-PCR (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 30 longer survival patients (alive and mean survival time: 49.54 months) and 30 shorter survival patients (dead and mean survival time: 9.54 months) matched by age, sex and stage. The detected serum miRNAs were then validated in 243 patients (randomly classified into two subgroups: 120 for the training set and 123 for the testing set). Results Eleven serum miRNAs were found to be altered more than 5-fold by Solexa sequencing between “longer survival” and “shorter survival” groups, and have at least 50 copies in either “longer survival” or “shorter survival” groups. We then performed individual qRT-PCR assay to quantify each of the identified miRNAs and the levels of four miRNAs (miR-486, miR-30d, miR-1 and miR-499) were significantly different between the “longer survival” and “shorter survival” groups (P = 0.0002 for miR-486, 4.30 × 10 −7 for miR-30d, 0.001 for miR-1 and 0.0001 for miR-499). From the training set, high serum expression levels of miR-486 (median: 0.795) and miR-30d (median: 0.680), and low serum expression levels of miR-1 (median: 0.675), miR-499 (median: 0.750) were all individually associated with unfavorable survival. When these threshold values were applied to the testing set, comparable log-rank P values and HRs were also observed, respectively. Results for all the 303 samples including the discovery dataset were also similar to those from the training set. Patients with high serum expression levels of risk miRNAs and low serum expression levels of protective miRNAs had significantly lower MSTs (31.30 months for miR-486, 22.37 months for miR-30d, 22.87 months for miR-1 and 23.73 months for miR-499, all versus not reached). In the combined analysis, we found that patients carrying two or more high-risk miRNAs had significantly increased probability of cancer death in a dose-dependent manner (log rank test: P Conclusion The four-miRNA signature from the serum may serve as a non-invasive predictor for the overall survival of NSCLC. 1 2 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3002.