P2.01-021 miRNA Deep Sequencing of Early-Stage Lung Cancer Patients to Evaluate the Dynamic Change of Circulating Biomarkers in Response to Surgery

Abstract

Early-stage lung cancer patients have a five-year survival rate greater than 70%, however this benefit is not exploited due to late diagnosis. Moreover, for the early-stage patients eligible to surgical intervention the long-term survival is also reduced by the high risk of relapse following surgery. The identification of circulating biomarkers is an attractive and less invasive way to improve the management of lung cancer patients. MicroRNAs (miRNAs) post-transcriptionally modify gene expression and are thus involved in cancer through controlling different cellular processes. Dysregulation of their expression contributes to lung cancer progression both in tissue samples and in the blood stream (plasma/serum). The aim of our study is to assess a miRNA profile from serum patients to identify circulating biomarkers useful to predict surgery outcome in the early-stage NSCLC patients. 16 early-stage NSCLC patients were enrolled. Serum samples before (pre) and after (post) surgery together with surgical tumor tissue were collected from each patient. Extracted RNA was enriched to construct library. Raw sequencing reads were aligned to hg19 human genome and miRNAs were annotated using miRBase v21. After reads normalization, differentially expressed miRNAs were identified through edgeR package. p-value < 0.01 was considered as statistically significant. miRNA deep sequencing analysis on 16 NSCLC patients: surgical tissue, pre-surgical and post-surgical serum samples lead to detect a total of 2500 miRNAs. MiRNA expression profile data were explained by the Venn diagram (figure1). MiR-125b-5p resulted significantly down-regulated in serum samples (pre and post-operative) compared to tumor tissue, while it increased in serum of patients after tumor removal. Therefore miR-125b-5p expression could be influenced by tumor resection because of its involvement in different tumorigenic processes. miRNA deep sequencing revealed circulating biomarkers potentially involved in lung tumor progression after surgery. MiRNAs could be useful to follow disease recurrence and to improve survival rate of early-stage patients.