Despite decades of efforts,
non-small-cell lung cancer (NSCLC) remains the leading cause of
cancer mortality globally primarily due to the challenge in early detection of the
cancer. Being an important player in
cancer development, the dysregulated
miRNAs have been shown promising values as non-invasive diagnostic and prognostic
biomarkers for NSCLC. The aim of our study is to access the efficacy and reliability of a potential circulating
miRNA panel in early diagnosis of NSCLC. We first selected eight candidate
miRNAs, miR-146b, miR-205, miR-29c, miR-31, miR-30b, miR-337, miR-411, and miR-708, which have been shown frequently aberrant in primary NSCLC patients based on our previous studies and other reports. The serum level of each of these
miRNAs was evaluated by quantitative real-time PCR (qRT-PCR) in training and testing sets. We found that 5 out of 8
miRNAs (miR-146b, miR-205, miR-29c, miR-30b, and miR-337) were significantly up-regulated in NSCLCs patients compared to healthy or
cancer-free controls in both training and testing sets. Based on the logistic regression model, a 4-miRNAs set (miR-146b, miR-205, miR-29c and miR-30b) was picked out of the 5
miRNAs owing to its excellent diagnostic power for NSCLC patients in the training set (AUC=0.99, accuracy=95.00%), the testing set (AUC=0.93, accuracy=89.69%), and the training-testing combined set ( AUC=0.96, accuracy=92.00%). When pathological subtypes of NSCLC are compared, this 4-miRNA panel carried a relatively higher prediction power and higher sensitivity for
adenocarcinoma (AC) (AUC=0.98, sensitivity=99.10%) than for
squamous cell carcinoma (SCC) (AUC=0.93, sensitivity=90.32%). Additionally, this panel demonstrated a comparable diagnostic capacity for stage I (AUC=0.96) and stage II-III (AUC=0.95) of NSCLC, suggesting its role in reflecting the
tumor load. Importantly, the high levels of miR-146b and miR-29c in serum were significantly associated with poor 5-year overall survival (OS) (both p=0.04). Further survival analysis showed that high level of miR-146b in serum is specifically correlated with poor survival rate in SCC patients (p=0.0035) but not in AC patients (p=0.83), consistent with our previous finding that the high tissue expression of miR-146b in
lung cancer specimen is indicative of a poor prognosis for SCC patients. Altogether, our study demonstrated that the 4-miRNA panel is a novel, sensitive and non-invasive
serum marker for the early diagnosis of NSCLC.