Circulating miR-125b is a novel biomarker for screening non-small-cell lung cancer and predicts poor prognosis

Abstract

Purpose: MicroRNAs are small, non-coding RNAs that are critical regulators of various diseases including cancer, and may represent a novel class of cancer biomarkers. Recent reports have highlighted the oncogenic aspects of miR-125b. However, the level and clinical relevance of circulating miR-125b transcripts in human serum of non-small-cell lung cancer (NSCLC) patients are unclear. The purpose of this study was to identify circulating miR-125b transcripts in human serum for use as a biomarker for stratification and prediction of prognosis in NSCLC.

Methods: We analyzed serum levels of miR-125b in 193 patients with different stages of NSCLC. Blood samples were collected before surgery and therapy. Quantitative reverse transcription-polymerase chain reaction of circulating miR-125b transcripts was performed directly in serum to improve the efficiency of miRNA assessment. Receiver operating characteristic analysis was used to evaluate the sensitivity and specificity of serum miR-125b.

Results: We found that serum miR-125b was consistently expressed in the non-tumor group and was significantly associated with NSCLC stage. miR-125b expression was capable of separating NSCLC patients from control groups with an area under the curve of 0.786. Furthermore, patients with high miR-125b expression displayed a significantly poorer prognosis compared with patients with low expression (p < 0.0001). Multivariate analysis indicated that high miR-125b expression was an independent prognostic factor for survival.

Conclusions: We propose that serum miR-125b may represent a novel biomarker in NSCLC patients and that high miR-125b expression is an independent prognostic factor for survival.

Fig. 1

Serum miR-125b levels in healthy controls and non-small-cell lung cancer (NSCLC) patients. a The Mann–Whitney test was performed to examine the difference in serum miR-125b levels between normal controls and NSCLC patients. b Further comparison between controls and stages I–IV NSCLC patients

Fig. 2

Receiver operating characteristic (ROC) analysis was performed to determine the sensitivity and specificity of miR-125b expression level using area under the ROC curve (AUC). a Separating NSCLC patients from control group, b separating stages I–II from control group; AUC, sensitivity and specificity are 0.660, 96.1 and 38.2 %, respectively. c Separating stage III from control group, AUC, sensitivity and specificity are 0.836, 92.6 and 66.4 %, respectively. d Separating stage IV from control group, AUC, sensitivity and specificity are 0.895, 95.2 and 67.3 %, respectively. e Separating stages I–II from stage III, AUC, sensitivity and specificity are 0.776, 81.5 and 68.4 %, respectively. f Separating stage III from stage IV, AUC, sensitivity and specificity are 0.665, 41.3 and 96.3 %, respectively

Fig. 3

Kaplan–Meier estimates of postoperative survival times of NSCLC patients according to serum miR-125b expression. The expression levels of serum miR-125b in 193 patients were measured by quantitative reverse transcription–polymerase chain reaction directly in serum samples (qRT–PCR–DS). NSCLC patients with values less than the median expression of miR-125b in NSCLC patients were assigned to the low-expression group (n = 96), whereas those with expression values above the median were assigned to the high-expression group (n = 97). Log-rank p values are from Kaplan–Meier analysis