Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer

Abstract

Studies have shown cell鄄 free microRNA (miRNA) circulating in the serum and plasma with specific expression in cancer, indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy. This study was to investigate whether plasma miRNA鄄 21 (miR鄄 21) can be used as a biomarker for the early detection of non-small cell lung cancer (NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum鄄 based chemotherapy. We used real鄄 time RT鄄 PCR to investigate the expression of miR鄄 21 in the plasma of 63 NSCLC patients and 30 healthy controls and correlated the findings with early diagnosis, pathologic parameters, and treatment. Thirty鄄 five patients (stages IIIB and IV) were evaluable for chemotherapeutic responses: 11 had partial response (PR); 24 had stable and progressive disease (SD+ PD). Plasma miR鄄 21 was significantly higher in NSCLC patients than in age鄄 and sex鄄 matched controls (P < 0.001). miR鄄 21 was related to TNM stage (P < 0.001), but not related to age, sex, smoking status, histological classification, lymph node status, and metastasis (all P > 0.05). This marker yielded a receiver operating characteristic (ROC) curve area of 0.775 (95% CI: 0.681 -0.868) with 76.2% sensitivity and 70.0% specificity. Importantly, miR鄄 21 plasma levels in PR samples were several folds lower than that in SD plus PD samples (P = 0.049), and were close to that in healthy controls (P = 0.130). Plasma miR鄄 21 can serve as a circulating tumor biomarker for the early diagnosis of NSCLC and is related to the sensitivity to platinum鄄 base chemotherapy.

Lung Cancer Detection by Screening - Presenting Circulating miRNAs as a Promising Next Generation Biomarker Breakthrough

“…miR21 was shown to be several folds lower in patients with a partial response and to be a biomarker for early diagnosis of NSCLC. Plasma miR-21 could predict sensitivity to platinum based chemotherapy as well (Wei et al, 2011).…”

MicroRNAs in Body Fluids as Biomarkers for Non-Small Cell Lung Cancer: A Systematic Review

“…Jeong et al found the expression of let-7a miRNA is lower in NSCLC tissues than in normal lung tissues (24). Blood miR-21 was found up-regulated in pancreatic cancer (38,39) as well as NSCLC (29,40), so several miRNAs are dysregulated as a phenomenon of cancer rather than due to a specific cancer. Different expression of miRNAs has been reported in human NSCLC, fewer studies to date have examined whether circulating miRNA levels could be useful in differentiating NSCLC from control groups.…”

“…MiR-16 was proven as one of commonly used internal control genes to determine expressions of miRNAs as shown in previous work (25,26,46). In our included studies, three papers used miR-16 as internal control genes to normalize miRNA level (25,26,40).…”

“…The reliability of these miRNAs is still debatable. Moreover, the same miRNAs could be biomarkers in diverse diseases (29,(40)(41)(42). This study therefore aimed at the identification and evaluation of miRNAs in body fluids to predict NSCLC.…”

The role of genetic and other biomarkers in NSCLC prognosis

“…Plasma miR-21 expression may correlate with sensitivity to chemotherapy too. NSCLC patients who underwent 2 to 3 cycles of platinum-based therapy and reached partial response or stable disease effect had higher miR-21 expression compared with patients who had progression of the disease after treatment (p=0.049) [47].…”