Serum miR-499 as a novel diagnostic and prognostic biomarker in non-small cell lung cancer

Abstract

Abstract. The aim of the present study was to determine whether serum miR-499 may be used as a biomarker for early detection of non-small cell lung cancer (NSCLC). The present study was designed as an initial screening phase and a subsequent validation phase. In the screening phase, we analyzed serum levels of miR-499 in a subset of 40 patients with stage I (n=20) and stage IV (n=20) NSCLC. In the validation phase, miR-499 expression levels in serum (n=514) and tissue (n=136) from NSCLC patients were detected in a large and independent cohort of 514 patients. miR-499 in the screening phase was found to be significantly elevated in the serum of stage I NSCLC patients compared with that in stage IV NSCLC patients (P<0.001). Validation analysis showed that serum miR-499 levels were robust in differentiating NSCLC patients from control subjects [area under the curve (AUC)=0.906; 95% confidence interval (CI)=0.879 to 0.929). Serum miR-499 levels were significantly lower in stage III and IV patients compared with those with stage I (both P<0.001) or II (both P<0.001). Low serum miR-499 levels were associated with shorter overall survival and served as an independent prognostic biomarker in NSCLC patients [hazard ratio (HR)=1.63; 95% CI=1.33-2.0; P<0.0001). In addition, low serum levels of miR-499 indicated a poor disease-free survival in stage I-II NSCLC patients. Serum miR-499 may prove to be a promising biomarker for early detection and prognosis prediction of NSCLC.

Circulating myomiRs: a new class of biomarkers to monitor skeletal muscle in physiology and medicine

“…However, alterations in circulating myomiRs are also reported in several non‐muscle cancers. Gastric cancer induced a 2‐fold increase in miR‐1, but in most malignant diseases studied, such as non‐small cell lung cancer, melanoma, astrocytoma, or osteosarcoma, circulating myomiRs were lower in patients than in the control population . Both miR‐206 and miR‐133 (a and b) have tumour suppressor properties, and they are down‐regulated within several tumours; a link between low expression and tumour development has been proposed (for review, refer to Nohata et al …”

“…Thus, a more convincing hypothesis links cancer progression, muscle mass, and myomiRs. In many cancers, low circulating myomiRs are reported to predict unfavourable prognosis and survival . Limited information on muscle damage biomarkers or muscle mass is given in those studies.…”

“…Gastric cancer induced a 2-fold increase in miR-1, 52 but in most malignant diseases studied, such as non-small cell lung cancer, melanoma, astrocytoma, or osteosarcoma, circulating myomiRs were lower in patients than in the control population. [53][54][55][56][57] Both miR-206 and miR-133 (a and b) have tumour suppressor properties, and they are down-regulated within several tumours; a link between low expression and tumour development has been proposed (for review, refer to Nohata et al 58 ). However, it is unclear how low expression in tumours could result in decreased circulating levels in patients with cancer compared with healthy subjects.…”

Distinct functions of dynamin isoforms in tumorigenesis and their potential as therapeutic targets in cancer

“…It has been reported to enhance the apoptotic effect of the death receptor ligand TRAIL in human ovarian cancer [57]. Low serum MiR-499 expression was associated with advanced tumor node metastasis (TNM) stage and poor prognosis [89]. Overexpression of MiR-499-5p inhibited cell proliferation and induced apoptosis in vitro as well as in vivo.…”

Whole blood FPR1 mRNA expression predicts both non‐small cell and small cell lung cancer

“…Other groups have explored the utility of blood and nonblood‐based biomarkers for lung cancer screening. A representative list include using gene expression of peripheral blood mononuclear cells, serum proteins, microRNAs, immunoassay, methylation, exhaled volatile organic compounds and urine protein biomarkers . Unlike other blood‐based lung cancer detection methods, the FPR1 ratio has been demonstrated to detect both NSCLC and SCLC.…”