miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.
- Author:
Fang WANG
1
;
Jian Fang LOU
;
Yan CAO
;
Xin Hui SHI
;
Peng WANG
;
Jian XU
;
Er Fu XIE
;
Ting XU
;
Rui Hong SUN
;
Jian Yu RAO
;
Pu Wen HUANG
;
Shi Yang PAN
;
Hong WANG
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH: Animals; Antineoplastic Agents/*therapeutic use; Biomarkers, Tumor/blood/genetics; Carcinoma, Non-Small-Cell Lung/blood/diagnosis/*drug therapy/genetics; Cell Line, Tumor; Cisplatin/*therapeutic use; Female; Gene Expression Regulation, Neoplastic/drug effects; Humans; Lung/*drug effects/metabolism/pathology; Lung Neoplasms/blood/diagnosis/*drug therapy/genetics; Male; Mice; Mice, Nude; MicroRNAs/blood/*genetics; Middle Aged; Prognosis; Survival Analysis; Treatment Outcome
- From:Experimental & Molecular Medicine 2015;47(5):e162-
- CountryRepublic of Korea
- Language:English
- Abstract: MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.