Exp Mol Med.
2015 May;47(5):e162. 10.1038/emm.2015.17.
miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy
- Affiliations
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- 1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. sypan@njmu.edu.cn
- 2National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
- 3Department of Pathology and Anatomic Pathology, Ronald Reagan Medical Center of UCLA, Santa Monica, CA, USA.
- 4Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
- 5Department of Respiratory, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. hongwang@njmu.edu.cn
- KMID: 2155654
- DOI: http://doi.org/10.1038/emm.2015.17
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.
MeSH Terms
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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
Antineoplastic Agents
Biomarkers, Tumor
Cisplatin
MicroRNAs
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