1.miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.
Fang WANG ; 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
Experimental & Molecular Medicine 2015;47(5):e162-
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.
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
2.miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.
Fang WANG ; 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
Experimental & Molecular Medicine 2015;47(5):e162-
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.
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