title: miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.
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.
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Jian-fang
authors.initials: JF
authors.lastname: Lou
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Xin-hui
authors.initials: XH
authors.lastname: Shi
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Er-fu
authors.initials: EF
authors.lastname: Xie
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Rui-hong
authors.initials: RH
authors.lastname: Sun
authors.affiliation: Department of Pathology and Anatomic Pathology, Ronald Reagan Medical Center of UCLA, Santa Monica, CA, USA.
authors.forename: Jian-yu
authors.initials: JY
authors.lastname: Rao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Pu-wen
authors.initials: PW
authors.lastname: Huang
authors.affiliation: 1] Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China [2] National Key Clinical Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Shi-yang
authors.initials: SY
authors.lastname: Pan
authors.affiliation: Department of Respiratory, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C572154:MIRN638 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin