title: CK-19 mRNA-positive cells in peripheral blood predict treatment efficacy and survival in small-cell lung cancer patients.
abstract: Small-cell lung caner (SCLC) is the most aggressive form of lung cancer. The aim of this study was to investigate whether the presence of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) predicts treatment response, progression-free survival (PFS), and overall survival (OS) in SCLC patients who received standard therapy. Fifty-five SCLC patients were enrolled in this single-center prospective study. CK-19 mRNA-positive CTCs in blood samples were detected using real-time quantitative-PCR assay before the initiation of chemotherapy (B0) and after one chemotherapy cycle (B1) and three chemotherapy cycles (B3). The association with known prognostic factors and the effect of CK-19 mRNA-positive CTCs on patients' prognosis were analyzed. Patients with positivity for CK-19 mRNA-positive CTCs at B0, B1, and B3 time points had shorter PFS and OS compared with patients without (P = 0.014 and P = 0.01, respectively, at B0; P = 0.008 and P = 0.002, respectively, at B1; P = 0.003 and P = 0.001, respectively, at B3). Conversion of initial positivity for CK-19 mRNA-positive CTCs to negativity at B1 and B3 time points was associated with longer PFS and OS compared with patients with persistent positivity at three time points (P = 0.008 and P = 0.010, respectively). Multivariate analysis demonstrated that the presence of CK-19 mRNA-positive CTCs at B0, B1, and B3 time points remained strong predictors of PFS and OS after adjustment for clinically significant factors. In conclusion, detection of CK-19 mRNA-positive CTCs before and during chemotherapy is an accurate indication of subsequent disease progression and mortality for SCLC patients.
authors.affiliation: Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, 438 North Jiefang Street, Zhenjiang, 212001, China.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Shi
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Du
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Hu
authors.forename: Yong-Chang
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D053539:Keratin-19 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D053539:Keratin-19; D012333:RNA, Messenger