title: Dynamic changes in circulating miRNA levels in response to antitumor therapy of lung cancer.
abstract: OBJECTIVE
  Expression levels of cancer-associated microRNAs were reported to be altered in serum/plasma samples from lung cancer patients compared with healthy subjects. The purpose of this study was to estimate the value of five selected miRNAs plasma levels as markers of response to antitumor therapy in lung cancer patients.
  
  
  METHODS
  Expression levels of miR-19b, miR-126, miR-25, miR-205, and miR-125b have been evaluated by quantitative reverse transcription PCR versus control miR-16 in blood plasma samples from 23 lung cancer (LC) patients. Plasma samples were obtained from LC patients before treatment (untreated-UT), within 30 days after completing two courses of chemotherapy (postchemotherapy-PC) and 15 days after surgery (postoperative-PO).
  
  
  RESULTS
  Repeated Measures ANOVA demonstrated that miR-19b expression levels were decreased in PC and increased in PO samples. These changes were characterized by a significant quadratic trend (p = 0.03). Expression levels of miR-125b increased both after chemotherapy and again after surgery and demonstrated a significant linear trend (p = 0.03). The miR-125b/miR-19b ratio changed during the course of the antitumor treatment with a significant linear trend (p = 0.04). Individual analysis in the groups of patients with partial response to chemotherapy and patients with stable or progressive disease showed different trends for miR-19b, miR-125b, and miR-125b/miR-19b ratio between the groups. The Kaplan-Meier survival curves demonstrated an association of miR-125b/miR-19b ratio value with the survival time without the tumor relapse (p < 0.1).
  
  
  CONCLUSIONS
  Dynamic change of trends for miR-19b and miR-125b expression levels and miR-125b/miR-19b ratio in the blood plasma have shown a potentiality to discriminate types of response to antitumor therapy in lung cancer patients. Further in-depth investigation is needed to establish a direct link the miRNAs expression levels in blood plasma with therapy response and patient's survival.
authors.affiliation: a Tomsk Cancer Research Institute , Tomsk, Russia.|c National Research Tomsk Polytechnic University , Tomsk, Russia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Ponomaryova
authors.affiliation: b Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk, Russia.|d Novosibirsk Research Institute of Circulation Pathology Academician E.N. Meshalkin , Novosibirsk, Russia.
authors.forename: Evgeny S
authors.initials: ES
authors.lastname: Morozkin
authors.affiliation: b Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk, Russia.|f Novosibirsk State Technical University, Novosibirsk, Russia.
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Rykova
authors.affiliation: b Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk, Russia.|d Novosibirsk Research Institute of Circulation Pathology Academician E.N. Meshalkin , Novosibirsk, Russia.
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Zaporozhchenko
authors.affiliation: b Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk, Russia.
authors.forename: Tatyana E
authors.initials: TE
authors.lastname: Skvortsova
authors.affiliation: a Tomsk Cancer Research Institute , Tomsk, Russia.
authors.forename: Аlexey Y
authors.initials: АY
authors.lastname: Dobrodeev
authors.affiliation: a Tomsk Cancer Research Institute , Tomsk, Russia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Zavyalov
authors.affiliation: a Tomsk Cancer Research Institute , Tomsk, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Tuzikov
authors.affiliation: b Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk, Russia.
authors.forename: Valentin V
authors.initials: VV
authors.lastname: Vlassov
authors.affiliation: a Tomsk Cancer Research Institute , Tomsk, Russia.|e National Research Tomsk State University , Tomsk , Russia.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Cherdyntseva
authors.affiliation: b Institute of Chemical Biology and Fundamental Medicine SB RAS , Novosibirsk, Russia.|d Novosibirsk Research Institute of Circulation Pathology Academician E.N. Meshalkin , Novosibirsk, Russia.
authors.forename: Pavel P
authors.initials: PP
authors.lastname: Laktionov
authors.affiliation: a Tomsk Cancer Research Institute , Tomsk, Russia.
authors.forename: Evgeny L
authors.initials: EL
authors.lastname: Choinzonov
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: blood plasma; cell-free miRNA; combined antitumor therapy; lung cancer; non-invasive diagnostics; therapy response