title: Survivin mRNA expression in blood as a predictor of the response to EGFR-tyrosine kinase inhibitors and prognosis in patients with non-small cell lung cancer.
abstract: The epidermal growth factor receptor (EGFR) mutations have been proven to be a reliable predictive marker for the response to EGFR-tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, the responses to EGFR-TKIs vary even among patients with EGFR mutation. Recent study showed that survivin overexpression attenuated EGFR-TKI-induced apoptosis and inhibited the antitumor effect of EGFR-TKIs on EGFR mutation NSCLC cells. We investigated the role of survivin mRNA expression in peripheral blood on predicting response and prognosis in NSCLC patients treated with EGFR-TKIs. Survivin mRNA expression levels in blood was detected using quantitative real-time-PCR assay in 62 patients with advanced NSCLC before (D0) and 4 weeks after treatment of EGFR-TKIs (D4w). The associations between survivin mRNA expression in blood and tumor response to treatment, time to progression (TTP), and overall survival (OS) were analyzed. Blood survivin mRNA levels at D0 and D4w were significantly higher in patients with progressive disease than in those with partial response and stable disease. The detections of blood survivin mRNA positivity at D0 and D4w were associated with unfavorable response to EGFR-TKIs treatment and shorter TTP and OS. Multivariate Cox analysis showed that blood survivin mRNA positivity before and 4 weeks after EGFR-TKIs treatment were independent predictor for worse TTP and OS. In conclusion, Blood survivin mRNA positivity was strongly related to a poor treatment outcome of EGFR-TKIs and may be a potential non-invasive biomarker for NSCLC treatment.
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: Quan-Lei
authors.initials: QL
authors.lastname: Bao
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Wu
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ge
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000401:mortality; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000097:blood*; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D000077022:Survivin; D016896:Treatment Outcome
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases