title: Predictive value of STMN1 gene promoter polymorphism (-2166T>C) in patients with advanced NSCLC treated with the combination of platinum compounds and vinorelbine.
abstract: OBJECTIVE
  The combination of platinum compounds and vinorelbine is often used as a first-line treatment in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), without activating EGFR mutations and ALK rearrangement. Unfortunately, less than half of the patients benefit from chemotherapy. Moreover, majority of patients are exposed to a number of side effects of chemotherapy. Stathmin-1 (STMN1, oncoprotein 18) affects significantly microtubule dynamics and formation of the mitotic spindle. Therefore, the change in the STMN1 gene may be a potential predictive factor of response to treatment regimens containing a cytostatics-disrupting microtubule dynamics (vinca alkaloids and taxoids). The aim of the study was to determine the relationship between a single nucleotide polymorphism (SNP) of the promoter of STMN1 gene -2166T>C) and the effectiveness of chemotherapy based on platinum compounds and vinorelbine in patients with NSCLC.
  
  
  METHODS
  The investigated population consisted of 110 locally advanced or metastatic NSCLC patients treated with first-line chemotherapy, based on platinum compounds and vinorelbine. SNP was determined by SNaPshot™ PCR in DNA isolated from peripheral blood leukocytes.
  
  
  RESULTS
  The median progression-free survival (PFS) was significantly shorter in carriers of TT genotype of the STMN1 gene compared with patients with CC or CT genotypes (2.75 vs. 6.5 months; p = 0.0033; HR 5.91, 95% CI 1.81-19.33). Evaluated SNP did not significantly affect the response to treatment and the overall survival of the patients.
  
  
  CONCLUSIONS
  Rare TT genotype of STMN1 gene may be an unfavorable predictive factor of chemotherapy based on platinum compounds and vinorelbine, in patients with NSCLC.
authors.affiliation: Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland, radoslaw.mlak@gmail.com.
authors.forename: Radosław
authors.initials: R
authors.lastname: Mlak
authors.forename: Paweł
authors.initials: P
authors.lastname: Krawczyk
authors.forename: Marzanna
authors.initials: M
authors.lastname: Ciesielka
authors.forename: Iwona
authors.initials: I
authors.lastname: Homa
authors.forename: Tomasz
authors.initials: T
authors.lastname: Powrózek
authors.forename: Monika
authors.initials: M
authors.lastname: Prendecka
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozioł
authors.forename: Janusz
authors.initials: J
authors.lastname: Milanowski
authors.forename: Teresa
authors.initials: T
authors.lastname: Małecka-Massalska
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D050777:Stathmin / Q000235:genetics* / Q000378:metabolism; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D004273:DNA, Neoplasm; D017671:Platinum Compounds; C493995:STMN1 protein, human; D050777:Stathmin; D014747:Vinblastine; D000077235:Vinorelbine