Predictive value of STMN1 gene promoter polymorphism (-2166T>C) in patients with advanced NSCLC treated with the combination of platinum compounds and vinorelbine

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Abstract

Purpose: 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. Conclusion: Rare TT genotype of STMN1 gene may be an unfavorable predictive factor of chemotherapy based on platinum compounds and vinorelbine, in patients with NSCLC.

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Mlak, R., Krawczyk, P., Ciesielka, M., Homa, I., Powrózek, T., Prendecka, M., … Małecka-Massalska, T. (2015). Predictive value of STMN1 gene promoter polymorphism (-2166T>C) in patients with advanced NSCLC treated with the combination of platinum compounds and vinorelbine. Cancer Chemotherapy and Pharmacology, 76(3), 621–629. https://doi.org/10.1007/s00280-015-2831-7

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