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

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

SUBMITTER: Mlak R

PROVIDER: S-EPMC4540763 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Mlak Radosław R Krawczyk Paweł P Ciesielka Marzanna M Homa Iwona I Powrózek Tomasz T Prendecka Monika M Kozioł Piotr P Milanowski Janusz J Małecka-Massalska Teresa T

Cancer chemotherapy and pharmacology 20150729 3

<h4>Purpose</h4>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 format ...[more]

PMID: 26220844

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Project description:BackgroundCD73 induces the dephosphorylation of adenosine monophosphate converting it to adenosine, enabling malignancies to escape from immune surveillance. Although CD73 overexpression has been reported to be a poor prognostic factor in several malignancies including non-small cell lung cancer (NSCLC), its predictive relevance in NSCLC patients receiving immune checkpoint inhibitors is unknown. The present research was conducted to investigate the prognostic significance of CD73 expression in NSCLC patients receiving immune checkpoint inhibitors (ICIs).MethodsWe screened 91 patients with advanced or recurrent NSCLC who received immune checkpoint inhibitors. CD73 expression was evaluated immunohistochemically using tissue specimens obtained just before treatment with ICIs.ResultsAnalysis of progression-free survival (PFS) and overall survival (OS) in relation to several levels of CD73 expression (1%, 10%, 30%, and 50%) showed that both tended to be more favorable as expression of CD73 increased. PFS and OS were longer for patients in whom at least 50% of the tumor cells expressed CD73 than for those in whom <50% of the tumor cells did so. In patients who were positive for EGFR mutation, immune checkpoint inhibitors were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation-negative NSCLC. Furthermore, CD73 expression was predictive factor for the PFS independent of PD-L1 expression in patients with EGFR mutation.ConclusionsHigh CD73 expression may predict a favorable response to ICIs in NSCLC patients, especially those harboring EGFR mutations.Key pointsSignificant findings of the study: In patients who were positive for EGFR mutation, immune checkpoint inhibitors (ICIs) were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation-negative NSCLC.What this study addsHigh CD73 expression may predict a favorable response to immune checkpoint inhibitors in NSCLC patients, especially those harboring EGFR mutations.

Dataset Information

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

Publications

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

Similar Datasets

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