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01-11-2014 | Research Article

COX-2 overexpression and -8473 T/C polymorphism in 3′ UTR in non-small cell lung cancer

Authors: Imtiyaz A. Bhat, Roohi Rasool, Iqbal Qasim, Khalid Z. Masoodi, Shabeer A. Paul, Bashir A. Bhat, Farooq A. Ganaie, Sheikh A. Aziz, Zafar A. Shah

Published in: Tumor Biology | Issue 11/2014

Abstract

A new class of compounds targeting cyclooxygenase 2 (COX-2) together with other different clinically used therapeutic strategies has recently shown a promise for the chemoprevention of several solid tumors including lung cancer. The aim was to study the possible role of COX-2 -8473 T/C NP and its expression in the pathogenesis of non-small cell lung cancer. One hundred ninety non-small cell lung cancer (NSCLC) patients and 200 healthy age-, sex-, and smoking-matched controls were used for polymorphic analysis, and 48 histopathologically confirmed NSCLC patients were analyzed for COX-2 messenger RNA (mRNA) and protein expression. Our results showed that the frequencies of variant genotypes 8473 CT/CC were significantly less common in the cases (30.0 %) than in the controls (36 %), suggesting that the 8473C variant allele is related with lower susceptibility in NSCLC (OR = 0.79, 95 % CI 0.54–1.4). However, the frequency of COX-2 -8473 TC and CC genotypes were significantly associated with age in NSCLC (P = 0.02). Quantitative real-time expression analysis showed a significant increase in the COX-2 mRNA in tumor tissues as compared to their adjacent normal tissues [delta cycle threshold (ΔCT) = 9.25 ± 4.67 vs 5.63 ± 3.85, P = 0.0001]. Multivariate logistic regression analyses revealed that the COX-2 expression was associated significantly with age (P = 0.044). Also, an increasing trend was observed in stages I and II and in female patients compared to stages III and IV and male patients, respectively, but no statistical significance was observed. However, COX-2 mRNA expression shown no association with the -8473C variant allele. Our findings indicate that the COX-2 T8473C polymorphism may contribute to NSCLC cancer susceptibility in the Kashmiri population, while our expression analysis revealed a significant increase of COX-2 in tumor tissues as compared to their adjacent normal tissues, suggesting that it could become an important therapeutic marker in NSCLC in the future.

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Title: COX-2 overexpression and -8473 T/C polymorphism in 3′ UTR in non-small cell lung cancer
Authors: Imtiyaz A. Bhat
Roohi Rasool
Iqbal Qasim
Khalid Z. Masoodi
Shabeer A. Paul
Bashir A. Bhat
Farooq A. Ganaie
Sheikh A. Aziz
Zafar A. Shah
Publication date: 01-11-2014
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 11/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-014-2420-0

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