RESEARCH ARTICLE COX-2 overexpression and -8473 T/C polymorphism in 3′ UTR in non-small cell lung cancer 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 Received: 15 April 2014 /Accepted: 29 July 2014 /Published online: 12 August 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014 Abstract A new class of compounds targeting cyclooxygen- ase 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 can- cer. 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 analy- sis, 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 geno- types 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 thresh- old ( 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 indi- cate 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. Keywords Polymorphism . Restriction fragment length polymorphism (RFLP) . Non-small cell lung cancer . RT-PCR . Western blotting Introduction Cyclooxygenase 2 (COX-2) is the key enzyme of prostaglan- din synthesis in inflamed tissues [1], and it also supports the mediation of prostaglandin implication in inflammation and angiogenesis and supports the growth of several solid tumors [2–4]. COX-2 expression has been reported in many human I. A. Bhat : R. Rasool : I. Qasim : Z. A. Shah (*) Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India e-mail: zaffaramin@gmail.com I. A. Bhat e-mail: imty82@gmail.com K. Z. Masoodi Department of Urology Research Laboratories, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA S. A. Paul Department of General Medicnine, Sheri Kashmir Institute of Medical Scinces, Medical College, Bemina , Srinagar, India B. A. Bhat Department of Plastic Surgery, Sher I Kashmir Institute Of Medical Sciences, Srinagar 190011, India F. A. Ganaie Department of Cardiovascular and Thoracic Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar 190011, India S. A. Aziz Department of Medical Oncology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar 190011, India Tumor Biol. (2014) 35:11209–11218 DOI 10.1007/s13277-014-2420-0