title: Cyclooxygenase-2 genetic variants influence intratumoral infiltration of Foxp3-positive regulatory T cells in non-small cell lung cancer.
abstract: The immune microenvironment of primary tumors has been reported to be a prognostic factor. We previously reported that the tumor-infiltrating regulatory T cell (Treg) count was positively correlated with the intratumoral cyclooxygenase-2 (COX-2) expression level and was associated with a poor survival among patients with non-small cell lung cancer (NSCLC). Recently, numerous single nucleotide polymorphisms (SNPs) in the COX-2 gene have been identified, and these SNPs may contribute to differential gene expression and enzyme activity levels. However, whether COX-2 genetic variants influence the functions of COX-2 in NSCLC remains unclear. Eighty NSCLC patients who underwent a complete resection at our institute were enrolled. We extracted DNA from the peripheral blood and identified five different COX-2 SNPs. The correlations between the COX-2 SNPs and the expression levels of COX-2, Tregs and Ki-67 were studied. The prognostic significance of the COX-2 SNPs was also evaluated. COX-2 SNPs were not correlated with the expression of COX-2. However, for the COX-2 -1195G/A polymorphism, the AA genotype group had a significantly higher Treg score. Furthermore, the AA group had a significantly higher Treg score regardless of the COX-2 expression level. The COX-2 -1195AA genotype group tended to have a shorter disease-free survival period than the GA/GG group. In conclusion, the COX-2 -1195G/A polymorphism influences the infiltration of Tregs into NSCLC, and the COX-2 SNP factor may be a prognostic factor reflecting Treg infiltration in NSCLC.
authors.affiliation: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Yukawa
authors.affiliation: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Saisho
authors.affiliation: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Riki
authors.initials: R
authors.lastname: Okita
authors.affiliation: Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Nakata
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000276:immunology / Q000401:mortality; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000276:immunology / Q000401:mortality; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018572:Disease-Free Survival; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human