The single nucleotide polymorphism g.1548A >G (K469E) of the ICAM-1 gene is associated with worse prognosis in non-small cell lung cancer
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Intercellular adhesion molecule-1 (ICAM-1), a cell adhesion molecule with a key role in inflammation and immunosurveillance, has been implicated in carcinogenesis by facilitating instability of the tumor environment. The K469E single nucleotide polymorphism (SNP) (G>A) affects the ICAM-1 mRNA splicing pattern; the alternatively spliced isoform (ICAM-1-S) lacks transmembrane and intracellular domain, which affects the structural and signal transduction properties. Moreover, the expression of ICAM-1 is transcriptionally regulated by p53, and this SNP has been shown to be related with apoptosis. PCR-RFLP analysis was used to assess the K469E SNP status comparatively in 203 non-small cell lung cancer patients and 175 healthy sex-matched controls. This SNP was examined in relation to tumor kinetic parameters (Ki-67 immunohistochemical evaluation and Tdt-mediated dUTP nick end labeling assay), p53 immunohistochemistry status, and clinicopathological data in patients with operable stages. Both the genotype and allele frequency did not differ significantly between patients and controls. However, patients with the AG/AA genotypes had worse survival (39 vs 45 months, p = 0.036) and tended to be present in advanced stages (p = 0.057). Moreover, the AG/AA genotypes exerted a synergistic effect with aberrant p53 on tumor progression, while the GG genotype retained a better apoptotic index. The AG/AA genotypes correlated with worse survival and advanced stages probably due to defective immunosurveillance and apoptosis. These genetic backgrounds may confer a selective advantage for dissemination of tumor cells with high metastatic potential compared to GG genotype.
KeywordsICAM-1 Non-small cell lung cancer K469E polymorphism g.1548A >G p53
This work was financially supported by the European Commission FP7 projects INFLA-CARE (contract no. 223151), INsPiRE (contract no. 284460; REGPOT), the NKUA SARG grant no. 70/3/8916 and the “Hellenic Society of Medical Oncologists” grant (E. Thanopoulou). Both funding sources had no involvement, neither in the conduct of research nor in the preparation of the article.
Conflicts of interest
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