A polymorphic -844T/C in FasL promoter predicts survival and relapse in non-small cell lung cancer

Wen Wei Sung, Yao Chen Wang, Ya Wen Cheng, Ming Ching Lee, Kun Tu Yeh, Lee Wang, John Wang, Chih Yi Chen, Huei Lee

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Abstract

Purpose: Fas ligand (FasL) -844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL -844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL -844T/C polymorphism on the clinical outcome of non-small cell lung cancer (NSCLC) remains to be identified. Experimental Design: A total of 385 adjacent normal lung tissues from patients with NSCLC were collected to determine FasL -844T/C polymorphism by PCR-based restriction fragment length polymorphism. FasL mRNA and protein expression in lung tumors were evaluated by real-time PCR and immunohistochemistry. The prognostic value of FasL -844T/C polymorphism on survival and relapse was determined by Kaplan-Meier analysis and Cox proportional hazards models. Results: The FasL -844CC genotype had higher prevalence in those with advanced tumors than in those with early tumors (P = 0.008). In addition, patients with the FasL -844CC genotype were more prone to tumor relapse than those with the FasL -844TT+TC genotype (62.1% vs. 37.9%, P = 0.001). Multivariate Cox regression analysis showed that patients with the FasL -844CC genotype had poorer survival in terms of overall survival (OS) and relapse-free survival (RFS) than those with the FasL -844TT+TC genotype (24.1 vs. 42.8 months for OS, HR = 1.455, P = 0.004; 15.4 vs. 31.4 months for RFS, HR = 1.710, P <0.001). Conclusions: FasL -844T/C polymorphism may predict survival and relapse in NSCLC. We suggest that FasL may be a molecular target for immunotherapeutic interventions to improve the clinical outcome of patients with NSCLC. This finding should be validated by another investigative group.

Original languageEnglish
Pages (from-to)5991-5999
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number18
DOIs
Publication statusPublished - Sep 15 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sung, W. W., Wang, Y. C., Cheng, Y. W., Lee, M. C., Yeh, K. T., Wang, L., Wang, J., Chen, C. Y., & Lee, H. (2011). A polymorphic -844T/C in FasL promoter predicts survival and relapse in non-small cell lung cancer. Clinical Cancer Research, 17(18), 5991-5999. https://doi.org/10.1158/1078-0432.CCR-11-0227