A Polymorphic −844T/C in FasL Promoter Predicts Survival and Relapse in Non–Small Cell Lung Cancer

Abstract

Purpose: Fas ligand (FasL) À844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL À844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL À844T/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 À844T/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 À844T/C polymorphism on survival and relapse was determined by Kaplan-Meier analysis and Cox proportional hazards models.Results: The FasL À844CC genotype had higher prevalence in those with advanced tumors than in those with early tumors (P ¼ 0.008). In addition, patients with the FasL À844CC genotype were more prone to tumor relapse than those with the FasL À844TTþTC genotype (62.1% vs. 37.9%, P ¼ 0.001). Multivariate Cox regression analysis showed that patients with the FasL À844CC genotype had poorer survival in terms of overall survival (OS) and relapse-free survival (RFS) than those with the FasL À844TTþTC genotype (24

IL-10 Promotes Tumor Aggressiveness via Upregulation of CIP2A Transcription in Lung Adenocarcinoma

“…Genomic DNA was extracted from tissues and cell lines by conventional methods, as described previously (19).…”

“…RNA extraction and cDNA synthesis from tumor tissues and cells RNA extraction and cDNA synthesis were conducted as described previously (19).…”

“…The detail method was described previously (19). Realtime RT-PCR primers are listed in Supplementary Table S1.…”

New Strategies in Lung Cancer: Translating Immunotherapy into Clinical Practice

“…After resection of NSCLC, high-level CD4 þ /CD8 þ T-cell infiltration in the tumor is associated with improved survival, whereas higher levels of regulatory T-cell infiltration predicts a higher risk of relapse (21,22). More recently, Fas ligand polymorphisms have been shown to affect immune-mediated resistance to NSCLC growth and metastasis, whereas variations in cytokine haplotypes may also affect the innate immune response to nascent NSCLC (17,23). Clinical development of immunotherapy for NSCLC has involved two broad classes of agents, allogeneic vaccines and immune checkpoint inhibitors.…”

The Relationship of Fas Promoter Polymorphisms and Breast Cancer Risk in North-West of Iran: A Haplotype and in Silico Analysis

“…Death receptor on the surface of many cell types, fas and its ligand, fasL as members of the tumor necrosis factor superfamily (TNF), interact to initiate the extrinsic death signal pathway, which consequently leads to apoptotic cell death (7,(9)(10)(11)(12). Structural alterations of fas and fasL may influence the expression of them and consequently result in the development of various tumors, such as breast tumors (7,13). The human fas on 10q24.1 (12,14), which consists of 9 exons and 8 introns, (14) has 2 single nucleotide polymorphisms (SNPs) in its promoter.…”