During the last few years a growing number of studies has attempted to shed light on the role of CD40 (Tumor Necrosis Factor Receptor Superfamily Member 5) in non-small-cell lung cancer (NSCLC), which remains the leading cause of cancer-related deaths worldwide. The aim of the current study was to investigate the clinical relevance of CD40 functional single nucleotide polymorphism (SNP) rs1883832 (-1C/T) with susceptibility to NSCLC, the clinicopathological parameters, relapse and survival rates of NSCLC patients, as well as with the protein expression of CD40.
CD40 SNP rs1883832 was genotyped in 268 randomly selected NSCLC patients and 279 age- and gender-matched healthy donors. Patients were under observation during a five-year period. Immunohistochemical analysis for CD40 was performed on 106 NSCLC tumor tissue samples. All the participants were Greeks with Caucasian origin.
Genotype frequencies of rs1883832 (CC, CT, and TT) were significantly different between healthy controls and patients. CC homozygotes had higher risk for NSCLC compared to T allele carriers in univariate (P < 0.001), as well as in multivariate analysis (P = 0.006). In addition, rs1883832 was related to overall survival. More specifically, CT heterozygotes had worse clinical outcome after two-, three- and five-year observation compared to TT and CC homozygotes (P = 0.015, P = 0.005 and P = 0.017, respectively). Stratifying according to histological subtype, this association was observed only in patients with adenocarcinomas (P = 0.028) and not in patients with squamous- and large-cell carcinomas. Furthermore, taking into consideration disease stage, worse survival for CT heterozygotes was observed in stage II patients and not in patients of other stages (P = 0.016). Moreover, the variant had also strong association with brain metastases, with T allele carriers developing more often metastatic disease in CNS (P = 0.018). Interestingly, rs1883832 was related to CD40 protein expression in malignant cells (P < 0.001) as well as in stromal cells (P = 0.004).
The present findings suggest that investigated SNP rs1883832 may be a useful and independent biomarker in NSCLC. However, more studies are needed in order to further demonstrate their role in NSCLC.
Clinical trial identification
Legal entity responsible for the study
University of Patras.
Has not received any funding.
All authors have declared no conflicts of interest.