Background:Cancer stem cells (CSCs) are believed to cause local recurrence, distant metastasis, radiotherapy and chemotherapy resistance.
Aim: We hypothesized that genetic variation in CD133 (the official name is PROM1), one of the most important marker genes of CSCs, may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy.
Methods:We identified 393 patients with primary NSCLC between March 1998 and Feb 2009, who were treated with definitive radiotherapy at our institution. We genotyped four potential functional single nucleotide polymorphisms (SNPs) of PROM1 (rs2240688A>C; rs10022537A>T; rs7686732G>C; and rs3130T>C.) and estimated their associations with local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) by Cox proportional hazards model.
Results:Only genotypes of rs2240688 were significant associated with LRFS, DMFS, and OS. Patients with the rs2240688AC genotype were associated with longer LRFS, DMFS, and OS than patients with the AA genotype (P = 0.022, 0.019, 0.039, respectively, by Cox model with adjustment for clinical characters). Patients with AC/CC genotypes of rs2240688 had longer LRFS, DMFS, and OS than patients with AA genotypes (P = 0.016, 0.018, 0.044, respectively, by Cox model with adjustment for clinical characters). In the stratification analysis, LRFS, DMFS, and OS associated with rs2240688 had contrary predictive trends in early disease stage [HR=2.79, 95%CI (1.08-7.22); HR=2.66, 95%CI (1.03-6.87); and HR=3.26, 95%CI (1.23-8.61), respectively] and advanced disease stage [HR=0.63, 95%CI (0.48-0.83); HR=0.67, 95%CI (0.51-0.88); and HR=0.64, 95%CI (0.48-0.85), respectively] by Cox model with adjustment for patients’ characteristics. Furthermore, the results remained significant multiplicative interactions in multivariate Cox models, P value were 0.025, 0.039, and 0.021, respectively.
Conclusions: Our data suggest that functional SNPs rs2240688 in cancer stem cell marker gene PROM1 could predict radiotherapy and chemotherapy resistance among NSCLC patients, might be a promising biomarker of CSCs to predict prognosis and optimize treatment strategies.