Intratumoral polymorphism of peroxisome proliferator-activated receptor delta -87 T>C in colorectal cancer

Bin Luo, Hong-Wei Yang, Fei-Wu Long, Bin Zhou, Zhao-Ying Lv, Ke-Ling Cheng, Yuan Li,  Zong-Guang Zhou,  Xiao-Feng Sun

Abstract:

Peroxisome proliferator-activated receptor delta (PPARD) is a nuclear receptor transcription factor whose single nucleotide polymorphism (SNP), especially PPARD -87 T>C (rs2016520), may play an important role in regulation of PPARD expression. However its expression patterns as well as contribution to colorectal cancer (CRC) are still controversial. In this study, the presence of the intratumoral heterogeneity of PPARD -87 T>C (rs2016520) polymorphism and its influence in CRC were investigated. Tumor masses from primary CRC patients were collected during the tumorectomy, specimens from different sites of the same tumor mass were sampled and stored individually. The SNP of PPARD -87 T>C was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of PPARD in vivo was observed by immunohistochemistry. The correlation of PPARD -87 T>C intratumoral polymorphism and the clinicopathological parameters of patients was analyzed statistically. Tumor samples were collected from 106 CRC patients (70 males and 36 females) with an average age of 61.04±13.67 years. A total number of 808 samples (7.60±1.60 per patient) were mainly harvested at peripheral superficial (n=376), central superficial (n=163), invasive front (n=112) and mesenteric cancer foci (n=42) of tumor tissues as well as cancerous adjacent mucosa (n=104). PCR-RFLP analysis showed that T/T (n=460, 56.9%) and T/C (n=334, 41.3%) were the main genotypes of -87 T>C among these samples. Furthermore, intratumoral genotype of -87 T>C was homogeneous in 90 patients and heterogeneous in other 16 patients. The intratumoral heterogeneity was related to patient age (p=0.016), tumor location (p=0.011) and the grade of differentiation (p=0.022). For patients with intratumoral heterogeneity, immunochemistry showed that the expressions of PPARD were not influenced by T/T or T/C genotypes. Intratumoral heterogeneity of PPARD -87 T>C widely existed in CRC, and associated with patient age, tumor location and differentiation. However, the immunochemistry assay revealed that there is no significant link between heterogeneity and expression of PPARD.