A single nucleotide polymorphism in EZH2 predicts overall survival rate in patients with cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is a deadly disease arising from the malignant transformation of cholangiocytes. Enhancer of zeste homolog 2 (EZH2) is overexpressed in poorly differentiated CCA. Functional single nucleotide polymorphisms (SNPs) in this gene may affect the role of EZH2 in cholangiocarcinogenesis and chemoresistance. The aim of the current study was to evaluate the correlation between EZH2 SNPs and clinical outcome. Using PROMO3.0, GeneCard and MicroSNiper, 4 EZH2 SNPs with functional relevance in CCA were selected in silico. These SNPs were studied in genomic DNA extracted from the blood samples of 75 patients with advanced CCA, who were treated with epirubicin-cisplatin-xeloda (ECX regimen). SNP genotyping was performed with specific PCR assays. The rs887569 TT genotype was correlated with a significantly longer overall survival (OS; TT vs. CT-CC, P=0.026). Moreover, the TT genotype revealed a trend toward a significant association with a reduced risk of mortality (HR, 0.59; 95% CI, 0.33–1.05; P=0.075), by multivariate analysis. These results support future studies on the role of rs887569 EZH2 SNP as a possible predictive marker of OS in advanced CCA patients.

Molecular perturbations in cholangiocarcinoma: Is it time for precision medicine?

“…13 Although two of the selected variants (rs2143417 and rs689466) in cyclooxygenase 2 (COX2) were associated with the risk of CCA in the discovery cohort (P = 0.0003 and P = 0.005 respectively), these associations failed to reach significance in the validation cohort (P > 0.05), making the results difficult to interpret. In turn, Fingas variants, enhancer of zeste homolog 2 (EZH2) (rs24179546 15 ), nuclear factor (erythroid derived 2)-like 2 (NRF2), 16 x-ray repair crosscomplementing group (XRCC1), 17 ATP binding cassette subfamily C member 2) (ABCB2), 18 ATPase Phospholipid Transporting 8B1 (ATP8B1), 19 natural killer cell receptor G2D (NKG2D), 20 or alpha1antitrypsin (α1AT) deficiency Z heterozygosity, 21 have been linked to increased risk of CCA (Table 1) detect the risk variant and later to replicate the genetic findings.…”

Elevated expression of a pharmacologic Polycomb signature predicts poor prognosis in gastric and breast cancer

“…In a number of tumor types, EZH2 is overexpressed and its elevated expression correlates with metastatic spreading and poor patient prognosis [12][13][14]. Moreover, single nucleotide polymorphisms (SNPs) present in the EZH2 gene have been associated with survival and drug response in different cancer types [15,16]. In line with these findings, pharmacologic inhibition of EZH2 decreased proliferation, tumorigenicity, and invasion while inducing apoptosis in vitro and in vivo [8,17].…”

EZH2 Single Nucleotide Variants (SNVs): Diagnostic and Prognostic Role in 10 Solid Tumor Types

“…For example, the G allele of rs2302427 has been associated with lower tumor stage in UCC patients [29]. The rs887569 TT genotype was correlated with a significantly longer OS in gallbladder cancer patients, [36] (Table 2).…”