RECK gene polymorphism in patients with hepatocellular carcinoma

Background: Liver cancer is the sixth most common cancer and the third cause of cancer related deaths. In Egypt, hepatocellular carcinoma (HCC) has become the second most prevalent cancer among men. Gene and protein expression profiling will allow better screening of different stages of HCC as well as establishment of criteria for targeted therapies. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene against activated oncogenes. Downregulation of RECK is documented in a wide range of malignant neoplasms and correlates with poor prognosis and tumor metastasis. The aim of this work was to study the association between RECK gene polymorphism and the development of hepatocellular carcinoma in patients with liver cirrhosis. Methods: This study was conducted on 115 individuals; 47 patients with HCC, 48 patients with cirrhosis without HCC, and 20 healthy volunteers as controls. For all groups, clinical data and image findings were studied as well as laboratory investigations mainly alpha fetoprotein assay by enzyme immunoassay (ELISA) and RECK gene rs10814325 using PCR-RFLP analysis. Tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. Results: HCC is more prevalent (55.3%) in mutant RECK genotypes (T/C and C/C) than the wild RECK genotype T/T (44.7%). In Child A class, the wild T/T group was significantly higher than the mutant T/C group (p = 0.04). The mean value of MELD score in the mutant genotype T/C was significantly higher than that of the wild type T/T and the mutant type C/C (p = 0.03). In Okuda stage 1, a significant difference was found between the wild T/T and the mutant C/C groups, also between the mutant T/C and the mutant C/C groups. RECK gene polymorphism analysis using ROC curve in HCC patients and healthy controls yields low sensitivity result (55.3%), high specificity (95%), and an AUC of 0.752. RECK gene polymorphism analysis using ROC curve in HCC and cirrhosis patients yields a low sensitivity (55.3%), moderate specificity (77.1%), and an AUC of 0.664. Conclusions: RECK gene rs10814325 is associated with higher HCC susceptibility.