Role of Interleukin-28 B Gene Polymorphism and Cytomegalovirus Coinfection in Hepatocellular Carcinoma Patients with Chronic Hepatitis C Virus

Background: Liver diseases including HCC are life-threatening morbidities. Mechanisms of HCC are still unclear. Cytomegalovirus (CMV) is DNA virus characterized by latency and cellular transformation. Genetic polymorphisms especially SNPs are the most common genetic variation. It plays a critical role in regulation of cellular interaction and cytokine production. CMV infection and its role in HCC is under investigation. Objectives: to profile IL28B single-nucleotide polymorphism in development of HCC in chronic HCV, and identify the relationship between human cytomegalovirus infection, IL28B SNPs and HCC. Methodology: 120 blood samples were obtained from HCV patients; divided according to clinical, radiological and laboratory data into three equal groups, forty patients each: HCV, HCC, LC groups, and 40 normal persons as controls. SNPs of interleukin-28 (IL28B rs12979860) by RFLP and CMV viral DNA by real-time polymerase chain reaction were investigated. Results: IL28B /CC genotype was increased significantly in controls and TT genotype in HCC group. A positive correlation among HCV viral load, CMV with the genotype IL28B rs12979860/TT especially in HCC group. Conclusions: IL28B rs12979860/TT is expressed in HCC patients making its role in development of HCC in CMV positive HCV patients cannot be denied.

Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer

Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rates in bone. Acquired resistance to apoptosis is PCa cell intrinsic, and is associated with a shift in IL-28Rα signaling via STAT1 to STAT3. Notably, STAT3 ablation or inhibition impairs MSC-selected prostate cancer cell growth and survival. Thus, bone marrow MSCs drive the emergence of therapy-resistant bone metastatic prostate cancer yet this can be disabled by targeting STAT3.

Correlation between interleukin-28 gene polymorphism with interleukin-28 cytokine levels and viral genotypes among HCV patients in Yazd, Iran

Objectives Recent studies using genome-wide association studies (GWAS) have shown the strong association between polymorphisms near the interleukin-28B (IL-28B) gene and spontaneous clearance of hepatitis C virus (HCV). The present study was designed to evaluate the association of interleukin-28 gene polymorphism with interleukin-28 cytokine levels in different viral genotypes among HCV patients in Yazd, Iran. Result The most prevalent genotype in chronic cases was genotype 3a, and the lowest one was 2/3a. There were statistically significant differences in genotype frequency between the two studied groups for IL-28B rs12979860C/T. The frequency of CC genotype of IL-28B at rs12979860 SNP was higher in spontaneously cleared patients in comparison with chronic HCV patients. Significant association was found when serum levels of IL28B were compared to various IL-28 genotypes. There was a significant difference between IL-28 polymorphism and HCV genotypes (p = 0.003).