Immuno-histochemical Analysis of P2X Receptors in Human Explanted Tissue Samples of Hepatocellular Carcinoma in Comparison with Adenocarcinoma and Ampullary Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is classified as a primary malignancy of hepatocytes in liver tissue. With the continuous upsurge of HCC in the previous decade, it has emerged as leading cause of cancer related deaths worldwide. The incidence of HCC is the highest in Asia, and especially in Pakistan, because of hepatitis B and hepatitis C endemics into the region. The predominant causes of HCC development include cirrhosis and chronic liver disease. Hepatocellular Adenocarcinoma (ADC) or hepatic adenoma is classified as a rare malignancy of liver caused by increased level of hormones especially estrogen. Ampullary carcinoma (AMC) consists of biliary track (bile duct) carcinomas are neighboring malignancies to the liver tissue. Hepatobiliary cancers including HCC, ADC, and AMC, are most common malignancies in Pakistan consisting of 10 % of all cancers. Recently, purinergic signaling has emerged as an essential signaling mechanism to regulate inflammation. Two key receptors in purinergic signaling are P2X4 and P2X7. These are ligand-gated ion-channels to regulate Ca2+ and K+ ions influx and efflux, respectively. Growing evidence reveals their influence as pro-inflammatory receptors in cancer progression and prognosis. However, studies addressing the role of P2X4 and P2X7 receptors in hepatobiliary tissues are limited to animal models and cell lines. Keeping in view the previous studies, it was hypothesized that the prevalence of P2X4 and P2X7 receptors may have a significant role in the degree of inflammation in human liver tissue and ampullary tissue especially in the state of carcinomas. Present study aims to elucidate the pro-inflammatory role of P2X4 and P2X7 receptors in the cancer microenvironment of human liver tissues.For current study, human tissue samples of hepatocellular carcinoma, hepatic adenocarcinoma, and ampullary carcinoma patients were obtained from Hepatobiliary Unit, Shaikh Zayd Hospital Lahore, Pakistan. These tissue samples were qualitatively analyzed for the degree of P2X4 and P2X7 receptors expression. The expression of both, P2X4 and P2X7 receptors correlated well with HCC, ADC and AMC. The expression rate of both receptors particularly, P2X4 receptor was found significantly higher among all the studied cancer tissues than the normal tissues. The combined expression of these receptors indicates their essential role in inflammation in liver cancer micro-environment. Furthermore, the present study implies that P2X receptors and especially P2X4, have the potential as future biomarkers for the diagnostic, prognostic and therapeutic agents in liver tissue carcinomas.