Role of purinergic receptors in hepatobiliary carcinoma in Pakistani population: an approach towards proinflammatory role of P2X4 and P2X7 receptors

Abstract

The primary malignancy of liver, known as hepatocellular carcinoma (HCC), comprises 9% of all hepatobiliary carcinomas. A steady rise has also been observed in adenocarcinoma (ADC) of the liver and ampullary carcinoma (AMC), ascending to 0.5% of gastrointestinal malignancies. Hepatobiliary carcinomas consist of 13% of all cancer occurrences worldwide. Purinergic receptor-based signaling holds the therapeutic potential based on its role in cell proliferation of several carcinomas. An altered ATP concentration in nanomoles may lead towards crucial changes in cancer growth patterns in liver tissue. A total of 40 tissue samples were collected (20 samples of HCC, 10 samples of ADC, and 10 samples of AMC) from patients that underwent surgery. P2X4 and P2X7 receptors exhibited significantly increased expression in HCC, ADC, and AMC samples as compared with the control tissue samples. While ADC and AMC samples showed higher expression of P2X4 and P2X7 than the control, statistically, HCC samples exhibited the most significant expression of both P2X4 and P2X7 receptors than control tissues. It may be inferred that higher expression of P2X4 and P2X7 receptors is significantly associated with the upregulated cellular stress leading to inflammation and it is plausible that both these receptors may be used in diagnostic, prognostic, and therapeutic tools for carcinoma studies in the future.

An Inflammatory Response-Related Gene Signature Can Impact the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma

“…MEP1A has been explored as a prognostic marker for patients with HCC, especially early HCC, and it may play an important role in the progression of HCC by promoting migration and invasion of cancer cells ( 30 ). P2X4 receptor may be closely related to the downstream inflammatory process by activation of oxidative stress, inflammasome, and immune modulation for continuous cancer progression ( 31 ). Arun Asif et al demonstrated that increased RIPK2 activity leads to the activation of NF-κB, which up-regulates the proliferation, invasion, metastasis and anti-apoptosis of cancer cells ( 32 ).…”

P2X7 Variants in Oncogenesis

“…Interestingly, an antibody directed against nfP2X7 also proved efficacious in reducing basal cell carcinoma growth in a phase I clinical trial on humans [83]. These data are of sure relevance to develop new P2X7-targeting therapies, also considering that an increasing number of studies report an association between P2X7 overexpression and bad prognosis or response to therapy in oncologic patients [42,65,72,[84][85][86][87]. The majority of these studies do not take into account known P2X7 variants, but some interesting progress was made in this field of research in last years that we cover in the present overview.…”

Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target

“…P2X4R are also expressed in many cancer types, including lung, colorectal, bladder cancer, leukaemia, brain tumour, and, most importantly to this study, PCa [ 19 ]. Functionally, most studies suggest that P2X4R positively associates with tumourigenesis [ 20 , 21 , 22 ]. However, whether and how P2X4R is involved in PCa progression remains to be elucidated.…”