Role of purinergic receptors in hepatobiliary carcinoma in Pakistani population: an approach towards proinflammatory role of P2X4 and P2X7 receptors
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.
KeywordsInflammatory precursor Purinergic signaling Hepatocellular carcinoma Cancer microenvironment
We are thankful to the Higher Education Commission and NUST for providing the opportunity to conduct this research work. We are also thankful to Liver Transplant Unit of Shaikh Zayd Hospital, Lahore, in coordinating this research work.
Compliance with ethical standards
The designed study was duly reviewed and approved by the ethics committee of Shaikh Zayd Hospital, Lahore, and Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, in accordance with the recommendations of the World Medical Association’s Declaration of Helsinki for biomedical experimentation involving human subjects.
Conflict of interest
Arun Asif declares that he has no conflict of interest.
Madiha Khalid declares that she has no conflict of interest.
Sobia Manzoor declares that she has no conflict of interest.
Hassam Ahmad declares that he has no conflict of interest.
Aman-ur-Rehman declares that he has no conflict of interest.
Research involving human participants and/or animals
This article involved liver biopsy samples from human participants, and does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
- 3.Teng Y, Radde BN, Litchfield LM, Ivanova MM, Prough RA, Clark BJ, Doll MA, Hein DW, Klinge CM (2015) Dehydroepiandrosterone activation of G-protein-coupled estrogen receptor rapidly stimulates microRNA-21 transcription in human hepatocellular carcinoma cells. J Biol Chem 290(25):15799–15811CrossRefGoogle Scholar
- 5.Burnstock G (2006) Purinergic signalling. Br J Pharmacol 147(S1)Google Scholar
- 15.Greve A-S, Skals M, Fagerberg SK, Tonnus W, Ellermann-Eriksen S, Evans RJ, Linkermann A, Praetorius HA (2017) P2X1, P2X4, and P2X7 receptor knock out mice expose differential outcome of sepsis induced by α-haemolysin producing Escherichia coli. Front Cell Infect Microbiol 7Google Scholar
- 17.Khalid M, Brisson L, Tariq M, Hao Y, Guibon R, Fromont G, Mortadza SAS, Mousawi F, Manzoor S, Roger S (2017) Carcinoma-specific expression of P2Y11 receptor and its contribution in ATP-induced purinergic signalling and cell migration in human hepatocellular carcinoma cells. Oncotarget 8(23):37278–37290CrossRefGoogle Scholar
- 32.Csóka B, Németh ZH, Szabó I, Davies DL, Varga ZV, Pálóczi J, Falzoni S, Di Virgilio F, Muramatsu R, Yamashita T (2018) Macrophage P2X4 receptors augment bacterial killing and protect against sepsis. JCI insight 3(11)Google Scholar
- 33.Hofman P, Cherfils-Vicini J, Bazin M, Ilie M, Juhel T, Hébuterne X, Gilson E, Schmid-Allilana A, Boyer O, Adriouch S (2015) Genetic and pharmacological inactivation of the purinergic P2RX7 receptor dampens inflammation but increases tumor incidence in a mouse model of colitis-associated cancer. Cancer Res Canres 1778.2014Google Scholar
- 35.Khalid M, Manzoor S, Ahmad H, Asif A, Bangash TA, Latif A, Jaleel S (2018) Purinoceptor expression in hepatocellular virus (HCV)-induced and non-HCV hepatocellular carcinoma: an insight into the proviral role of the P2X4 receptor. Mol Biol Rep 1–6Google Scholar
- 36.Huang C-F, Yeh M-L, Tsai P-C, Hsieh M-H, Yang H-L, Hsieh M-Y, Yang J-F, Lin Z-Y, Chen S-C, Wang L-Y (2014) Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication. J Hepatol 61(1):67–74CrossRefGoogle Scholar