A bioinformatics analysis of P2RY8 expression in hepatocellular carcinoma and its clinical significance

Ruqi MEI; Qian JU; Yueping LI; Chengcong LIU

doi:10.3969/j.issn.1001-5256.2022.08.020

Volume 38 Issue 8

Aug. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(8): 1825-1833

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A bioinformatics analysis of P2RY8 expression in hepatocellular carcinoma and its clinical significance

DOI: 10.3969/j.issn.1001-5256.2022.08.020

1.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
2.
Department of Gastrointestinal Surgery, Qingdao Central Hospital, Qingdao, Shandong 266000, China

Research funding:

People's Livelihood Science and Technology Project of Qingdao (15-9-2-80-nsh);

Traditional Chinese Medicine Scientific Research Project of Qingdao in 2020 (2020-zyy026)

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Corresponding author: LIU Chengcong, 84285161@163.com(ORCID: 0000-0001-7399-3312)
Received Date: 2022-04-27
Accepted Date: 2022-05-28
Published Date: 2022-08-20

Abstract

Abstract

Objective To investigate the application value of the human B cell-confinement receptor P2RY8 in the diagnosis and prognosis of hepatocellular carcinoma (HCC) and its association with tumor immunity. Methods The Cancer Genome Atlas database was used to compare the expression of P2RY8. R software package was used to analyze the correlation between P2RY8 and tumor staging, and the receiver operating characteristic (ROC) curve and a nomogram model were established for diagnosis and survival. Tumor Immune Evaluation Resource was used to analyze immune cell infiltration, immune cell biomarkers, and immune checkpoints. STRING database was used to analyze protein-protein interaction network information. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the function of P2RY8 and its interacting genes. For the purpose of validation, HCC tissue samples were collected from 64 patients who underwent radical surgery for HCC from June 2007 to November 2008, and the corresponding adjacent tissue samples were collected from 35 patients out of these patients (tissue chips were purchased from Shanghai Outdo Biotech Co., Ltd.); related clinical data and follow-up data were analyzed, and immunohistochemistry was used to measure the expression of P2RY8 in HCC and adjacent tissue samples. The t-test was used for comparison of normally distributed continuous data between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between two variables. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used to calculate survival rates. Results P2RY8 was overexpressed in HCC, and the expression level of P2RY8 could accurately differentiate tumor from normal tissue, with an area under the ROC curve of 0.794. The patients with a higher expression level of P2RY8 tended to have a better prognosis (P=0.005). The data from 64 clinical samples also confirmed that compared with the patients with a low expression level of P2RY8, the patients with a high expression level of P2RY8 had significantly higher 3-year survival rate (78.9% vs 46.2%, P=0.007), 5-year survival rate (76.3% vs 38.5%, P=0.002), and overall survival time [92.5 (48.8-102.0) months vs 33.0 (25.0-95.5) months, P=0.022], and the Kaplan-Meier survival curve further indicated that the expression level of P2RY8 was associated with the prognosis of HCC patients. In addition, P2RY8 was positively correlated with immune cell infiltration and immune checkpoint in HCC. The GO/KEGG pathway enrichment analyses showed that P2RY8 was enriched in the signal transduction pathways such as humoral immunity and cellular immunity. Conclusion P2RY8 participates in the development, progression, and immune regulation of HCC, and therefore, P2RY8 can serves as a potential biomarker and a therapeutic target for the diagnosis and prognosis of HCC.
- Carcinoma, Hepatocellular,
- Human B cell restriction receptor P2RY8,
- TCGA,
- Biomarkers

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References

[1]	MCGLYNN KA, PETRICK JL, LONDON WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability[J]. Clin Liver Dis, 2015, 19(2): 223-238. DOI: 10.1016/j.cld.2015.01.001.
[2]	SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[3]	COURI T, PILLAI A. Goals and targets for personalized therapy for HCC[J]. Hepatol Int, 2019, 13(2): 125-137. DOI: 10.1007/s12072-018-9919-1.
[4]	KANWAL F, SINGAL AG. Surveillance for hepatocellular carcinoma: current best practice and future direction[J]. Gastroenterology, 2019, 157(1): 54-64. DOI: 10.1053/j.gastro.2019.02.049.
[5]	KIRKIN V, DIKIC I. Ubiquitin networks in cancer[J]. Curr Opin Genet Dev, 2011, 21(1): 21-28. DOI: 10.1016/j.gde.2010.10.004.
[6]	TANDON P, GARCIA-TSAO G. Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies[J]. Liver Int, 2009, 29(4): 502-510. DOI: 10.1111/j.1478-3231.2008.01957.x.
[7]	EL-KHOUEIRY AB, SANGRO B, YAU T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017, 389(10088): 2492-2502. DOI: 10.1016/S0140-6736(17)31046-2.
[8]	YAU T, PARK JW, FINN RS, et al. CheckMate 459: A randomized, multi-center phase Ⅲ study of nivolumab (NⅣO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC)[J]. Ann Oncol, 2019, 30(5_suppl): 874-875. DOI: 10.1093/annonc/mdz394.029.
[9]	FINN RS, RYOO BY, MERLE P, et al. Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC)[J]. J Clin Oncol, 2019, 37(15_suppl): 4004. DOI: 10.1200/JCO.2019.37.15_suppl.4004.
[10]	SCHMITZ R, WRIGHT GW, HUANG DW, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma[J]. N Engl J Med, 2018, 378(15): 1396-1407. DOI: 10.1056/NEJMoa1801445.
[11]	MUPPIDI JR, SCHMITZ R, GREEN JA, et al. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma[J]. Nature, 2014, 516(7530): 254-258. DOI: 10.1038/nature13765.
[12]	MUPPIDI JR, LU E, CYSTER JG. The G protein-coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination[J]. J Exp Med, 2015, 212(13): 2213-2222. DOI: 10.1084/jem.20151250.
[13]	LU E, WOLFREYS FD, MUPPIDI JR, et al. S-Geranylgeranyl-L-glutathione is a ligand for human B cell-confinement receptor P2RY8[J]. Nature, 2019, 567(7747): 244-248. DOI: 10.1038/s41586-019-1003-z.
[14]	PAGE EC, HEATLEY SL, EADIE LN, et al. HMGN1 plays a significant role in CRLF2 driven down syndrome leukemia and provides a potential therapeutic target in this high-risk cohort[J]. Oncogene, 2022, 41(6): 797-808. DOI: 10.1038/s41388-021-02126-4.
[15]	AYPAR U, TAYLOR J, GARCIA JS, et al. P2RY8-CRLF2 fusion-positive acute myeloid leukemia with myelodysplasia-related changes: response to novel therapy[J]. JCO Precis Oncol, 2020, 4: 152-160. DOI: 10.1200/PO.19.00294.
[16]	TOMCZAK K, CZERWIŃSKA P, WIZNEROWICZ M. The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge[J]. Contemp Oncol (Pozn), 2015, 19(1A): A68-A77. DOI: 10.5114/wo.2014.47136.
[17]	RAVI R, NOONAN KA, PHAM V, et al. Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy[J]. Nat Commun, 2018, 9(1): 741. DOI: 10.1038/s41467-017-02696-6.
[18]	JIANG P, GU S, PAN D, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response[J]. Nat Med, 2018, 24(10): 1550-1558. DOI: 10.1038/s41591-018-0136-1.
[19]	HE Y, GALLMAN AE, XIE C, et al. P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance[J]. J Exp Med, 2022, 219(1): 7-33. DOI: 10.1084/jem.20211004.
[20]	GREAVES SA, PETERSON JN, STRAUCH P, et al. Active PI3K abrogates central tolerance in high-avidity autoreactive B cells[J]. J Exp Med, 2019, 216(5): 1135-1153. DOI: 10.1084/jem.20181652.
[21]	BOUMA G, BURNS SO, THRASHER AJ. Wiskott-Aldrich Syndrome: Immunodeficiency resulting from defective cell migration and impaired immunostimulatory activation[J]. Immunobiology, 2009, 214(9-10): 778-790. DOI: 10.1016/j.imbio.2009.06.009.
[22]	BOURNAZOS S, CORTI D, VIRGIN HW, et al. Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection[J]. Nature, 2020, 588(7838): 485-490. DOI: 10.1038/s41586-020-2838-z.

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A bioinformatics analysis of P2RY8 expression in hepatocellular carcinoma and its clinical significance

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