Multi-omics Pan-cancer Analysis Reveals the Prognostic Values and Immunological Functions of PPA2, with a Spotlight on Breast Cancer

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Aug 23

PMID 39176095

Authors

Jia-Ning Zhang

Bei-Bei Yang

Lin-Wei Li

Hao Xu

Bin Wang

Zi-Lu Yi

Xi-Rui Zhou

Hong Liu

Affiliations

Soon will be listed here.

Abstract

Background: Recently, the role of inorganic pyrophosphatase 2 (PPA2) has been remaining merely superficial in many tumors. Hence, the aim was to analyze the potential functions of PPA2 in pan-cancer, focusing on its role in breast cancer.

Methods: A systematic pan-cancer analysis conducted primarily utilizing various open databases such as TCGA and GTEx. We explored the clinical value of PPA2 as well as various biological functions, including expression levels and subcellular localization, multi-dimensional immune-correlation analysis, co-expression networks, and gene heterogeneity. In addition, we not only verified the function of PPA2 through cell experiments but also analyzed PPA2 at the single-cell level and its drug sensitivity.

Results: PPA2 is abnormally expressed in various tumors, and it is mainly distributed in mitochondria. Furthermore, the indicators (OS, DSS, DFI, and PFI) of analysis hint that PPA2 exhibits significant prognostic value. At the same time, the genomic heterogeneity (including TMB, MSI, MATH, and NEO) of PPA2 in pan-cancer was analyzed. Across multiple tumors, the results showed a close correlation between PPA2 expression levels and different immune signatures (such as immune cell infiltration). All of these indicate that PPA2 could potentially be applied in the guidance of immunotherapy. We also have demonstrated that PPA2 promoted the process of breast cancer. Finally, some potential therapeutic agents (such as Fulvestrant) targeting the abnormal expression of PPA2 are revealed.

Conclusion: In conclusion, the results demonstrated the great value of PPA2 in pan-cancer research, as well as its potential as a therapeutic target for breast tumors.

References

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K . Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017; 18(11):1512-1522. DOI: 10.1016/S1470-2045(17)30604-6. View

Tian B, Pang Y, Gao Y, Meng Q, Xin L, Sun C . A pan-cancer analysis of the oncogenic role of Golgi transport 1B in human tumors. J Transl Int Med. 2023; 11(4):433-448. PMC: 10732491. DOI: 10.2478/jtim-2023-0002. View

Yuan H, Yan M, Zhang G, Liu W, Deng C, Liao G . CancerSEA: a cancer single-cell state atlas. Nucleic Acids Res. 2018; 47(D1):D900-D908. PMC: 6324047. DOI: 10.1093/nar/gky939. View

Jardim D, Goodman A, Gagliato D, Kurzrock R . The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker. Cancer Cell. 2020; 39(2):154-173. PMC: 7878292. DOI: 10.1016/j.ccell.2020.10.001. View

Vaidhya A, Ghildiyal K, Rajawat D, Nayak S, Parida S, Panigrahi M . Relevance of pharmacogenetics and pharmacogenomics in veterinary clinical practice: A review. Anim Genet. 2023; 55(1):3-19. DOI: 10.1111/age.13376. View

Li Y, Dou Y, Veiga Leprevost F, Geffen Y, Calinawan A, Aguet F . Proteogenomic data and resources for pan-cancer analysis. Cancer Cell. 2023; 41(8):1397-1406. PMC: 10506762. DOI: 10.1016/j.ccell.2023.06.009. View

Bedard P, Hyman D, Davids M, Siu L . Small molecules, big impact: 20 years of targeted therapy in oncology. Lancet. 2020; 395(10229):1078-1088. DOI: 10.1016/S0140-6736(20)30164-1. View

Cerami E, Gao J, Dogrusoz U, Gross B, Sumer S, Aksoy B . The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2(5):401-4. PMC: 3956037. DOI: 10.1158/2159-8290.CD-12-0095. View

10.

Mogi A, Kuwano H . TP53 mutations in nonsmall cell lung cancer. J Biomed Biotechnol. 2011; 2011:583929. PMC: 3035360. DOI: 10.1155/2011/583929. View

11.

Colle R, Cohen R, Cochereau D, Duval A, Lascols O, Lopez-Trabada D . Immunotherapy and patients treated for cancer with microsatellite instability. Bull Cancer. 2016; 104(1):42-51. DOI: 10.1016/j.bulcan.2016.11.006. View

12.

Pizzuti M, Tsai Y, Winders H, Bookstaver P, Al-Hasan M . Application of Precision Medicine Concepts in Ambulatory Antibiotic Management of Acute Pyelonephritis. Pharmacy (Basel). 2023; 11(6). PMC: 10661281. DOI: 10.3390/pharmacy11060169. View

13.

Xie J, Zhang J, Tian W, Zou Y, Tang Y, Zheng S . The Pan-Cancer Multi-Omics Landscape of FOXO Family Relevant to Clinical Outcome and Drug Resistance. Int J Mol Sci. 2022; 23(24). PMC: 9778770. DOI: 10.3390/ijms232415647. View

14.

Moret-Tatay I, Cerrillo E, Saez-Gonzalez E, Hervas D, Iborra M, Sandoval J . Identification of Epigenetic Methylation Signatures With Clinical Value in Crohn's Disease. Clin Transl Gastroenterol. 2019; 10(10):e00083. PMC: 6919449. DOI: 10.14309/ctg.0000000000000083. View

15.

Guimier A, Achleitner M, Moreau de Bellaing A, Edwards M, De Pontual L, Mittal K . PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families. Genet Med. 2022; 24(4):967. DOI: 10.1016/j.gim.2022.02.002. View

16.

Wahida A, Buschhorn L, Frohling S, Jost P, Schneeweiss A, Lichter P . The coming decade in precision oncology: six riddles. Nat Rev Cancer. 2022; 23(1):43-54. DOI: 10.1038/s41568-022-00529-3. View

17.

Pan S, Sun S, Liu B, Hou Y . Pan-cancer Landscape of the RUNX Protein Family Reveals their Potential as Carcinogenic Biomarkers and the Mechanisms Underlying their Action. J Transl Int Med. 2022; 10(2):156-174. PMC: 9328034. DOI: 10.2478/jtim-2022-0013. View

18.

Galluzzi L, Humeau J, Buque A, Zitvogel L, Kroemer G . Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol. 2020; 17(12):725-741. DOI: 10.1038/s41571-020-0413-z. View

19.

Malone E, Oliva M, Sabatini P, Stockley T, Siu L . Molecular profiling for precision cancer therapies. Genome Med. 2020; 12(1):8. PMC: 6961404. DOI: 10.1186/s13073-019-0703-1. View

20.

Mattiuzzi C, Lippi G . Current Cancer Epidemiology. J Epidemiol Glob Health. 2019; 9(4):217-222. PMC: 7310786. DOI: 10.2991/jegh.k.191008.001. View