AccScience Publishing / TD / Online First / DOI: 10.36922/td.3469
ORIGINAL RESEARCH ARTICLE

The role of pyroptosis-related genes in breast cancer progression

Shanshan Wang1† Dashuang Yang2† Jiaqian Mo1 Moxian Chen3 Rongxin Zhang1*
Show Less
1 Department of Life Sciences and Biopharmaceutics, Guang Dong Pharmaceutical University, Guangzhou, Guangdong, China
2 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong, China
3 State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China and College of Life Sciences, Nanjing Forestry University, Nanjing, Jiangsu, China
Tumor Discovery 2024, 3(3), 3469 https://doi.org/10.36922/td.3469
Submitted: 23 April 2024 | Accepted: 19 August 2024 | Published: 24 September 2024
© 2024 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Breast cancer (BC) is one of the most common malignant cancers affecting females worldwide. Pyroptosis, a form of programmed cell death associated with inflammation and triggered by pro-inflammatory signals, is not well understood in the context of BC. This study aimed to investigate the role of pyroptosis in BC patients. Paired tumor and adjacent normal tissue samples were obtained from The Cancer Genome Atlas. Using a least absolute shrinkage and selection operator Cox analysis, we identified 15 prognostic genes associated with BC. Among these, fibrinogen C domain-containing 1, calcium voltage-gated channel subunit alpha1 H, heat shock protein family B (small) member 8, and peroxidasin-like (PXDNL) were classified as high-risk genes in BC. In contrast, the remaining 11 genes, such as proteasome activator subunit 2 and DIRAS (DIRAS family GTPase 3), were low-risk genes. Kyoto Encyclopedia of Genes and Genomes and Gene ontology analyses revealed that immune-related genes were enriched but showed reduced immunological status in the high-risk group, indicating that pro-inflammatory factors and immune antigens were produced during cell death. Consequently, targeting immune antigens with new immunosuppressants may offer a novel approach to treating BC. Moreover, the expression levels of the prognostic genes PXDNL, armadillo-like helical domain-containing 1 (ARMH1), APOBEC3D, and APOBEC3F in BC cell lines were assessed using quantitative polymerase chain reaction and western blotting. PXDNL and ARMH1 exhibited high levels of expression in BC, suggesting they could be potential therapeutic targets.

Keywords
Breast cancer
Pyroptosis
Inflammation
Prognostic genes
The cancer genome atlas
Funding
This work was supported by the Administration of Traditional Chinese Medicine of Guangdong Province (No. 20221218).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflicts of interest.
References

1. Nolan E, Lindeman GJ, Visvader JE. Deciphering breast cancer: From biology to the clinic. Cell. 2023;186(8): 1708-1728. doi: 10.1016/j.cell.2023.01.040

 

2. Ye F, Dewanjee S, Li Y, et al. Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer. Mol Cancer. 2023;22(1):105. doi: 10.1186/s12943-023-01805-y

 

3. Breast Cancer. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer [Last accessed on 2024 Feb 21].

 

4. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204-1222. doi: 10.1016/S0140-6736(20)30925-9

 

5. Zhou Z, He H, Wang K, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science. 2020;368(6494):eaaz7548. doi: 10.1126/science.aaz7548

 

6. Xing Y, Zhang F, Ji P, et al. Efficient delivery of GSDMD-N mRNA by engineered extracellular vesicles induces pyroptosis for enhanced immunotherapy. Small. 2023;19(20):2204031. doi: 10.1002/smll.202204031

 

7. Newton K, Strasser A, Kayagaki N, Dixit VM. Cell death. Cell. 2024;187(2):235-256. doi: 10.1016/j.cell.2023.11.044

 

8. Guo X, Bian Y, Zhang Y, Yu H, Yu X. Research progress of mechanism of non-coding RNA-regulated pyroptosis in atherosclerosis. Pract J Card Cereb Pneumal Vasc Dis. 2021;29(12):136-140.

 

9. Tsuchiya K. Inflammasome-associated cell death: Pyroptosis, apoptosis, and physiological implications. Microbiol Immunol. 2020;64(4):252-269. doi: 10.1111/1348-0421.12771

 

10. Chen C, Ye Q, Wang L, et al. Targeting pyroptosis in breast cancer: Biological functions and therapeutic potentials on It. Cell Death Discov. 2023;9:75. doi: 10.1038/s41420-023-01370-9

 

11. Wang Y, Sun M, Liu J, et al. FIBCD1 overexpression predicts poor prognosis in patients with hepatocellular carcinoma. Oncol Lett. 2020;19(1):795-804. doi: 10.3892/ol.2019.11183

 

12. Vishnubalaji R, Alajez NM. Epigenetic regulation of triple negative breast cancer (TNBC) by TGF-β signaling. Sci Rep. 2021;11(1):15410. doi: 10.1038/s41598-021-94514-9

 

13. Li S, Hao M, Li B, et al. CACNA1H downregulation induces skeletal muscle atrophy involving endoplasmic reticulum stress activation and autophagy flux blockade. Cell Death Dis. 2020;11(4):279. doi: 10.1038/s41419-020-2484-2

 

14. Sharma S, Wu SY, Jimenez H, et al. Ca2+ and CACNA1H mediate targeted suppression of breast cancer brain metastasis by AM RF EMF. EBioMedicine. 2019;44:194-208. doi: 10.1016/j.ebiom.2019.05.038

 

15. Nanba K, Blinder AR, Rege J, et al. Somatic CACNA1H mutation as a cause of aldosterone-producing adenoma. Hypertens Dallas Tex 1979. 2020;75(3):645-649. doi: 10.1161/HYPERTENSIONAHA.119.14349

 

16. Bildik G, Liang X, Sutton MN, Bast RC, Lu Z. DIRAS3: An imprinted tumor suppressor gene that regulates RAS and PI3K-driven cancer growth, motility, autophagy, and tumor dormancy. Mol Cancer Ther. 2022;21(1):25-37. doi: 10.1158/1535-7163.MCT-21-0331

 

17. Li H, Yang L, Fu H, et al. Association between Gαi2 and ELMO1/Dock180 connects chemokine signalling with Rac activation and metastasis. Nat Commun. 2013;4:1706. doi: 10.1038/ncomms2680

 

18. Yuan JQ, Zhang KJ, Wang SM, Guo L. YAP1/MMP7/CXCL16 axis affects efficacy of neoadjuvant chemotherapy via tumor environment immunosuppression in triple-negative breast cancer. Gland Surg. 2021;10(9):2799-2814. doi: 10.21037/gs-21-612

 

19. Sizemore ST, Sizemore GM, Booth CN, et al. Hypomethylation of the MMP7 promoter and increased expression of MMP7 distinguishes the basal-like breast cancer subtype from other triple-negative tumors. Breast Cancer Res Treat. 2014;146(1):25-40. doi: 10.1007/s10549-014-2989-4

 

20. Zhang Z, Yang M, Chen R, et al. IBP regulates epithelial-to-mesenchymal transition and the motility of breast cancer cells via Rac1, RhoA and Cdc42 signaling pathways. Oncogene. 2014;33(26):3374-3382. doi: 10.1038/onc.2013.337

 

21. Bougeret C, Jiang S, Keydar I, Avraham H. Functional analysis of Csk and CHK kinases in breast cancer cells. J Biol Chem. 2001;276(36):33711-33720. doi: 10.1074/jbc.M104209200

 

22. Kim S, Zagozdzon R, Meisler A, et al. Csk homologous kinase (CHK) and ErbB-2 interactions are directly coupled with CHK negative growth regulatory function in breast cancer. J Biol Chem. 2002;277(39):36465-36470. doi: 10.1074/jbc.M206018200

 

23. Ranzato E, Martinotti S, Magnelli V, et al. Epigallocatechin- 3-gallate induces mesothelioma cell death via H2O2- dependent T-type Ca2+ channel opening. J Cell Mol Med. 2012;16(11):2667-2678. doi: 10.1111/j.1582-4934.2012.01584.x

 

24. Ohkubo T, Yamazaki J. T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells. Int J Oncol. 2012;41(1):267-275. doi: 10.3892/ijo.2012.1422

 

25. Maiques O, Macià A, Moreno S, et al. Immunohistochemical analysis of T-type calcium channels in acquired melanocytic naevi and melanoma. Br J Dermatol. 2017;176(5): 1247-1258. doi: 10.1111/bjd.15121

 

26. Cristofani R, Piccolella M, Crippa V, et al. The role of HSPB8, a component of the chaperone-assisted selective autophagy machinery, in cancer. Cells. 2021;10(2):335. doi: 10.3390/cells10020335

 

27. Lackey L, Law EK, Brown WL, Harris RS. Subcellular localization of the APOBEC3 proteins during mitosis and implications for genomic DNA deamination. Cell Cycle Georget Tex. 2013;12(5):762-772. doi: 10.4161/cc.23713

 

28. Huang D, Chen X, Zeng X, et al. Targeting regulator of G protein signaling 1 in tumor-specific T cells enhances their trafficking to breast cancer. Nat Immunol. 2021;22(7): 865-879. doi: 10.1038/s41590-021-00939-9

 

29. Li Y, Jiao Y, Luo Z, Li Y, Liu Y. High peroxidasin-like expression is a potential and independent prognostic biomarker in breast cancer. Medicine (Baltimore). 2019;98(44):e17703. doi: 10.1097/MD.0000000000017703

 

30. Revathidevi S, Murugan AK, Nakaoka H, Inoue I, Munirajan AK. APOBEC: A molecular driver in cervical cancer pathogenesis. Cancer Lett. 2021;496:104-116. doi: 10.1016/j.canlet.2020.10.004

 

31. Shen B, Chapman JH, Custance MF, Tricola GM, Jones CE, Furano AV. Perturbation of base excision repair sensitizes breast cancer cells to APOBEC3 deaminase-mediated mutations. Elife. 2020;9:e51605. doi: 10.7554/eLife.51605

 

32. Smith NJ, Fenton TR. The APOBEC3 genes and their role in cancer: Insights from human papillomavirus. J Mol Endocrinol. 2019;62(4):R269-R287. doi: 10.1530/JME-19-0011

 

33. Law EK, Levin-Klein R, Jarvis MC, et al. APOBEC3A catalyzes mutation and drives carcinogenesis in vivo. J Exp Med. 2020;217(12):e20200261. doi: 10.1084/jem.20200261

 

34. Burns MB, Lackey L, Carpenter MA, et al. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature. 2013;494(7437):366-370. doi: 10.1038/nature11881

 

35. Martín-Pardillos A, Cajal SRY. Characterization of Kelch domain-containing protein 7B in breast tumours and breast cancer cell lines. Oncol Lett. 2019;18(3):2853-2860. doi: 10.3892/ol.2019.10672

 

36. Zhao H, Yin X, Wang L, et al. Identifying tumour microenvironment-related signature that correlates with prognosis and immunotherapy response in breast cancer. Sci Data. 2023;10(1):119. doi: 10.1038/s41597-023-02032-2

 

37. Tian W, Luo Y, Tang Y, et al. Novel implication of the basement membrane for breast cancer outcome and immune infiltration. Int J Biol Sci. 2023;19:1645-1663. doi: 10.7150/ijbs.81939

 

38. Qi A, Ju M, Liu Y, et al. Development of a novel prognostic signature based on antigen processing and presentation in patients with breast cancer. Pathol Oncol Res. 2021;27:600727. doi: 10.3389/pore.2021.600727

 

39. Bjarnadottir O, Kimbung S, Johansson I, et al. Global transcriptional changes following statin treatment in breast cancer. Clin Cancer Res. 2015;21(15):3402-3411. doi: 10.1158/1078-0432.CCR-14-1403

 

40. Jeong G, Bae H, Jeong D, et al. A Kelch domain-containing KLHDC7B and a long non-coding RNA ST8SIA6-AS1 act oppositely on breast cancer cell proliferation via the interferon signaling pathway. Sci Rep. 2018;8(1):12922. doi: 10.1038/s41598-018-31306-8

 

41. Mumme H, Thomas BE, Bhasin SS, et al. Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia. Nat Commun. 2023;14:6209. doi: 10.1038/s41467-023-41994-043

 

42. Chen Q, Jun H, Yang C, Yang F, Xu Y. The pyroptosis-related risk genes APOBEC3D, TNFRSF14, and RAC2 were used to evaluate prognosis and as tumor suppressor genes in breast cancer. J Oncol. 2022;2022:3625790 doi: 10.1155/2022/3625790

 

43. Jia ZC, Yang X, Wu YK, et al. The art of finding the right drug target: Emerging methods and strategies. Pharmacol Rev. 2024;76:896-914. doi: 10.1124/pharmrev.123.00102844

 

44. Yang X, Li M, Jia ZC, et al. Unraveling the secrets: Evolution of resistance mediated by membrane proteins. Drug Resist Updat. 2024;77:101140. doi: 10.1016/j.drup.2024.10114045

 

45. Liu H, Chen X, Jia Y, et al. Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment. Interdiscipl Med. 2023;1:e20220013. doi: 10.1002/INMD.20220013

Share
Back to top
Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing