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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model
Hao-Ling Zhang, Sandai Doblin, Zhong-Wen Zhang, Zhi-Jing Song, Babu Dinesh, Yasser Tabana, Dahham Sabbar Saad, Mowaffaq Adam Ahmed Adam, Yong Wang, Wei Wang, Hao-Long Zhang, Sen Wu, Rui Zhao, Barakat Khaled
Hao-Ling Zhang, Sandai Doblin, Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang 13200, Malaysia
Zhong-Wen Zhang, School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Zhi-Jing Song, Rui Zhao, Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Babu Dinesh, Yasser Tabana, Barakat Khaled, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton AB T6G 2E1, Canada
Dahham Sabbar Saad, Department of Science, University of Technology and Applied Sciences Rustaq, Rustaq 10 P.C. 329, Oman
Mowaffaq Adam Ahmed Adam, Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182, United States
Yong Wang, Department of Pathology Center, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Wei Wang, College of Acupuncture-moxibustion and Tuina, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Hao-Long Zhang, Universiti Sains Malaysia, Advanced Medical and Dental Institute, Penang 13200, Malaysia
Sen Wu, Department of Biomedical Science, Universiti Sains Malaysia, Penang 13200, Malaysia
Co-corresponding authors: Sandai Doblin and Song Zhi-Jing.
Author contributions: Zhang HL was responsible for drafting the primary manuscript and conducting the data analyses; Dinesh B, Tabana Y, Saad DS, Adam Ahmed Adam M, Zhang HL, Zhao R, Barakat K, Wang Y, and Wang W were involved in the data collection, and preparation of tables and charts; Sandai D, Zhang ZW, and Song ZJ had pivotal roles in the research design, guiding the research group, and orchestrating the collaborative efforts of all authors; Sandai D and Song ZJ gave detailed guidance on the paper; All authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81960877; University Innovation Fund of Gansu Province, No. 2021A-076; Gansu Province Science and Technology Plan (Innovation Base and Talent Plan), No. 21JR7RA561; Natural Science Foundation of Gansu Province, No. 21JR1RA267 and No. 22JR5RA582; Education Technology Innovation Project of Gansu Province, No. 2022A-067; Innovation Fund of Higher Education of Gansu Province, No. 2023A-088; Gansu Province Science and Technology Plan International Cooperation Field Project, No. 23YFWA0005; and Open Project of Key Laboratory of Dunhuang Medicine and Transformation of Ministry of Education, No. DHYX21-07, No. DHYX22-05, and No. DHYX21-01.
Institutional review board statement: No experimental studies on human and animal ethics were designed in this study.
Informed consent statement: This study did not conduct clinical trials and did not involve informed consent signed by subjects and investigators.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at [doblin@usm.my]. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Sandai Doblin, PhD, Professor, Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang 13200, Malaysia. doblin@usm.my
Received: September 8, 2023
Peer-review started: September 8, 2023
First decision: November 30, 2023
Revised: December 10, 2023
Accepted: January 12, 2024
Article in press: January 12, 2024
Published online: February 24, 2024
BACKGROUND
Breast cancer is a multifaceted and formidable disease with profound public health implications. Cell demise mechanisms play a pivotal role in breast cancer pathogenesis, with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.
AIM
To investigate the impact of ATP-induced cell death (AICD) on breast cancer, enhancing our understanding of its mechanism.
METHODS
The foundational genes orchestrating AICD mechanisms were extracted from the literature, underpinning the establishment of a prognostic model. Simultaneously, a microRNA (miRNA) prognostic model was constructed that mirrored the gene-based prognostic model. Distinctions between high- and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized, with the aim of delineating common influence mechanisms, substantiated through enrichment analysis and immune infiltration assessment.
RESULTS
The mRNA prognostic model in this study encompassed four specific mRNAs: P2X purinoceptor 4, pannexin 1, caspase 7, and cyclin 2. The miRNA prognostic model integrated four pivotal miRNAs: hsa-miR-615-3p, hsa-miR-519b-3p, hsa-miR-342-3p, and hsa-miR-324-3p. B cells, CD4+ T cells, CD8+ T cells, endothelial cells, and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways, while miRNA risk scores significantly enriched 29 signaling pathways, with 16 pathways being jointly enriched.
CONCLUSION
Of paramount significance, distinct mRNA and miRNA signature models were devised tailored to AICD, both potentially autonomous prognostic factors. This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools, offering an unparalleled window for innovative interventions. Essentially, this paper reveals the hitherto enigmatic link between AICD and breast cancer, potentially leading to revolutionary progress in personalized oncology.
Core Tip: This study developed and validated a prognostic model based on the intricately underlying genes associated with ATP-induced cell death. At the same time, we shaped a microRNA prognostic model that harmonizes with a gene-centric approach. This study comprehensively elucidated the complex molecular basis of ATP-induced breast cancer cell death, which not only opens up new avenues for potential therapeutic interventions but also promotes an innovative paradigm in the field of personalized oncology. By enhancing our understanding of this complex cellular process, we anticipate that our research will facilitate the emergence of groundbreaking strategies that are transformative.
