Machine learning determines stemness associated with simple and basal-like canine mammary carcinomas

Author(s)

Xavier, Pedro L. P. ; Marcao, Maycon ; Simoes, Renan L. S. ; Job, Maria Eduarda G. ; Strefezzi, Ricardo de Francisco ; Fukumasu, Heidge ; Malta, Tathiane M.

• Document type: Journal article
• Source: HELIYON; v. 10, n. 5, p. 12-pg., 2024-02-28.

Abstract

Simple and complex carcinomas are the most common type of malignant Canine Mammary Tumors (CMTs), with simple carcinomas exhibiting aggressive behavior and poorer prognostic. Stemness is an ability associated with cancer initiation, malignancy, and therapeutic resistance, but is still few elucidated in canine mammary tumor subtypes. Here, we first validated, using CMT samples, a previously published canine one-class logistic regression machine learning algorithm (OCLR) to predict stemness (mRNAsi) in canine cancer cells. Then, using the canine mRNAsi, we observed that simple carcinomas exhibit higher stemness than complex carcinomas and other histological subtypes. Also, we confirmed that stemness is higher and associated with basal-like CMTs and with NMF2 metagene signature, a tumor-specific DNA-repair metagene signature. Using correlation analysis, we selected the top 50 genes correlated with higher stemness, and the top 50 genes correlated with lower stemness and further performed a gene set enrichment analysis to observe the biological processes enriched for these genes. Finally, we suggested two promise stemness-associated targets in CMTs, POLA2 and APEX1, especially in simple carcinomas. Thus, our work elucidates stemness as a potential mechanism behind the aggressiveness and development of canine mammary tumors, especially in simple carcinomas, describing evidence of a promising strategy to target this disease. (AU)

• FAPESP's process: 23/07358-0 - Establishment and Characterization of PDAC 3D spheroids in 384-well Ultra-Low Attachment plates
• Grantee: Maria Eduarda Goes Job
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/00583-0 - Integrative epigenomic analysis of gliomas: defining regulatory regions associated with stemness and with the hypermethylator phenotype of IDH1/2 mutant tumors
• Grantee: Tathiane Maistro Malta Pereira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 23/05099-7 - Identifying new therapeutic targets in Pancreatic Ductal Adenocarcinoma by combining relevant models and approaches
• Grantee: Pedro Luiz Porfirio Xavier
• Support Opportunities: Scholarships in Brazil - Generation Project
• FAPESP's process: 22/06305-7 - Identifying new therapeutic targets in Pancreatic Ductal Adenocarcinoma by combining relevant models and approaches
• Grantee: Pedro Luiz Porfirio Xavier
• Support Opportunities: Generation Project Research Grant
• FAPESP's process: 19/14928-1 - Integrative epigenomic analysis of gliomas - defining regulatory regions associated with stemness and with the hypermethylator phenotype of IDH1/2 mutant tumors
• Grantee: Tathiane Maistro Malta Pereira
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 22/09378-5 - Development of innovative therapies and diagnostic tools for veterinary oncology
• Grantee: Heidge Fukumasu
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/00283-9 - Mapping tumor epigenomic signatures in gliomas: correlating glioma stem cells with clinical and molecular data
• Grantee: Maycon Marção
• Support Opportunities: Scholarships in Brazil - Master