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Machine learning determines stemness associated with simple and basal-like canine mammary carcinomas
Pedro L P Xavier1, Maycon Marção2, Renan L S Simões2
1Laboratory of Comparative and Translational Oncology (LOCT), Department of Veterinary Medicine, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, São Paulo, Brazil.
Heliyon
|March 5, 2024
Summary
This study reveals that canine mammary tumors with simple carcinomas show higher stemness, a trait linked to cancer aggressiveness. Researchers identified potential therapeutic targets, POLA2 and APEX1, for these aggressive tumors.
Area of Science:
- Veterinary Oncology
- Cancer Stem Cell Biology
- Canine Mammary Tumors (CMTs)
Background:
- Simple carcinomas are aggressive malignant Canine Mammary Tumors (CMTs) with poor prognosis.
- Cancer stemness contributes to tumor initiation, malignancy, and treatment resistance, but its role in CMT subtypes is unclear.
Purpose of the Study:
- To validate a machine learning algorithm for predicting stemness in canine cancer cells.
- To investigate stemness levels across different canine mammary tumor subtypes.
- To identify potential therapeutic targets associated with stemness in CMTs.
Main Methods:
- Validated a canine one-class logistic regression (OCLR) algorithm to predict stemness (mRNAsi) in CMT samples.
- Analyzed stemness levels in relation to histological subtypes, basal-like characteristics, and the NMF2 metagene signature.
- Performed correlation analysis to identify genes associated with high and low stemness, followed by gene set enrichment analysis.
Main Results:
- Simple carcinomas exhibited significantly higher stemness (mRNAsi) compared to complex carcinomas and other CMT subtypes.
- Elevated stemness was associated with basal-like CMTs and the NMF2 DNA-repair metagene signature.
- Identified POLA2 and APEX1 as promising stemness-associated targets, particularly in simple carcinomas.
Conclusions:
- Stemness is a key factor contributing to the aggressiveness and development of canine mammary tumors, especially simple carcinomas.
- Targeting stemness pathways presents a promising therapeutic strategy for canine mammary tumors.
- POLA2 and APEX1 are potential therapeutic targets for managing aggressive CMTs.

