AUTHOR=Wang Jian , Jiang Haiming 

TITLE=A novel mitochondrial function-associated programmed cell death-related prognostic signature for predicting the prognosis of early breast cancer

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1406426

DOI=10.3389/fgene.2024.1406426

ISSN=1664-8021

ABSTRACT=<p><bold>Purpose:</bold> To screen mitochondrial function-associated PCD-related biomarkers and construct a risk model for predicting the prognosis of early breast cancer.</p><p><bold>Methods:</bold> Data on gene expression levels and clinical information were obtained from the TCGA database, and GSE42568 and GSE58812 datasets were obtained from GEO database. The mitochondrial function-associated programmed cell death (PCD) related genes in early breast cancer were identified, then LASSO logistic regression, SVM-RFE, random forest (RF), and multiple Cox logistic regression analysis were employed to construct a prognostic risk model. Differences in immune infiltration, drug sensitivity, and immunotherapy response were evaluated between groups. Lastly, the qRT-PCR was employed to confirm the key genes.</p><p><bold>Results:</bold> Total 1,478 DEGs were screened between normal and early breast cancer groups, and these DEGs were involved in PI3K-Akt signaling pathway, focal adhesion, and ECM-receptor interaction pathways. Then total 178 mitochondrial function-associated PCD related genes were obtained, followed by a four mitochondrial function-associated PCD related genes prognostic model and nomogram were built. In addition, total 2 immune checkpoint genes were lowly expressed in the high-risk group, including CD47 and LAG3, and the fraction of some immune cells in high- and low-risk groups had significant difference, such as macrophage, eosinophil, mast cell, etc., and the Top3 chemotherapeutics with significant differences were included FH535, MK.2206, and bicalutamide. Finally, the qRT-qPCR results shown that the CREB3L1, CAPG, SPINT1 and GRK3 mRNA expression were in line with the bioinformatics analysis results.</p><p><bold>Conclusion:</bold> Four mitochondrial function-associated PCD-related genes were identified, including CREB3L1, CAPG, SPINT1, and GRK3, and the prognostic risk model and nomogram were established for predicting the survival of early breast cancer patient. The chemotherapeutics, containing FH535, MK.2206, and bicalutamide, might be used for early breast cancer.</p>