LASSO Based Analysis for Prediction of Prognostic Signature Genes Associated with Breast Cancer

Abstract

Background: Cancer is a genetic disease, where gene alterations play a significant role in the disease onset and pathogenesis. Analysis of the underlying gene interaction pathways could reveal new biomarkers and could also potentially help in the development of targeted drugs for therapeutics. Microarray techniques have emerged as powerful tools capable of simultaneously measuring the expression levels of thousands of genes, making them invaluable in cancer biology research. However, the processing of the resultant datasets poses significant challenges due to their high dimensionality. Also, feature extraction becomes essential to discern the crucial features within these extensive datasets. To mitigate these difficulties advanced computational techniques like Machine Learning (ML) could be instrumental. LASSO- regression-based classification is an advanced ML technique that can help in feature selection by evaluating individual parameters like genes. Methods: This study focuses on uncovering key prognostic genes for breast cancer using a combination of LASSO regression-based classifier and statistical bioinformatics models. Differentially expressed genes (DEGs) were identified using the "Limma" package in R, and significant genes were further filtered using the LASSO-based classifier significance coefficient. Genes common to both methods were considered as the focus of this study. Additionally, Protein-Protein Interaction (PPI) networks of these key genes were constructed using STRING, and hub genes, significant modules, and associated genes were identified using Cytoscape. Results: This study identified CCR8, CXCL11, CCL23, CCL24, CCL28, and CCL21 as signature prognostic genes for breast cancer, revealing a strong association between chemokines and breast cancer pathogenesis. Extensive literature searches were conducted to validate and confirm their prognostic significance in the disease. Conclusion: These findings are pivotal for enhancing our comprehension of the pathways involved in breast cancer. Additionally, they hold promise as novel biomarkers for diagnostic purposes and may also reveal significant therapeutic targets for the management of breast cancer.