Transcriptomic Biomarker Discovery in Drug-Resistant Breast Cancer Using TCGA RNA-seq

Overview This project investigates transcriptomic differences between drug-resistant and drug-sensitive breast cancer samples using TCGA-BRCA RNA-seq data. The objective was to identify resistance-associated biomarkers, dysregulated pathways, and clinically relevant prognostic markers.

Objectives Identify differentially expressed genes (DEGs) associated with resistance phenotype

Characterize enriched biological pathways underlying resistance

Cross-validate pathway findings using multiple enrichment strategies

Assess prognostic relevance of top resistance-associated genes

Methods Data Source: TCGA-BRCA RNA-seq via TCGAbiolinks

Differential Expression: DESeq2

Functional Enrichment: GO, KEGG GSEA, Hallmark GSEA

Cross-Validation: Enrichr

Survival Analysis: Kaplan–Meier + Cox Regression

Visualization: Volcano plots, heatmaps, enrichment dotplots, KM curves

Key Findings Identified 4,507 significant DEGs associated with resistance

Resistant tumors showed enrichment of:

Cell Cycle

DNA Replication

MYC/E2F Targets

G2M Checkpoint

Mitotic Spindle

CDC25A emerged as the top prognostic biomarker

HR = 3.33

p = 0.0246

Biological Interpretation Results suggest resistant tumors exhibit a hyperproliferative transcriptional phenotype driven by dysregulated cell-cycle and replication programs.

Repository Structure data/ scripts/ results/figures/ results/tables/ report.Rmd

Tools & Packages R, TCGAbiolinks, DESeq2, clusterProfiler, enrichplot, pheatmap, survminer, ggplot2

Author Humera