Differentially Expressed Genes in Matched Normal, Cancer, and Lymph Node Metastases Predict Clinical Outcomes in...

Area of Science:

• Genomics and Molecular Biology
• Cancer Research
• Translational Medicine

Background:

• Understanding the molecular drivers of breast cancer (BC) progression and metastasis is crucial for improving patient outcomes.
• Transcriptional profiling offers insights into the genetic landscape of normal tissues, primary tumors, and metastatic sites.

Purpose of the Study:

• To identify transcriptional changes and differentially expressed genes (DEGs) during BC metastatic progression.
• To investigate the prognostic significance of these DEGs in relation to clinical outcomes.
• To analyze gene expression concordance between primary BC and lymph node metastases.

Main Methods:

• Massive parallel RNA sequencing was employed to compare transcriptome profiles of matched normal, cancer, and lymph node metastatic tissues from 7 patients.
• Bioinformatic analyses were conducted to identify DEGs and enriched pathways (KEGG).
• Quantitative real-time PCR and immunohistochemistry validated the expression of selected genes (RAC2, PTGDS).

Main Results:

• High correlation (r=0.962) and patient-specific clustering were observed between gene expression profiles of primary BC and nodal metastases.
• 1522 DEGs were identified between normal and cancer tissues, and 664 DEGs between cancer and nodal metastases.
• The chemokine signaling pathway was significantly enriched in the transition from primary cancer to nodal metastasis.
• Lower expression of RAC2 and PTGDS was significantly associated with worse disease-free survival in BC patients.

Conclusions:

• Gene expression is highly concordant between primary breast cancer and its nodal metastases.
• Specific DEGs, including RAC2 and PTGDS, are associated with BC metastatic progression and clinical prognosis.
• These identified DEGs represent potential novel biomarkers for predicting BC patient prognosis.