Identification of Poor Prognostic Markers in Triple-Negative Breast Cancer Using Whole Exome Sequencing.

Area of Science:

• Oncology
• Genomics
• Cancer Research

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited prognostic markers.
• Programmed death ligand 1 (PD-L1) is a biomarker, but its utility is restricted, especially in PD-L1-negative cases.
• Identifying new molecular markers is crucial for better prognostication and treatment in TNBC.

Purpose of the Study:

• To investigate distinct mutational landscapes in TNBC based on PD-L1 expression.
• To identify novel prognostic variants associated with survival outcomes in TNBC.
• To explore the role of genomic profiling in refining TNBC prognostic stratification.

Main Methods:

• Whole-exome sequencing of 38 TNBC tumor tissues.
• Immunohistochemistry to assess PD-L1 expression (positive/negative).
• Analysis of somatic variants and mutational signatures; survival analyses.

Main Results:

• TNBC tumors showed distinct mutational signatures based on PD-L1 status (SBS5 for PD-L1-negative, SBS6 for PD-L1-positive).
• Twelve PD-L1-negative-specific and seven PD-L1-positive-specific variants were identified.
• Mutations in ANGPTL5 and KIAA1549L were linked to worse overall survival in PD-L1-negative TNBC.

Conclusions:

• PD-L1 status defines distinct mutational profiles and prognostic variants in TNBC.
• ANGPTL5 and KIAA1549L variants show potential as prognostic markers for PD-L1-negative TNBC.
• Genomic data integration can enhance prognostic accuracy for TNBC patients.