Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by...

Area of Science:

• Biochemistry
• Oncology
• Proteomics

Background:

• Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease with unpredictable progression to invasive breast cancer (IBC).
• Extracellular matrix (ECM) alterations are increasingly recognized in breast cancer progression.
• The spatial regulation of the ECM proteome in DCIS and its relation to IBC remains understudied.

Purpose of the Study:

• To investigate and compare the spatial ECM proteomes of DCIS and IBC.
• To identify ECM proteomic signatures that can discriminate between DCIS and IBC.
• To explore the influence of proximity to invasive cancer on the DCIS microenvironment.

Main Methods:

• Multiplexed spatial proteomics was employed on tissue sections from 22 patients with pure DCIS, mixed DCIS-IBC, or pure IBC.
• Detailed pathological annotations were used to define regions of interest and surrounding microenvironments.
• Quantitative analysis of 1,005 ECM peptides was performed across different pathological contexts.

Main Results:

• A total of 43 significantly altered ECM peptides were identified when comparing DCIS and IBC pathologies.
• Eight specific fibrillar collagen peptides demonstrated high specificity and sensitivity in distinguishing between DCIS and IBC.
• Spatial proteomic imaging revealed heterogeneity within DCIS lesions and an 'invasive cancer field effect' where proximity to IBC altered the DCIS ECM profile.

Conclusions:

• The ECM proteome differs significantly between DCIS and IBC, with specific collagen peptides serving as potential biomarkers.
• Spatial proteomic analysis provides novel molecular insights into the tumor microenvironment of DCIS and its relationship with IBC.
• Understanding the ECM proteomic microenvironment is crucial for deciphering the progression from DCIS to IBC.