Spatial Transcriptomics and Bulk RNA-Seq Analysis Revealed Molecular Classification of Invasive Lobular Carcinoma

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Invasive lobular carcinoma (ILC) is a distinct breast cancer subtype with variable histological features and prognoses.
• Pleomorphic-ILC (P-ILC) is associated with a worse prognosis compared to classic-ILC (C-ILC) due to high-grade nuclear atypia.
• The molecular underpinnings differentiating P-ILC from C-ILC are not well understood.

Purpose of the Study:

• To investigate the molecular differences between C-ILC and P-ILC.
• To identify molecular subtypes of ILC and their prognostic implications.
• To explore potential diagnostic markers and therapeutic targets for ILC.

Main Methods:

• Spatial transcriptomic profiling was performed on fresh-frozen C-ILC and P-ILC samples.
• Bulk RNA-sequencing datasets were used to confirm reproducibility.
• Molecular clustering analysis was conducted on differentially expressed genes.

Main Results:

• P-ILC showed significant enrichment of cellular response to heat stress.
• Three molecular subtypes of ILC were identified: proliferative (PR), immunoreactive (IM), and stroma-rich (ST).
• PR subtypes were associated with P-ILC, while ST subtypes were associated with C-ILC, and these subtypes correlated with distinct prognostic outcomes.

Conclusions:

• Molecular profiling may offer a more accurate prognostic assessment for ILC than traditional histological classification.
• The identified molecular subtypes and pathways (e.g., heat stress response) may serve as potential diagnostic markers and therapeutic targets for ILC.
• Current treatment strategies for ILC do not sufficiently consider molecular subtype classification.