Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• A ternary complex involving PGRMC1, σ2R/TMEM97, and LDLR plays a role in cholesterol transport.
• The prognostic significance of individual components of this complex in breast cancer remains to be fully elucidated.

Purpose of the Study:

• To investigate PGRMC1, σ2R/TMEM97, and LDLR as prognostic breast cancer biomarkers.
• To define their expression patterns in established molecular subtypes of breast cancer.
• To assess their association with cellular proliferation and recurrence-free survival.

Main Methods:

• Analysis of 4,463 invasive breast cancers using gene expression signature-based assays for proliferation.
• Cox proportional hazards regression and multivariate Cox analysis for relapse-free survival.
• Stratification of PGRMC1–σ2R/TMEM97–LDLR expression by immunohistochemistry, molecular subtype, tumor grade, and size.

Main Results:

• TMEM97 showed the strongest correlation with cellular proliferation, especially in estrogen receptor (ER)-positive disease (r = 0.59).
• TMEM97 and PGRMC1 expression were associated with an increased risk of early recurrence, particularly in ER+/HER2− disease (HR = 1.5) and ER+ malignancies (HR = 1.49).
• No increased recurrence risk was observed in ER−/HER2− or ER− disease based on TMEM97 expression.

Conclusions:

• Components of the PGRMC1–σ2R/TMEM97–LDLR complex are biomarkers associated with cellular proliferation and early breast cancer recurrence.
• These findings can guide further research into their role in aggressive disease and potential therapeutic targets.
• Understanding the interplay of proliferation and cholesterol metabolism in breast cancer is crucial for malignant transformation and propagation.