Impact of BRCA1 mRNA expression on survival of patients breast and colorectal cancer

Oncotarget published "Opposing effects of BRCA1 mRNA expression on patient survival in breast and colorectal cancer and variations among African American, Asian, and younger patients" which reported that LMNB2 is a chromatin remodeling protein that also plays a role in eukaryotic cell proliferation by organizing the nuclear membrane during mitosis.

High expression of LMNB2 in CRC tumors correlates with worse disease-free cumulative and overall survival, and that knocking out the LMNB2 gene allowed for the development of CRC tumors through a mechanism that involved silencing of p21 expression. In line with this, these authors found that young CRC patients, who tend to express high levels of BRCA1 in their tumors, also tend to express low levels of p21 and this may be due to simultaneous high expression of LMNB2.

Breast cancer (BC) is the most common cancer in women besides nonmelanoma skin cancer."

Dr Wafik S. El-Deiry, The Brown University and The Lifespan Health System

12% of women will be diagnosed in their lifetime and the 5-year survival rate is as low as 28% once BC becomes metastatic. There are five molecular subtypes of BC which differ in their molecular presentation: luminal A hormone receptor, luminal B, triple-negative, HER2-enriched, and normal-like, which is similar to luminal A.

Triple-negative breast cancer can be further classified into:

basal-like 1,
basal-like 2,
Immunomodulatory,
Mesenchymal,
mesenchymal-stem like,
luminal androgen receptor, or
Unstable

There is much interest in the field of cancer research regarding development of biomarkers to individualize treatment of existing therapies.

Establishing and validating prognostic biomarkers can allow physicians and patients to make informed decisions that limit exposure of patients to unnecessary treatment and/or ensure that high-risk patients get the treatment they need. Some biomarkers exist for BC and CRC patients. BRCA1 is mutated in less than 1–7% of BC tumors when patients are not selected for family history, but when altered it is a robust biomarker for BC susceptibility with mutation carriers having a lifetime risk of up to 85% for BC.

BRCA1 mutations also predict worse overall survival compared to patients harboring wild-type BRCA1 tumors. BRCA1 mutations in CRC often result in loss of heterozygosity, have been found in almost 50% of sporadic cases, and offer similar utility as a biomarker for worse outcomes although conflicting results have been reported.

The El-Deiry Research Team concluded in their Oncotarget Research Output that surprisingly, there were no genes that correlated with BRCA1 mRNA expression uniquely in BC, but there were several genes that correlated with BRCA1 expression uniquely in CRC. LMNB2 is a chromatin remodeling protein that also plays a role in eukaryotic cell proliferation by organizing the nuclear membrane during mitosis. Despite this, the authors found that high BRCA1 mRNA levels correlate with better outcomes in CRC.

Source:
Journal reference:

Leaf, S., et al. (2021) Opposing effects of BRCA1 mRNA expression on patient survival in breast and colorectal cancer and variations among African American, Asian, and younger patients. Oncotarget. doi.org/10.18632/oncotarget.28082.

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