Opposing effects of BRCA1 mRNA expression on patient survival in breast and colorectal cancer and variations among African American, Asian, and younger patients

Sofia Leaf,Lindsey Carlsen,Wafik S El-Deiry

doi:10.18632/oncotarget.28082

Abstract

Breast cancer (BC) and colorectal cancer (CRC) are common and show poor survival in advanced stages. Using The Cancer Genome Atlas (TCGA) computational tool cBioPortal, we evaluated overall patient survival in BRCA1 mRNA-low versus -high cohorts (<−1.29 versus >1.05 SD from mean BRCA1 expression, respectively). Analysis included 1082 BC patients with mRNA data (PanCancer Atlas), 382 CRCs (Firehose Legacy) and 592 CRCs (PanCancer Atlas). As previously reported, BRCA1 mRNA-low tumor expression positively correlated with BC patient survival but was negatively associated in CRC. We observed a correlation between BRCA1 mRNA-high and age <45 years at CRC diagnosis using a Fisher’s exact test [Firehose Legacy database (p-value = 0.0091); CRC PanCancer Atlas (p-value = 0.0778)]. We correlated BRCA1 mRNA-low expression and basal BC (p-value = 0.0016) and BRCA1 mRNA-low tumors and frequency of African American patients (p-value = 0.0448) with BC. Other trends included higher frequency of advanced lymph node stage and mucinous adenocarcinoma among BRCA1 mRNA-low CRC and higher frequency of males in BRCA1 mRNA-high BC and CRC. African Americans more frequently had BRCA1 mRNA-low BC and BRCA1 mRNA-high CRC and the opposite was observed among Asians. Using a gene co-expression tool (cBioPortal), we observed TOP2A and ATAD5 levels correlate (Spearman’s correlation>0.6) with BRCA1 in BC and CRC, whereas LMNB2 correlates with BRCA1 in CRC, suggesting tissue-specific BRCA1 interactions. Our results indicate potential for BRCA1 mRNA expression levels as a prognostic biomarker in BC and CRC, suggest tissue-specificity in BRCA1 molecular interactions, and point to BRCA1 mRNA-high levels as a characteristic of CRC tumors in younger versus older individuals.

Highlights

Breast cancer (BC) is the most common cancer in women besides nonmelanoma skin cancer. 12% of women will be diagnosed in their lifetime and the 5-year survival rate is as low as 28% once BC becomes metastatic [1]
It is known that BRCA1 mutations lead to worse outcomes in breast cancer and there is data to suggest that BC patients with low BRCA1 expression may have better overall survival and response to treatment [20, 21]
African Americans more frequently had BRCA1 mRNA-low BC and BRCA1 mRNA high Colorectal cancer (CRC) and the opposite was observed among Asians

Summary

Introduction

Breast cancer (BC) is the most common cancer in women besides nonmelanoma skin cancer. 12% of women will be diagnosed in their lifetime and the 5-year survival rate is as low as 28% once BC becomes metastatic [1]. 12% of women will be diagnosed in their lifetime and the 5-year survival rate is as low as 28% once BC becomes metastatic [1]. There are five molecular subtypes of BC which differ in their molecular presentation: luminal A (hormone receptor (HR)+, HER2–), luminal B (HR+, HER2–/+), triplenegative (HR–, HER2–), HER2-enriched (HR–, HER2+), and normal-like, which is similar to luminal A. Colorectal cancer (CRC) is the third leading cause of cancer deaths and like BC, is especially deadly when it metastasizes (5-year survival rate at this point is ~13%). Some hypotheses have been presented such as cancer-promoting changes in the microbiome due to unhealthy diet and sedentary lifestyle or obesity, but little has been done as far as investigating the molecular basis of this or any other mechanism [4]

Methods

Results

Conclusion