Oncotarget

Research Papers:

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 and Wafik S. El-Deiry _

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Oncotarget. 2021; 12:1992-2005. https://doi.org/10.18632/oncotarget.28082

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Abstract

Sofia Leaf1,2,3,4,*, Lindsey Carlsen1,2,3,4,5,* and Wafik S. El-Deiry1,2,3,4,5,6

1 Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA

2 The Joint Program in Cancer Biology, Brown University and the Lifespan Health System, Providence, RI 02903, USA

3 Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA

4 Cancer Center at Brown University, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA

5 Pathobiology Graduate Program, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA

6 Hematology-Oncology Division, Department of Medicine, Rhode Island Hospital and The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA

* These authors contributed equally to this work

Correspondence to:

Wafik S. El-Deiry, email: wafik@brown.edu

Keywords: breast cancer; colorectal cancer; BRCA1; biomarker; early onset

Received: August 31, 2021     Accepted: September 03, 2021     Published: September 28, 2021

Copyright: © 2021 Leaf et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.


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