Abstract
PurposeTo assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival. MethodsPreoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355). ResultsCPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS. ConclusionCPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.
Highlights
To assess whether contralateral parenchymal enhancement (CPE) on magnetic resonance imaging (MRI) is associated with gene expression pathways in ERþ/human epidermal growth factor 2negative (HER2-)breast cancer, and if so, whether such pathways are related to survival
We hypothesize that CPE could represent the diseased breast before tumorigenesis [4], in which case CPE could be associated with an environment that gives rise to a certain type of tumor, or that CPE is secondarily affected by tumor-induced systemic effects
Analysis of individual genes in the KEGG_PROTEASOME pathway showed that the proteasome subunit beta 10 (PSMB10) gene had the strongest correlation with CPE: 0.389
Summary
To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ERþ/HER2-breast cancer, and if so, whether such pathways are related to survival. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N 1⁄4 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis The latter was done for the METABRIC cohort (N 1⁄4 1355). Enhancement of contralateral parenchymal tissue was associated with the presence of breast cancer (in the contralateral breast) [21], and ipsilateral parenchymal enhancement was associated with various biological pathways expressed in the tumor [19,22] Based on these findings, we hypothesize that CPE could represent the diseased breast before tumorigenesis [4], in which case CPE could be associated with an environment that gives rise to a certain type of tumor, or that CPE is secondarily affected by tumor-induced systemic effects. The purpose of this study was to investigate whether CPE is associated with biological pathways in the tumor, and, if so, whether these CPE-associated biological pathways expressed in the tumor carry prognostic information
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