Looking at molecular changes for clues to differences in breast cancer prognosis

MUSC Hollings Cancer Center researcher Dr.

Angel is an analytical chemist by training, and she is interested in what is going on at the molecular level

N-glycosylation is a metabolic process that produces sugar modifications on protein structures

"We were trying to look at differences in social status between black women and white women and compare that to molecular factors that could be predictive,

She notes that it's important to start looking at differences in breast tissue before cancer develops

"Differences in baseline glycosylation in normal breast tissue may contribute to specific differences in breast tissue biology that disproportionately affect black women

Angel's team obtained normal breast tissue samples donated by black and white women from the Susan G.

The samples included tissue from 30 white and 30 black women, and the results suggest that metabolic patterns related to socioeconomic stress are a potential contributor to differences in breast cancer between black and white women

The study may also be the first to look at the spatial distribution of focal structures in normal breast tissue, Angel said

The study states that, based on the current literature and the research team's findings, in normal tissues, altered focal patterns may contribute to a tumor-tolerant microenvironment that is associated with more severe breast cancers influenced by genetic ancestry and BMI (body mass index).

Angel said they found that in the ancestral-defined normal breast, a post-translational modification called glycosylation (sugar residues added to proteins) varied by BMI

BMI and weight gain are already considered significant risk factors for breast cancer, Angel said, citing a study that found that an 11-pound BMI increase was associated with a 2 percent higher risk of breast cancer

Continue to study the spatial distribution and post-translational modifications of collagen types to gain a more complete understanding of the impact of socioeconomic status on specific biological factors, processes, and modifications that are critical in promoting the development of diseases such as breast cancer, Angel said

BMI is only part of it

This may imply that the immune responses triggered by specific lifestyle stressors are different in white and black women, and future research should look at glycosylation changes associated with immune components, a mechanism linking molecular markers to socioeconomic stressors emerging areas of promising research

"This expands our understanding of the regulation of glycosylation, and the possibility that this regulation may be influenced by socioeconomic stressors

Angel said the research is at an important juncture, as she has developed a method that allows her team to determine the spatial structure of collagen in the tissue microenvironment
.
This allowed them to study not only where the collagen structure was post-translationally modified, but also the location, cell type and expression associated with this change
.

The researchers' goal is to use molecular signatures to make a more specific diagnosis of breast cancer, possibly including subtypes of breast cancer
.
In addition, defining collagen structures more specifically may help them identify biomarkers and develop more targeted treatments
.

"The disparity in breast cancer mortality in black women is an urgent problem that needs to be addressed," she said
.
"My hope is that we can discover the molecular signatures that shape tumors permitting breast density and develop treatments that can reverse this change
.
"

Journal Reference:

1. Denys Rujchanarong, Danielle Scott, Yeonhee Park, Sean Brown, Anand S.
   Mehta, Richard Drake, George E.
   Sandusky, Harikrishna Nakshatri, Peggi M.
   Angel.
   Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer .
   Frontiers in Oncology, 2022; 12 DOI: 10.
   3389/fonc.
   2022.
   876651