Identification of Candidate Biomarker and Drug Targets for Improving Endometrial Cancer Racial Disparities

Abstract

Racial disparities in incidence and survival exist for many human cancers. Racial disparities are undoubtedly multifactorial and due in part to differences in socioeconomic factors, access to care, and comorbidities. Within the U.S., fundamental causes of health inequalities, including socio-economic factors, insurance status, access to healthcare and screening and treatment biases, are issues that contribute to cancer disparities. Yet even these epidemiologic differences do not fully account for survival disparities, as for nearly every stage, grade and histologic subtype, survival among Black women is significantly lower than their White counterparts. To address this, we sought to investigate the proteomic profiling molecular features of endometrial cancer in order to detect modifiable and targetable elements of endometrial cancer in different racial groups, which could be essential for treatment planning. The majority of proteins identified to be significantly altered among the racial groups and that can be regulated by existing drugs or investigational agents are enzymes that regulate metabolism and protein synthesis. These drugs have the potential to improve the worse outcomes of endometrial cancer patients based on race.

Endometrial cancer diagnostic and prognostic algorithms based on proteomics, metabolomics, and clinical data: a systematic review

“…From the systematic literature search, 72 research papers were selected based on title and abstract. From these, 19 papers were excluded because focusing on basic cell mechanisms of carcinogenesis with no further investigation on the diagnostic or prognostic potential ( 70 – 80 ), response to metformin ( 81 ), side effect to radiotherapy ( 82 ), racial disparities ( 83 , 84 ), drug resistance ( 85 – 87 ), premenopausal endometrial physiology ( 88 ). Three studies were in silico analyses ( 89 – 91 ).…”

“…A final relevant confounder is the ethnic background, known to affect the proteome profiles ( 83 , 84 ). However, only one study used a cohort from a different geographical background, although still Caucasian to validate their data ( 119 ).…”

Racioethnic Disparities in Endometrial Cancer Outcomes

“…Additionally, unknown molecular and genetic markers may further explain the racioethnic EC mortality disparity. Unfortunately, the TCGA discovery analysis that led to the new molecular classification system did not include a significant number of specimens from black participants with EC [77]. A small number of studies have aimed to profile genomic and proteomic markers associated with EC in black women [74,77].…”

“…Unfortunately, the TCGA discovery analysis that led to the new molecular classification system did not include a significant number of specimens from black participants with EC [77]. A small number of studies have aimed to profile genomic and proteomic markers associated with EC in black women [74,77]. These studies have discovered several biomarkers, but much larger studies are required to validate these findings.…”