Race influences survival in glioblastoma patients with KPS ≥ 80 and associates with genetic markers of retinoic acid metabolism

Wu, Meijing; Miska, Jason; Xiao, Ting; Zhang, Peng; Kane, Jason M.; Balyasnikova, Irina V.; Chandler, James P.; Horbinski, Craig; Lesniak, Maciej S.

doi:10.1007/s11060-019-03110-5

Cited by 20 publications

(12 citation statements)

References 37 publications

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“…First, our data highlight that expression of the pseudogene, CRYβB2P1, is associated with Black/African-American breast cancer patients compared to White and Asian patient samples, and CRYβB2P1 expression levels are higher compared to CRYβB2 in all TCGA breast cancer samples. Other studies have highlighted CRYβB2 as a health disparity gene in breast cancer, but our data suggest technical difficulties in distinguishing between the expression levels of the two genes and that the more likely disparity target is CRYβB2P1 [7, 11, 12, 14–17]. Second, our data suggest CRYβB2P1 functions as a ncRNA in triple-negative breast cancers to alter transcription.…”

Section: Discussionmentioning

confidence: 56%

“…Crystallin β B2 (CRYβB2) has recently drawn particular interest because of its genetic association with overall survival and African-American ethnicity in multiple cancers, including breast, colorectal, renal cell carcinoma, glioblastoma, and prostate tumors [7, 11, 12, 14–17]. In a small prediction analysis study, 91% of all African-American/Black patients ( n = 33) and 94% of all White patients ( n = 36) were correctly classified according to race using CRYβB2 as one of the two-gene signatures in prostate tumors, PSPHL being the other gene classifier [12].…”

Section: Introductionmentioning

confidence: 99%

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A functional role for the cancer disparity-linked genes, CRYβB2 and CRYβB2P1, in the promotion of breast cancer

et al. 2019

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Background In the USA, the breast cancer mortality rate is 41% higher for African-American women than non-Hispanic White women. While numerous gene expression studies have classified biological features that vary by race and may contribute to poorer outcomes, few studies have experimentally tested these associations. CRYβB2 gene expression has drawn particular interest because of its association with overall survival and African-American ethnicity in multiple cancers. Several reports indicate that overexpression of the CRYβB2 pseudogene, CRYβB2P1, and not CRYβB2 is linked with race and poor outcome. It remains unclear whether either or both genes are linked to breast cancer outcomes. This study investigates CRYβB2 and CRYβB2P1 expression in human breast cancers and breast cancer cell line models, with the goal of elucidating the mechanistic contribution of CRYβB2 and CRYβB2P1 to racial disparities. Methods Custom scripts for CRYβB2 or CRYβB2P1 were generated and used to identify reads that uniquely aligned to either gene. Gene expression according to race and tumor subtype were assessed using all available TCGA breast cancer RNA sequencing alignment samples (n = 1221). In addition, triple-negative breast cancer models engineered to have each gene overexpressed or knocked out were developed and evaluated by in vitro, biochemical, and in vivo assays to identify biological functions. Results We provide evidence that CRYβB2P1 is expressed at higher levels in breast tumors compared to CRYβB2, but only CRYβB2P1 is significantly increased in African-American tumors relative to White American tumors. We show that independent of CRYβB2, CRYβB2P1 enhances tumorigenesis in vivo via promoting cell proliferation. Our data also reveal that CRYβB2P1 may function as a non-coding RNA to regulate CRYβB2 expression. A key observation is that the combined overexpression of both genes was found to suppress cell growth. CRYβB2 overexpression in triple-negative breast cancers increases invasive cellular behaviors, tumor growth, IL6 production, immune cell chemoattraction, and the expression of metastasis-associated genes. These data underscore that both CRYβB2 and CRYβB2P1 promote tumor growth, but their mechanisms for tumor promotion are likely distinct. Conclusions Our findings provide novel data emphasizing the need to distinguish and study the biological effects of both CRYβB2 and CRYβB2P1 as both genes independently promote tumor progression. Our data demonstrate novel molecular mechanisms of two understudied, disparity-linked molecules.

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Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

A functional role for the cancer disparity-linked genes, CRYβB2 and CRYβB2P1, in the promotion of breast cancer

et al. 2019

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“…Human genetics contribute to the propensity and severity of diseases 21,[30][31][32][33][34][35][36][37] . Sometimes the contribution is straightforward; a single allele variation found in Ashkenazi Jews, causes the vast majority of Tay-Sachs disease 36 .…”

Section: Discussionmentioning

confidence: 99%

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Singh¹,

Hernandez²,

Aronow³

et al. 2020

Preprint

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The COVID-19 pandemic has affected African American populations disproportionately with respect to prevalence, morbidity, and mortality. Because gene expression profiles represent combined genetic, socioenvironmental, and physiological effects, and could provide therapeutic biomarkers and environmental mitigation strategies, we undertook a large-scale assessment of differential gene expression between African Americans and European Americans. To do this, we mined RNA-Seq datasets from normal and diseased (tumor) conditions whose metadata could be used to evaluate differential patterns. We observed widespread differential expression of genes implicated in COVID-19 and integral to epithelial boundary function, inflammation, infection, and reactive oxygen stress. Notably, expression of the little-studied F8A2 gene is up to 40-fold greater in African Americans. F8A2, like F8A1, encodes HAP40 protein, which mediates early endosome movement. African American gene expression signatures reveal increased number or activity of esophageal glandular cells and lung ACE2-positive basal keratinocytes. These findings have potential to establish prognostic signatures, refine approaches to minimizing risk of severe infection, and improve precision treatment of COVID-19.

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“…Genetics of human populations contribute to the propensity and severity of diseases 37,39,41,41,45,[93][94][95][96][97][98] . Sometimes the contribution is straightforward; a single allele variation found in Ashkenazi Jews, causes the vast majority of Tay-Sachs disease 99 .…”

Section: Discussionmentioning

confidence: 99%

Differential expression of COVID-19-related genes in European Americans and African Americans

Singh

Wurtele

2020

Preprint

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The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington’s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.

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Race influences survival in glioblastoma patients with KPS ≥ 80 and associates with genetic markers of retinoic acid metabolism

Cited by 20 publications

References 37 publications

A functional role for the cancer disparity-linked genes, CRYβB2 and CRYβB2P1, in the promotion of breast cancer

A functional role for the cancer disparity-linked genes, CRYβB2 and CRYβB2P1, in the promotion of breast cancer

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Differential expression of COVID-19-related genes in European Americans and African Americans

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