African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks
Abstract Background Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3423-1 |
| _version_ | 1811221900915900416 |
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| author | Hayriye Verda Erkizan Kory Johnson Svetlana Ghimbovschi Deepa Karkera Gregory Trachiotis Houtan Adib Eric P. Hoffman Robert G. Wadleigh |
| author_facet | Hayriye Verda Erkizan Kory Johnson Svetlana Ghimbovschi Deepa Karkera Gregory Trachiotis Houtan Adib Eric P. Hoffman Robert G. Wadleigh |
| author_sort | Hayriye Verda Erkizan |
| collection | DOAJ |
| description | Abstract Background Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. Methods To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. Results We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. Conclusion Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC. |
| first_indexed | 2024-04-12T08:07:51Z |
| format | Article |
| id | doaj.art-7ab688e390594178ab1dd5d0310cf450 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T08:07:51Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7ab688e390594178ab1dd5d0310cf4502022-12-22T03:41:06ZengBMCBMC Cancer1471-24072017-06-0117111310.1186/s12885-017-3423-1African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networksHayriye Verda Erkizan0Kory Johnson1Svetlana Ghimbovschi2Deepa Karkera3Gregory Trachiotis4Houtan Adib5Eric P. Hoffman6Robert G. Wadleigh7Institute for Clinical Research, Department of Veteran Affairs Medical Center (VAMC)Bioinformatics Neuroscience Group, Information Technology Program, National Institute of Neurological Disorders & StrokeResearch Center for Genetic Medicine, Children’s National Medical CenterInstitute for Clinical Research, Department of Veteran Affairs Medical Center (VAMC)Cardiothoracic Surgery, VAMCRadiology Service, VAMCResearch Center for Genetic Medicine, Children’s National Medical CenterInstitute for Clinical Research, Department of Veteran Affairs Medical Center (VAMC)Abstract Background Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. Methods To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. Results We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. Conclusion Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.http://link.springer.com/article/10.1186/s12885-017-3423-1mRNA expressionMicroarrayDown-regulated genesUp-regulated genesPathway analysisTargeted therapy |
| spellingShingle | Hayriye Verda Erkizan Kory Johnson Svetlana Ghimbovschi Deepa Karkera Gregory Trachiotis Houtan Adib Eric P. Hoffman Robert G. Wadleigh African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks BMC Cancer mRNA expression Microarray Down-regulated genes Up-regulated genes Pathway analysis Targeted therapy |
| title | African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks |
| title_full | African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks |
| title_fullStr | African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks |
| title_full_unstemmed | African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks |
| title_short | African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks |
| title_sort | african american esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks |
| topic | mRNA expression Microarray Down-regulated genes Up-regulated genes Pathway analysis Targeted therapy |
| url | http://link.springer.com/article/10.1186/s12885-017-3423-1 |
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