Higher expression of SATB2 in hepatocellular carcinoma of African Americans determines more aggressive phenotypes than those of Caucasian Americans

Yu, Wei; Roy, Sitikantha; LaVeist, Thomas A.; Shankar, Sharmila; Srivastava, Rajendra

doi:10.1111/jcmm.14652

Cited by 14 publications

(40 citation statements)

References 56 publications

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“…These studies suggest that a consequence of differential dysregulation of HNF4α transcriptional activity may lead to racial disparities in HCC, and the development of HNF4α inhibitors may be useful to eliminate HCC racial disparities. We have recently demonstrated that HCC cells derived from AA expressed a higher level of SATB2 than those from CAs, and the expression of SATB2 was negatively correlated with tumor suppressive miR34a . The data suggested that the higher expression of SATB2 may be responsible for the disparity in HCC outcomes.…”

Section: Genesmentioning

confidence: 95%

Assessment of risk factors, and racial and ethnic differences in hepatocellular carcinoma

et al. 2020

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Despite improved screening and surveillance guidelines, significant race/ethnicity‐specific disparities in hepatocellular carcinoma (HCC) continue to exist and disproportionately affect minority and disadvantaged populations. This trend indicates that social determinants, genetic, and environmental factors are driving the epidemic at the population level. Race and geography had independent associations with risk of mortality among patients with HCC. The present review discusses the risk factors and issues related to disparities in HCC. The underlying etiologies for these disparities are complex and multifactorial. Some of the risk factors for developing HCC include hepatitis B (HBV) and hepatitis C (HCV) viral infection, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, smoking and alcohol consumption. In addition, population genetics; socioeconomic and health care access; treatment and prevention differences; and genetic, behavioral, and biological influences can contribute to HCC. Acculturation of ethnic minorities, insurance status, and access to health care may further contribute to the observed disparities in HCC. By increasing awareness, better modalities for screening and surveillance, improving access to health care, and adapting targeted preventive and therapeutic interventions, disparities in HCC outcomes can be reduced or eliminated.

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Section: Genesmentioning

confidence: 95%

Assessment of risk factors, and racial and ethnic differences in hepatocellular carcinoma

et al. 2020

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“…[17][18][19] We and others have demonstrated that human normal epithelial cells of several organs do not express SATB2 gene; however, it is highly expressed in cancer cell lines, CSCs and primary tumours of colon, liver, breast and pancreas. 7-9, [20][21][22] Our recent work showed that overexpression of was demonstrated by several groups, suggesting its role was oncogenic. 20,22,25,26 In contrary to above findings, inhibition of SATB2 expression resulted in enhanced cell growth, metastasis and poor prognosis in colorectal cancer 27,28 and overexpression of SATB2 reduced colorectal cancer cell proliferation, invasion and migration.…”

Section: Satb2 Reg Ul Ate S Mali G Nant Tr Ans Formationmentioning

confidence: 99%

“…7-9, [20][21][22] Our recent work showed that overexpression of was demonstrated by several groups, suggesting its role was oncogenic. 20,22,25,26 In contrary to above findings, inhibition of SATB2 expression resulted in enhanced cell growth, metastasis and poor prognosis in colorectal cancer 27,28 and overexpression of SATB2 reduced colorectal cancer cell proliferation, invasion and migration. 29 The reasons for this discrepancy of SATB2 function in colorectal cancer is not clear, but it could be related to the differentiation stage of the cells as gene expression profile changes in different regions of the colorectal tissues (ie proximal vs distal, and left vs right).…”

Section: Satb2 Reg Ul Ate S Mali G Nant Tr Ans Formationmentioning

confidence: 99%

“…[7][8][9]11,24 In contrast, SATB2 inhibition by shRNA reverses EMT characteristics. 7-9, 22 The lncRNA, SATB2-AS1 (the antisense transcript of SATB2) inhibits cancer cell growth, EMT, and metastasis, and regulates immune response in colorectal cancer. 31,32 These studies clearly demonstrate the role of SATB2 in EMT and metastasis.…”

Section: Satb2 Reg Ul Ate S Epithelial-me S En Chymal Tr Ans Itionmentioning

confidence: 99%

“…26 In CSCs derived from human HCC, the expression of SATB2 was negatively correlated with miR34a and SATB2 rescued the miR-34a-mediated inhibition of CSC's viability. 22 Other miRNAs such as miR-31, miR-34, miR-182 and miR-599 can regulate SATB2 in solid tumours mainly in breast, liver, lung and colorectal cancer. miR-140-5p inhibited osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting SATB2, and in the same study, authors have shown that long noncoding RNA H19 promoted osteogenic differentiation of BM-MSCs through regulation of miR-140-5p/SATB2 axis.…”

Section: Satb2 Reg Ul Ate S Epithelial-me S En Chymal Tr Ans Itionmentioning

confidence: 99%

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SATB2 is a novel biomarker and therapeutic target for cancer

Roy

Shrivastava

Srivastav

et al. 2020

J Cellular Molecular Medi

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Gene expression is tightly controlled by epigenetic regulators and transcription factors. One such factor is SATB2 (special AT-rich binding protein-2) which influences gene expression by regulating chromatin architecture and by acting as a transcriptional co-factor. 1-5 This gene is conserved in humans and mouse. In humans, there are three transcripts which encodes for SATB2 protein. Genetic engineering techniques have demonstrated that SATB2 knockout mice are defective in bone development and osteoblast differentiation. 2 Furthermore, the expression of SATB2 has been associated with craniofacial patterning and osteoblast differentiation, 2 as well as development of cortical neurons. 3-6

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Black Patients With Cirrhosis Have Higher Mortality and Lower Transplant Rates: Results From a Metropolitan Cohort Study

et al. 2021

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BaCKgRoUND aND aIMS: Estimates of racial disparity in cirrhosis have been limited by lack of large-scale, longitudinal data, which track patients from diagnosis to death and/ or transplant. appRoaCH aND ReSUltS: We analyzed a large, metropolitan, population-based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End-Stage Liver Disease-Sodium (MELD-Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD-Na, and proportion of alcohol-associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (P < 0.001 for all). In multivariate competing risk analysis, Black patients had a 26% increased hazard of liver-related death (subdistribution HR, 1.26; 95% CI, [1.15-1.38]; P < 0.001).CoNClUSIoNS: Black patients with cirrhosis have discordant outcomes. Further research is needed to determine how to address these real disparities in the field of hepatology. (Hepatology 2021;74:926-936). R acial disparities for Black patients have been described in many conditions, including liver disease. (1,2) Identification and correction of disparities are essential in this field given that cirrhosis is estimated to affect many millions people every year and is a leading cause of death. (3,4) Despite the importance of this topic, the relationship between Black race and outcomes in patients with cirrhosis has not been well examined. In the pre-MELD (Model for End-Stage Liver Disease) area, one study from 1998 to 2003 demonstrated that hospitalized Black patients were more likely to have delayed treatment for variceal bleeding and presented with a higher incidence of HE compared to White patients. (5) Another study, using the Surveillance, Epidemiology, and End Results cancer database, suggested that Black patients with HCC were less likely to be recommended for curative resection and have worse HCC survival compared to White patients. (6) Unfortunately, these studies capture a small segment of the population of patients with cirrhosis >20 years ago and therefore are unlikely to represent the current state of disparity.

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Higher expression of SATB2 in hepatocellular carcinoma of African Americans determines more aggressive phenotypes than those of Caucasian Americans

Cited by 14 publications

References 56 publications

Assessment of risk factors, and racial and ethnic differences in hepatocellular carcinoma

Assessment of risk factors, and racial and ethnic differences in hepatocellular carcinoma

SATB2 is a novel biomarker and therapeutic target for cancer

Black Patients With Cirrhosis Have Higher Mortality and Lower Transplant Rates: Results From a Metropolitan Cohort Study

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