RESUMEN

The Tripartite motif-containing 28 (TRIM28) transcriptional cofactor is significantly upregulated in high-grade and metastatic prostate cancers. To study the role of TRIM28 in prostate cancer progression in vivo, we generated a genetically-engineered mouse model, combining prostate-specific inactivation of Trp53, Pten and Trim28. Trim28 inactivated NPp53T mice developed an inflammatory response and necrosis in prostate lumens. By conducting single-cell RNA sequencing, we found that NPp53T prostates had fewer luminal cells resembling proximal luminal lineage cells, which are cells with progenitor activity enriched in proximal prostates and prostate invagination tips in wild-type mice with analogous populations in human prostates. However, despite increased apoptosis and reduction of cells expressing proximal luminal cell markers, we found that NPp53T mouse prostates evolved and progressed to invasive prostate carcinoma with a shortened overall survival. Altogether, our findings suggest that TRIM28 promotes expression of proximal luminal cell markers in prostate tumor cells and provides insights into TRIM28 function in prostate tumor plasticity.

Asunto(s)

Plasticidad de la Célula , Neoplasias de la Próstata , Humanos , Masculino , Ratones , Animales , Neoplasias de la Próstata/patología , Proteína 28 que Contiene Motivos Tripartito/genética , Proteína 28 que Contiene Motivos Tripartito/metabolismo , Próstata/patología , Modelos Animales de Enfermedad , Células Madre Neoplásicas/patología

RESUMEN

OBJECTIVE: To measure the association of race, ethnicity, comorbidities, and insurance status with need for hospitalization of symptomatic emergency department patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: This study is a cohort study of symptomatic patients presenting to a single emergency department (ED) with laboratory-confirmed SARS-CoV-2 infection from March 7-August 9, 2020. We collected patient-level information regarding demographics, insurance status, comorbidities, level of care, and mortality using a structured chart review. We compared characteristics of patients categorized by (1) home discharge, (2) general hospital ward admission, and (3) intensive care unit (ICU) admission or death within 30 days of the index visit. Univariate and multivariable logistic regression analyses were performed to report odds ratios (OR) and 95% confidence intervals (95% CI) between hospital admission versus ED discharge home and between ICU care versus general hospital ward admission. RESULTS: In total, 994 patients who presented to the ED with symptoms were included in the analysis with 551 (55.4%) patients discharged home, 314 (31.6%) patients admitted to the general hospital ward, and 129 (13.0%) admitted to the ICU or dying. Patients requiring admission were more likely to be Black or to have public insurance (Medicaid and/or Medicare). Patients who were admitted to the ICU or dying were more likely aged ≥ 65 years or male. In multivariable logistic regression, old age, public insurance, diabetes, hypertension, obesity, heart failure, and hyperlipidemia were independent predictors of hospital admission. When comparing those who needed ICU care versus general hospital ward admission in univariate logistic regression, patients with Medicaid (OR 2.4, 95% CI 1.2-4.6), Medicare (OR 4.2, 95% CI 2.1-8.4), Medicaid and Medicare (OR 4.3, 95% CI 2.4-7.7), history of chronic obstructive pulmonary disease (OR 2.2, 95% CI 1.2-4.2), hypertension (OR 1.7, 95% CI 1.1-2.7), and heart failure (OR 2.6, 95% CI 1.4-4.7) were more likely to be admitted into the ICU or die; Black (OR 1.1, 95% CI 0.4-2.9) and Hispanic/Latino (OR 1.0, 95% CI 0.6-1.8) patients were less likely to be admitted into the ICU; however, the associations were not statistically significant. In multivariable logistic regression, old age, male sex, public insurance, and heart failure were independent predictors of ICU care/death. CONCLUSION: Comorbidities and public insurance are predictors of more severe illness for patients with SARS-CoV-2. This study suggests that the disparities in severity seen in COVID-19 among Black patients may be attributable, in part, to low socioeconomic status and chronic health conditions.

RESUMEN

OBJECTIVE: To measure the association of race, ethnicity, comorbidities, and insurance status with need for hospitalization of symptomatic Emergency Department (ED) patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: This study is a retrospective case-series of symptomatic patients presenting to a single ED with laboratory-confirmed SARS-CoV-2 infection from March 12-August 9, 2020. We collected patient-level information regarding demographics, public insurance status (Medicare or Medicaid), comorbidities, level of care, and mortality using a structured chart review. We compared demographics and comorbidities of patients who were (1) able to convalesce at home, (2) required admission to general medical service, (3) required admission to intensive care unit (ICU), or (4) died within 30 days of the index visit. Multivariable logistic regression analyses were performed to report adjusted odds ratios (aOR) and the associated 95% confidence intervals (95% CI) with hospital admission versus ED discharge home. RESULTS: In total, 993 patients who presented to the ED with symptoms were included in the analysis with 370 (37.3%) patients requiring hospital admission and 70 (7.1%) patients requiring ICU care. Patients requiring admission were more likely to be Black or African American, to be Hispanic or Latino, or to have public insurance (either Medicaid or Medicare.) On multivariable logistic regression analysis comparing which patients required hospital admission, African-American race (aOR 1.4, 95% CI 0.7-2.8) and Hispanic ethnicity (aOR 1.1, 95% CI 0.5-2.0) were not associated with need for admission but, public insurance (Medicaid: aOR 3.4, 95% CI 2.2-5.4; Medicare: aOR 2.6, 95% CI 1.2-5.3; Medicaid and Medicare: aOR 3.6 95% CI 2.1-6.2) and the presence of hypertension (aOR 1.8, 95% CI 1.2-2.7), diabetes (aOR 1.6, 95% CI 1.1-2.5), obesity (aOR 1.7, 95% CI 1.1-2.5), heart failure (aOR 3.9, 95% CI 1.4-11.2), and hyperlipidemia (aOR 1.8, 95% CI 1.2-2.9) were identified as independent predictors of hospital admission. CONCLUSION: Comorbidities and public insurance are predictors of more severe illness for patients with SARS-CoV-2. This study suggests that the disparities in severity seen in COVID-19 among African Americans and Hispanics are likely to be closely related to low socioeconomic status and chronic health conditions and do not reflect an independent predisposition to disease severity.