Admin-Core-001

管理核心-001

• 批准号: 10707753
• 负责人: UPENDER MANNE
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707753
• 关键词: Admin; Core; 001

PNETs are cancers that arise from hormone-producing cells of the pancreas. They are usually diagnosed in late stages, with few treatments available. PNETs are the second most common pancreatic cancer and are rapidly increasing in incidence. Black pNET patients have worse survival and higher rates of cancer spread associated with smaller tumors than White patients. These clinical disparities suggest a biologic difference between these two patient groups. Guidelines for treating pNETs are mostly based on data from White patients and may not apply to Black patients. Differences in cancer biology between racial groups that affect disease severity has been discovered in other cancers. Notably, there are differences in epigenetic modifications between different ethnic and racial groups. Epigenetic regulation of gene expression, including DNA methylation (whereby chemical groups are added to DNA to alter the generation of gene product), is an important mechanism by which environmental factors, lifestyle, and stress can affect an individual’s genes. pNETs are known to have high rates of epigenetic dysregulation. However, nothing is known about the differences in the (epi)genetics of pNETs between Black and White patients, as Black patients represent under 1% of patients included in genetic studies of pNETs. Other key differences may exist between how tumor from different patient populations interact with the normal tissue environment or the patient’s immune system. The goal of this project is to investigate the causes of the clinical outcomes differences between Black and White patients with pNETs. These differences may be at the (epi)genetic level, how the tumor interacts with surrounding cells, or environmentally influenced. The proposed research will compare the genomes and gene regulation systems between the two patient groups to find what is driving the clinical differences seen at a cellular level. This will demonstrate if the clinical outcome differences could be due to how the body keeps the tumor at bay and determine what key stressors exist today in the Black pNET patient population in the Deep South. While this study is aimed at understanding the ways in which epigenetic and gene expression changes affect pNETs in Black patients, the findings will profoundly impact the direction of both pNET treatment and research for the entire patient population.

PNETs是一种由胰腺分泌激素的细胞引起的癌症。它们通常在晚期被诊断出来，几乎没有可用的治疗方法。PNETs是第二种最常见的胰腺癌，发病率正在迅速上升。与白人患者相比，黑人pnet患者的存活率更低，与较小的肿瘤相关的癌症转移率更高。这些临床差异表明这两个患者组之间存在生物学差异。PNETs的治疗指南大多基于白人患者的数据，可能不适用于黑人患者。在其他癌症中也发现了影响疾病严重程度的种族群体之间的癌症生物学差异。值得注意的是，不同民族和种族群体之间的表观遗传修饰存在差异。基因表达的表观遗传调控，包括DNA甲基化(在DNA中添加化学基团以改变基因产物的生成)，是环境因素、生活方式和压力影响个人基因的重要机制。众所周知，PNETs具有很高的表观遗传失调比率。然而，黑人和白人患者之间的PNETs(Epi)遗传学差异尚不清楚，因为黑人患者在PNETs遗传学研究中所占患者的比例不到1%。来自不同患者群体的肿瘤与正常组织环境或患者免疫系统的相互作用方式可能存在其他关键差异。本项目的目标是调查黑人和白人PNETs患者临床结果差异的原因。这些差异可能是在(表观)遗传水平上，肿瘤如何与周围细胞相互作用，或环境影响。这项拟议的研究将比较两组患者的基因组和基因调控系统，以找出在细胞水平上导致临床差异的原因。这将证明临床结果的差异是否可能是由于身体如何控制肿瘤，并确定目前在南方腹地的黑人pnet患者群体中存在哪些关键应激源。虽然这项研究的目的是了解表观遗传学和基因表达变化如何影响黑人患者的PNETs，但这一发现将深刻影响整个患者群体的pNET治疗和研究的方向。