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.

胰腺癌是由胰腺的分泌细胞引起的癌症。它们通常在晚期被诊断出来，几乎没有治疗方法。胰腺癌是第二常见的胰腺癌，发病率迅速增加。与白色患者相比，黑人pNET患者的生存率更差，与较小肿瘤相关的癌症扩散率更高。这些临床差异表明这两个患者组之间存在生物学差异。治疗pNET的指南主要基于白色患者的数据，可能不适用于黑人患者。在其他癌症中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，不同种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（将化学基团添加到DNA中以改变基因产物的生成），是环境因素，生活方式和压力可以影响个体基因的重要机制。已知pNET具有高比率的表观遗传失调。然而，对于黑人和白色患者之间pNET的（epi）遗传学差异一无所知，因为黑人患者占pNET遗传学研究中包括的患者的不到1%。来自不同患者群体的肿瘤如何与正常组织环境或患者的免疫系统相互作用之间可能存在其他关键差异。本项目的目标是调查黑人和白色pNET患者之间临床结局差异的原因。这些差异可能是在（epi）遗传水平，肿瘤如何与周围细胞相互作用，或环境影响。拟议的研究将比较两个患者群体之间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。这将证明临床结果差异是否可能是由于身体如何阻止肿瘤，并确定今天在南方腹地的黑人pNET患者群体中存在哪些关键压力源。虽然这项研究旨在了解表观遗传和基因表达变化影响黑人患者pNET的方式，但这些发现将深刻影响整个患者群体的pNET治疗和研究方向。