Molecular Characterization of Aggressive Colon Cancers of African-American.......

MSM/TU/UAB伙伴关系的这个完整项目建议在以下领域进行临床前翻译研究 一组新的分子标志物在结直肠癌中的预后和预测价值 结肠腺癌(CAC)组织来自非裔美国人(AA)和非西班牙裔高加索人 (白色)在MSM和UAB医院接受治疗的患者。这项提议还意在 发展塔斯基吉大学初级教员特梅斯根·塞缪尔博士的职业生涯，他正在寻求更多 了解癌症健康差异的基础的经验。此外，该项目将继续 在目前资助的U54伙伴关系奖期间建立的现有成功合作， 莫尔豪斯医学院的哈维·邦珀斯博士和UAB的Upender Manne博士。预赛 这些合作研究的结果显示，攻击性微卫星的基因表达谱存在差异。 AAS和白人CACs的稳定表型(MSS)。基于这些发现，目前的假设是 AAS和白人CAC的MSS表型不同及其在临床评估中的价值 结果因肿瘤分期和位置不同而不同。根据这一假设，AIM-1将评估结肠癌 447例AA和563例白人结肠组织差异表达基因的表达谱研究 具有MSS表型的癌症。表达谱将与肿瘤分期、疾病相关 复发、总存活率和疾病特异性存活率，以及基于种族的治疗反应；AIM-2将 检测S100A11和RPH3AL在AAS和白人CACs中的突变和表达状况，以及 突变状态和表达水平将与临床病理特征和临床相关 AAS和白色蛋白的结果；AIM-3将决定S100A11和RPH3AL的机制功能 在体外培养的结肠癌细胞中稳定抑制S100A1或表达S100A1 RPH3AL，在三维肿瘤模型中。 这些研究将确定AAS CACs的MSS表型的预测/预后分子特征 并具体阐明AAS和白人结肠癌发生的分子机制。

This Full Project of the MSM/TU/UAB Partnership proposes to conduct preclinical translational studies in colorectal cancer to determine the prognostic and predictive value of a panel of novel molecular markers in colonic adenocarcinoma (CAC) tissues collected from African-American (AA) and non-Hispanic Caucasian (white) patients who underwent treatment at MSM and UAB hospitals. This proposal is also intended to develop the career of Dr. Temesgen Samuel, a junior faculty at Tuskegee Univeristy, who is seeking more experience in understanding the basis for cancer health disparities. Further, this project will continue the existing successful collaboration, established during the currently funded U54 Partnership award, between Dr. Harvey Bumpers of Morehouse School of Medicine and Dr. Upender Manne of UAB. The preliminary results of these collaborative studies show a disparity in gene expression profiles of aggressive microsatellite stable (MSS) phenotypes of CACs of AAs and whites. Based on these findings, the current hypothesis is that the MSS phenotypes of CACs from AAs and whites are different, and their value in assessing the clincal outcomes varies with tumor stage and location. To this hypothesis, Aim-1 will evaluate colon cancer specimens from 447 AAs and 563 whites for expression profiles of genes differentially expressed in colon cancers with MSS phenotypes. The expression profiles will be correlated with tumor stage, disease recurrence, overall and disease-specific survival, and response to therapy based on ethnicity; Aim-2 will assess the mutational and expression status of S100A11 and RPH3AL in CACs of AAs and whites, and the mutational status and expression levels will be correlated with clinicopatholgoic features and with the clinical outcomes of AAs and whites; and Aim-3 will determine the mechanistic functions of S100A11 and RPH3AL in colon cancer cells in vitro by generating colon cancer cells stably inhibiting S100A1 or expressing RPH3AL, in 3-dimensional tumor models. These studies will identify predictive/prognostic molecular signatures of MSS phenotypes of CACs of AAs and specifically elucidate the underiying molecular mechanisms of colon cancers of AAs and whites.