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

MSM/TU/UAB 合作伙伴关系的这个完整项目建议在以下领域进行临床前转化研究： 结直肠癌，以确定一组新型分子标记物的预后和预测价值 从非裔美国人 (AA) 和非西班牙裔白种人采集的结肠腺癌 (CAC) 组织 （白色）在 MSM 和 UAB 医院接受治疗的患者。该提案还旨在 塔斯基吉大学的初级教师 Temesgen Samuel 博士正在寻求更多的职业发展机会 了解癌症健康差异基础的经验。此外，该项目还将继续 在目前资助的 U54 合作伙伴奖期间建立的现有成功合作， 莫尔豪斯医学院的 Harvey Bumpers 博士和阿拉巴马大学的 Upender Manne 博士。初步的 这些合作研究的结果表明，攻击性微卫星的基因表达谱存在差异 AA 和白人 CAC 的稳定 (MSS) 表型。基于这些发现，目前的假设是 AA 和白人 CAC 的 MSS 表型不同，其在评估临床表现方面的价值 结果因肿瘤分期和位置而异。根据这一假设，Aim-1 将评估结肠癌 来自 447 个 AA 和 563 个白色样本的结肠中差异表达基因的表达谱 具有 MSS 表型的癌症。表达谱将与肿瘤分期、疾病相关 复发率、总体生存率和疾病特异性生存率以及基于种族的治疗反应； Aim-2将 评估 AA 和白人 CAC 中 S100A11 和 RPH3AL 的突变和表达状态，以及 突变状态和表达水平将与临床病理特征和临床症状相关。 AA 和白人的结果； Aim-3将确定S100A11和RPH3AL的机械功能 通过产生稳定抑制 S100A1 或表达 S100A1 的结肠癌细胞，在体外结肠癌细胞中 RPH3AL，3 维肿瘤模型。 这些研究将确定 AA 的 CAC MSS 表型的预测/预后分子特征 并具体阐明了 AA 和白人结肠癌的潜在分子机制。

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.