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： 一组新的分子标记物在结直肠癌中的预后和预测价值 从非洲裔美国人（AA）和非西班牙裔高加索人中采集的结肠腺癌（CAC）组织 （白色）在MSM和UAB医院接受治疗的患者。该提案还旨在 发展塔斯基吉大学的初级教员特梅斯根·塞缪尔博士的职业生涯，他正在寻求更多的 了解癌症健康差异的基础。此外，该项目将继续 现有的成功合作，建立在目前资助的U 54伙伴关系奖， 博士莫尔豪斯医学院的哈维·邦珀斯和UAB的乌彭德·曼恩博士。初步 这些合作研究的结果表明，在侵袭性微卫星的基因表达谱的差异， 稳定（MSS）表型的CAC的AA和白人。根据这些发现，目前的假设是， AA和白人CACs的MSS表型不同，其在临床评估中的价值 结果随肿瘤分期和位置而变化。根据这一假设，Aim-1将评估结肠癌 来自447例AA和563例白人的标本，用于结肠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、疾病程度、肿瘤大小、肿瘤大小等相关。 复发、总体和疾病特异性生存期以及基于种族的治疗反应;目标2将 评估S100 A11和RPH 3AL在AA和白人CAC中的突变和表达状态， 突变状态和表达水平将与临床病理学特征和临床病理学特征相关。 AAs和白人的结果; Aim-3将确定S100 A11和RPH 3AL的机制功能 通过产生稳定抑制S100 A1或表达S100 A1的结肠癌细胞， RPH 3AL，三维肿瘤模型。 这些研究将确定AA的CAC的MSS表型的预测/预后分子特征 并具体阐明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.