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.

Public Health Relevance

Molecular signatures identified in this project will be useful in diagnosing aggressive forms of colon cancers and provide a basis for future validation studies;and, eventually, aid in minimizing the disparity In mortality of AA patients with colon cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA118638-08
Application #
8568033
Study Section
Special Emphasis Panel (ZCA1-SRLB-Y)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
8
Fiscal Year
2013
Total Cost
$16,441
Indirect Cost
$7,293
Name
Morehouse School of Medicine
Department
Type
DUNS #
102005451
City
Atlanta
State
GA
Country
United States
Zip Code
30310
Mullen, McKay; Gonzalez-Perez, Ruben Rene (2016) Leptin-Induced JAK/STAT Signaling and Cancer Growth. Vaccines (Basel) 4:
Kapur, Neeraj; Mir, Hina; Clark Iii, Clarence E et al. (2016) CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition. Br J Cancer 114:1343-51
Zhang, Wei; Yi, Bin; Wang, Chao et al. (2016) Silencing of CD24 Enhances the PRIMA-1-Induced Restoration of Mutant p53 in Prostate Cancer Cells. Clin Cancer Res 22:2545-54
Chowdhury, Indrajit; Thomas, Kelwyn; Thompson, Winston E (2016) Prohibitin( PHB) roles in granulosa cell physiology. Cell Tissue Res 363:19-29
Kaur, Punit; Aliru, Maureen L; Chadha, Awalpreet S et al. (2016) Hyperthermia using nanoparticles--Promises and pitfalls. Int J Hyperthermia 32:76-88
Lipsey, Crystal C; Harbuzariu, Adriana; Daley-Brown, Danielle et al. (2016) Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer. World J Methodol 6:43-55
Holden, Kisha; Charles, Lisa; King, Stephen et al. (2015) Reducing Health Disparities and Improving Health Equity in Saint Lucia. Int J Environ Res Public Health 13:ijerph13010037
McGregor, Brian; Mack, Dominic; Wrenn, Glenda et al. (2015) Improving Service Coordination and Reducing Mental Health Disparities Through Adoption of Electronic Health Records. Psychiatr Serv 66:985-7
Smith, Selina A; Sheats, Joyce Q; Whitehead, Mary S et al. (2015) Developing a Cookbook with Lifestyle Tips: A Community-Engaged Approach to Promoting Diet-Related Cancer Prevention Guidelines. Jacobs J Food Nutr 2:
Lokko, Carl; Turner, Jacquelyn; Yoo, Wonsuk et al. (2015) Anal Squamous Cell Carcinoma in African Americans with and without HIV: A Comparative Study. J Cancer Epidemiol Treat 1:6-10

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