Program Official

Principal Investigator

Robert S
Awardee Organization

University Of Tx Md Anderson Can Ctr
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Great Lakes New England Clinical Validation Center

The Great Lakes New England Clinical Validation Center (GLNE CVC), a Clinical Validation Consortium component of the Early Detection Research Network (EDRN) is a highly collaborative group of investigators whose aims to validate biomarkers for the early detection and risk assessment of cancers of the gastrointestinal tract. In this fifth competitive application, the GLNE continues to test the overall hypothesis that a panel of circulating and stool based biomarkers will increase the adherence to colorectal screening and in doing so reduce mortality caused by colorectal cancers. Based on the rising incidence of colorectal cancer (CRC) among adults age <50 in the US, and the low compliance and high mortality in underserved populations, increased emphasis is placed on these populations. The GLNE also proposes to continue its ongoing support of EDRN discovery priorities. We propose to address the following aims: (1) Primary Aim To expand and renew the archive of appropriately preserved stool, serum, plasma, urine, tissue and DNA biospecimens to be used by EDRN investigators for current and future validation and biomarker discovery research with expanded inclusion of subjects with early-onset CRC and underserved populations. This will allow assessment of the utility of individual stool-based, and serum-based biomarkers and biomarker panels for discriminating between individuals without neoplasia (subjects both at average and higher risk for developing colon cancer), and those with colon cancer or screen-relevant neoplasia (cancer plus advanced adenoma), and construction of panels of markers to discriminate between these groups. (2) To perform validation trials of promising biomarkers discovered by EDRN investigators, external collaborating institutions and collaborating EDRN industrial partners for the early detection of colorectal neoplasia. In this context we propose to (a) to clinically validate (via a methods comparison study) the performance of a point-of-care blood- based biomarker panel with the testing of serum/plasma samples obtained in clinics serving low-income and underserved communities and (b) to clinically validate an established 4-plex stool protein panel for early diagnosis of CRC. (3) To follow prospectively subjects enrolled in an established prospective Phase 2 validation trial to identify pre-diagnostic specimens which may be used to develop predictive markers.


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  • Yue T, Maupin KA, Fallon B, Li L, Partyka K, Anderson MA, Brenner DE, Kaul K, Zeh H, Moser AJ, Simeone DM, Feng Z, Brand RE, Haab BB. Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers. PloS one. 2011;6(12):e29180. Epub 2011 Dec 29. PMID: 22220206
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  • Tian Y, Denda-Nagai K, Tsukui T, Ishii-Schrade KB, Okada K, Nishizono Y, Matsuzaki K, Hafley M, Bresalier RS, Irimura T. Mucin 21 confers resistance to apoptosis in an O-glycosylation-dependent manner. Cell death discovery. 2022 Apr 11;8(1):194. PMID: 35410995
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  • Schwegler EE, Cazares L, Steel LF, Adam BL, Johnson DA, Semmes OJ, Block TM, Marrero JA, Drake RR. SELDI-TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma. Hepatology (Baltimore, Md.). 2005 Mar;41(3):634-42. PMID: 15726646
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  • Baxter NT, Ruffin MT 4th, Rogers MA, Schloss PD. Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions. Genome medicine. 2016 Apr 6;8(1):37. PMID: 27056827
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  • Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, Fontana RJ, Lok AS. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients. Hepatology (Baltimore, Md.). 2003 May;37(5):1114-21. PMID: 12717392
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  • Qiu Y, Patwa TH, Xu L, Shedden K, Misek DE, Tuck M, Jin G, Ruffin MT, Turgeon DK, Synal S, Bresalier R, Marcon N, Brenner DE, Lubman DM. Plasma glycoprotein profiling for colorectal cancer biomarker identification by lectin glycoarray and lectin blot. Journal of proteome research. 2008 Apr;7(4):1693-703. Epub 2008 Feb 27. PMID: 18311904
  • Poneros JM, Faye AS, Barr Fritcher EG, Sen A, Anandasabapathy S, Bresalier RS, Marcon N, Turgeon DK, Appelman H, Normolle D, Morrison LE, Brenner DE, Halling KC. A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett's Esophagus. Digestive diseases and sciences. 2017 May;62(5):1216-1222. Epub 2017 Mar 6. PMID: 28265829
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  • Miller CT, Moy JR, Lin L, Schipper M, Normolle D, Brenner DE, Iannettoni MD, Orringer MB, Beer DG. Gene amplification in esophageal adenocarcinomas and Barrett's with high-grade dysplasia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2003 Oct 15;9(13):4819-25. PMID: 14581353
  • Shaukat A, Marsh TL, Crockett SD, Syngal S, Bresalier RS, Brenner DE. Low Prevalence of Screen-Detected Colorectal Cancer in an Average-Risk Population: The New Normal. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Nov;20(11):2650-2652.e1. Epub 2021 Sep 20. PMID: 34547437
  • Rennert G, Kislitsin D, Brenner DE, Rennert HS, Lev Z. Detecting K-ras mutations in stool from fecal occult blood test cards in multiphasic screening for colorectal cancer. Cancer letters. 2007 Aug 18;253(2):258-64. Epub 2007 Mar 8. PMID: 17349741
  • Bresalier RS, Byrd JC, Tessler D, Lebel J, Koomen J, Hawke D, Half E, Liu KF, Mazurek N, Great Lakes-New England Clinical and Epidemiology Center of the Early Detection Research Network. A circulating ligand for galectin-3 is a haptoglobin-related glycoprotein elevated in individuals with colon cancer. Gastroenterology. 2004 Sep;127(3):741-8. PMID: 15362030
  • Su YH, Wang M, Brenner DE, Ng A, Melkonyan H, Umansky S, Syngal S, Block TM. Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer. The Journal of molecular diagnostics : JMD. 2004 May;6(2):101-7. PMID: 15096565
  • Cooper GS, Markowitz SD, Chen Z, Tuck M, Willis JE, Berger BM, Brenner DE, Li L. Performance of multitarget stool DNA testing in African American patients. Cancer. 2018 Oct 1;124(19):3876-3880. Epub 2018 Sep 7. PMID: 30193399
  • Yu M, O'Leary RM, Kaz AM, Morris SM, Carter KT, Chak A, Chandar A, Willis JE, Moinova HR, Markowitz SD, Brenner DE, Anandabapasathy S, Westerhoff M, Wong CJ, Shaheen NJ, Chen Y, Barnholtz-Sloan JS, Grady WM. Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015 Dec;24(12):1890-7. Epub 2015 Nov 6. PMID: 26545406
  • Baxter NT, Koumpouras CC, Rogers MA, Ruffin MT 4th, Schloss PD. DNA from fecal immunochemical test can replace stool for detection of colonic lesions using a microbiota-based model. Microbiome. 2016 Nov 14;4(1):59. PMID: 27842559

Clinical Trials

Study Name Clinical Trial ID
Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas NCT00843375
Preliminary Longitudinal Validation of Biomarkers Predictive of Barrett's Esophagus NCT00844077