MAPRE1 as a plasma biomarker for early-stage colorectal cancer and adenomas.
Blood-based biomarkers for early detection of colorectal cancer could complement current approaches to colorectal cancer screening. We previously identified the APC-binding protein MAPRE1 as a potential colorectal cancer biomarker. Here, we undertook a case-control validation study to determine the performance of MAPRE1 in detecting early colorectal cancer and colon adenoma and to assess the potential relevance of additional biomarker candidates. We analyzed plasma samples from 60 patients with adenomas, 30 with early colorectal cancer, 30 with advanced colorectal cancer, and 60 healthy controls. MAPRE1 and a set of 21 proteins with potential biomarker utility were assayed using high-density antibody arrays, and carcinoembryonic antigen (CEA) was assayed using ELISA. The biologic significance of the candidate biomarkers was also assessed in colorectal cancer mouse models. Plasma MAPRE1 levels were significantly elevated in both patients with adenomas and patients with colorectal cancer compared with controls (P < 0.0001). MAPRE1 and CEA together yielded an area under the curve of 0.793 and a sensitivity of 0.400 at 95% specificity for differentiating early colorectal cancer from controls. Three other biomarkers (AK1, CLIC1, and SOD1) were significantly increased in both adenoma and early colorectal cancer patient plasma samples and in plasma from colorectal cancer mouse models at preclinical stages compared with controls. The combination of MAPRE1, CEA, and AK1 yielded sensitivities of 0.483 and 0.533 at 90% specificity and sensitivities of 0.350 and 0.467 at 95% specificity for differentiating adenoma and early colorectal cancer, respectively, from healthy controls. These findings suggest that MAPRE1 can contribute to the detection of early-stage colorectal cancer and adenomas together with other biomarkers.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. ataguchi@mdanderson.org.
Ayumu
A
Taguchi
Translational Research Program, Human Biology and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Jung-Hyun
JH
Rho
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Qingxiang
Q
Yan
Translational Research Program, Human Biology and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Yuzheng
Y
Zhang
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Yang
Y
Zhao
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Hanwen
H
Xu
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Satyendra Chandra
SC
Tripathi
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Hong
H
Wang
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan. VA Medical Center, Ann Arbor, Michigan.
Dean E
DE
Brenner
Department of Genetics, Harvard Medical School, Boston, Massachusetts.
Melanie
M
Kucherlapati
Department of Genetics, Harvard Medical School, Boston, Massachusetts.
Raju
R
Kucherlapati
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Adam T
AT
Boutin
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Y Alan
YA
Wang
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ronald A
RA
DePinho
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ziding
Z
Feng
Translational Research Program, Human Biology and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Paul D
PD
Lampe
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Samir M
SM
Hanash
D000236:Adenoma / Q000097:blood*; D000263:Adenylate Kinase / Q000097:blood; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000097:blood*; D012372:ROC Curve; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C500985:MAPRE1 protein, human; C000610767:MAPRE1 protein, mouse; D008869:Microtubule-Associated Proteins; D000263:Adenylate Kinase; C110939:adenylate kinase 1