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A blood‐based biomarker panel for stratifying current risk for colorectal cancer
Author(s) -
Marshall Kenneth Wayne,
Mohr Steve,
Khettabi Faysal El,
Nossova Nadejda,
Chao Samuel,
Bao Weisheng,
Ma Jun,
Li XiaoJun,
Liew ChoongChin
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24910
Subject(s) - medicine , biomarker , colorectal cancer , oncology , population , receiver operating characteristic , risk assessment , cancer , genetics , biology , computer science , environmental health , computer security
Colorectal cancer (CRC) is often curable and preventable using current screening modalities. Unfortunately, screening compliance remains low, partly due to patient dissatisfaction with faecal/endoscopic testing. Recent guidelines advise CRC screening should begin with risk stratification. A blood‐based test providing clinically actionable CRC risk information would likely improve screening compliance and enhance clinical decision making. We analyzed 196 gene expression profiles to select candidate CRC biomarkers. qRT‐PCR was performed on 642 samples to develop a 7‐gene biomarker panel using 112 CRC/120 controls (training set) and 202 CRC/208 controls (independent, blind test set). Panel performance characteristics and disease prevalence (0.7%) were then used to develop a scale assessing an individual's current risk of having CRC based on his/her gene signature. A 7‐gene panel ( ANXA3, CLEC4D, LMNB1, PRRG4, TNFAIP6, VNN1 and IL2RB ) discriminated CRC in the training set (area under the receiver‐operating‐characteristic curve (ROC AUC), 0.80; accuracy, 73%; sensitivity, 82%; specificity 64%). The independent blind test set confirmed performance (ROC AUC, 0.80; accuracy, 71%; sensitivity, 72%; specificity, 70%). Individual gene profiles were compared against the population results and used to calculate the current relative risk for CRC. We have developed a 7‐gene, blood‐based biomarker panel that can stratify subjects according to their current relative risk across a broad range in an average‐risk population. Across the continuous spectrum of risk as defined by the current relative risk scale, it is possible to identify clinically meaningful reference points that can assist patients and physicians in CRC screening decision making.