Abstract
The early detection of colorectal cancer (CRC) is crucial for successful treatment and patient survival. However, compliance with current screening methods remains poor. This study aimed to identify an accurate blood-based gene expression signature for CRC detection. Gene expression in peripheral blood samples from 216 patients with CRC tumors and 187 controls was investigated in the study. We first conducted a microarray analysis to select candidate genes that were significantly differentially expressed between patients with cancer and controls. A quantitative reverse transcription PCR assay was then used to evaluate the expression of selected genes. A gene expression signature was identified using a training set (n = 200) and then validated using an independent test set (n = 160). We identified an 18-gene signature that discriminated the patients with CRC from controls with 92% accuracy, 91% sensitivity, and 92% specificity. The signature performance was further validated in the independent test set with 86% accuracy, 84% sensitivity, and 88% specificity. The area under the receiver operating characteristics curve was 0.94. The signature was shown to be enriched in genes related to immune functions. This study identified an 18-gene signature that accurately discriminated patients with CRC from controls in peripheral blood samples. Our results prompt the further development of blood-based gene expression biomarkers for the diagnosis and early detection of CRC.
Highlights
Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related mortality worldwide [1]
We identified an 18-gene signature that discriminated the patients with CRC from controls with 92% accuracy, 91% sensitivity, and 92% specificity
Our results prompt the further development of blood-based gene expression biomarkers for the diagnosis and early detection of CRC
Summary
Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related mortality worldwide [1]. In 2008, more than 1 million cases were newly diagnosed and more than 600,000 people died from the disease [2]. Given its slow development from removable precancerous lesions and curable early stages, screening for CRC has the potential to reduce both the incidence and mortality of the disease [3]. The available screening tools include fecal occult blood testing. Authors' Affiliations: 1Department of Oncology, Shanghai Medical College; 2Institute of Biomedical Sciences; 3Institute of Pathology, Fudan University; Departments of 4Colorectal Surgery and 5Pathology, Fudan University Shanghai Cancer Center; 6Fudan University Shanghai Cancer Center—Institut Merieux Laboratory; and 7bioMerieux (Shanghai) Co., Ltd., Shanghai, China. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
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