Abstract
Colorectal cancer (CRC) is largely viewed as a preventable disease but the prevalence is increasing worldwide. Although many faecal and blood-based biomarkers have been proposed as potential diagnostic markers, none have been successful in large cohort studies. In this study, ELISA was used to evaluate 32 candidate protein biomarkers in a single cohort of CRC patients (n=95) and age/sex matched controls (n=50). Of these, 12 markers differed statistically between cases and controls. Receiver operating characteristic analysis identified IL8, Mac2BP, TIMP1, and OPN as the best performing markers for overall CRC diagnosis. However, further analysis determined that IL6, TGFB1, TIMP2 and IGF2 were most accurate at identifying early stage disease. We also assessed the correlation between markers and determined that the strongest correlations existed between VEGFA and TGFB1 (r=0.65, p<0.0001), M30 and M65 (r=0.59, p<0.001), and between TGFB1 and TIMP1 (r=0.55, p<0.0001). This analysis provides a consistent baseline for identifying a potential panel of diagnostic protein biomarkers in blood. Our results highlight protein biomarker combinations that reflect the disease process and which may provide the sensitivity and specificity required a reliable diagnosis of CRC.
Highlights
Worldwide, colorectal cancer (CRC) is the second most common cause of cancer-related death with an annual incidence over 1.2 million and an annual mortality over 600,000 [1]
The high frequency of CRC, the long time frame for its development and the observation that most CRC arise from pre-malignant polyps make CRC an ideal target for population screening programs where detection and removal of premalignant or early stage malignant disease (Stage A) can potentially prevent the occurrence of CRC or at least significantly increase the likelihood of a complete cure
The faecal occult blood test (FOBT) and faecal immunochemical test (FIT) are used to detect the presence of heme or blood in stool and whilst these tests have a relatively low cost, they are regarded as having poor sensitivity for early stage disease [8,9]
Summary
Colorectal cancer (CRC) is the second most common cause of cancer-related death with an annual incidence over 1.2 million and an annual mortality over 600,000 [1]. The high frequency of CRC, the long time frame for its development and the observation that most CRC arise from pre-malignant polyps make CRC an ideal target for population screening programs where detection and removal of premalignant (adenoma or polyp) or early stage malignant disease (Stage A) can potentially prevent the occurrence of CRC or at least significantly increase the likelihood of a complete cure. Identification of non-invasive biomarkers for early detection of CRC, including detection of pre-malignant and clinically significant polyps and adenomas, is important for reducing both incidence and mortality. The FOBT and FIT are used to detect the presence of heme or blood in stool and whilst these tests have a relatively low cost, they are regarded as having poor sensitivity for early stage disease [8,9]. Because the presence of blood in stool is not specific for CRC, the FOBT and FIT suffer from relatively high false positive rates. CA19-9 has limited utility as a diagnostic marker due to its lack of specificity for malignant disease [10]
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