Abstract
Colorectal cancer (CRC) is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls) from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls) and 20 sera from Dundee, UK (10 CRC and 10 controls) were tested against a panel of multiple tumour-associated antigens (TAAs) using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19), stage II (n = 40), stage III (n = 34) and stage IV (n = 6) was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively), with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice.
Highlights
Colorectal cancer (CRC) is the second most common malignancy in the western world in terms of incidence and cancer-related mortality and carries a significant economic burden [1, 2]
Increased rates of completion of screening in an integrated care delivery system were achieved by adoption of the faecal immunochemical test (FIT) [14] and FIT can provide increased sensitivity compared to guaiac faecal occult blood tests (gFOBT) [15]
This study demonstrates the initial development of a robust, non-invasive blood test for detection of CRC with high sensitivity and specificity using a panel of selected tumour-associated antigens (TAAs); such a test doi:10.1371/journal.pone.0156971.g004
Summary
Colorectal cancer (CRC) is the second most common malignancy in the western world in terms of incidence and cancer-related mortality and carries a significant economic burden [1, 2]. The established non-invasive tests, such as the guaiac faecal occult blood tests (gFOBT), suffer from low sensitivity. Randomized, controlled trials have shown that annual or biennial fecal occult blood tests (FOBTs) are associated with a 15% to 33% decrease in CRC mortality rates following detection and appropriate intervention [7, 9,10,11]. This impact is limited by low patient acceptability of FOBT and low sensitivity and resulting in high interval cancer rates [12, 13]. Blood tests are likely to be more acceptable than stool tests in population-based screening [16]
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