Human Blood Autoantibodies in the Detection of Colorectal Cancer.
Human Blood Autoantibodies in the Detection of Colorectal Cancer.
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DOI：
10.1371/journal.pone.0156971
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sewell HF
中科院分区：
文献类型：
--
作者：
Negm OH;Hamed MR;Schoen RE;Whelan RL;Steele RJ;Scholefield J;Dilnot EM;Shantha Kumara HM;Robertson JF;Sewell HF
结直肠癌（CRC）是西方世界第二常见的恶性肿瘤。所有癌症类型的早期检测和诊断对于改善预后至关重要，因为当肿瘤应该是可切除和可治愈的时，可以进行早期治疗。使用优化的多重微阵列系统，针对一组多种肿瘤相关抗原（TAA）检测来自3个不同队列的血清;来自美国纽约的42份血清（21份CRC和21份匹配对照）、来自美国匹兹堡的200份血清（100份CRC和100份对照）和来自英国邓迪的20份血清（10份CRC和10份对照）。针对每个样品的内部IgG标准曲线内插TAA特异性IgG应答。在每个队列中检查个体TAA特异性应答，以确定稳健初始评分方法的临界值，从而确定灵敏度和特异性。TAAs组合的灵敏度和特异性在癌症阳性和正常血清之间提供了良好的区分。针对一组32种TAA检测的样本集的总体灵敏度和特异性对于6种抗原分别为61.1%和80.9%; p53、AFP、KRAS、Annexin、RAF 1和NY-CO 16。此外，匹兹堡样本集在不同临床分期的CRC中观察到的灵敏度相似; I期（n = 19）、II期（n = 40）、III期（n = 34）和IV期（n = 6）（分别为73.6%、75.0%、73.5%和83.3%），右侧和左侧CRC的灵敏度水平相似。我们确定了一个足够的灵敏度和特异性的抗原面板CRC的早期检测，基于血清分析的自身抗体反应，使用强大的多重抗原微阵列技术。这为筛查和检测早期结直肠癌的血液检测提供了可能性。然而，在将其用于临床实践之前，该面板将需要进一步的验证研究。
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.