Microarray-based Simultaneous Quantitation of Six Serum Tumor Markers Improves Cancer Diagnostics
DOI:
https://doi.org/10.12974/2311-8792.2014.02.02.1Keywords:
Cancer diagnostics, logistic regression, protein microarrays, ROC analysis, tumor markers.Abstract
Relative low sensitivity and specificity of the known protein tumor markers limit their application in cancer diagnosis and screening. Simultaneous use of their combination can improve diagnostic efficacy. The aim of the study was to estimate diagnostic characteristics of the hydrogel microarray-based test system “TM-Biochip” developed in EIMB RAS for a simultaneous quantitation of six tumor markers: alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA total and free), neuron-specific enolase (NSE) and human chorionic gonadotropin (hCG) and to compare them with the diagnostic characteristics of systems used for estimating one tumor marker. Diagnostic performance of “TM-Biochip” system was evaluated using 170 serum samples from clinically confirmed cancer patients and control group patients. To evaluate the diagnostic efficiency of the test system we used linear regression and multiple logistic regression (LR), receiver operating characteristic (ROC) curve analysis and area under ROC curves (AUC). It was demonstrated that this new diagnostic system allows assessing the level of each marker and gives data comparable with the results obtained by measurement of each individual marker in a respective conventional ELISA system. ROC analysis and evaluation of diagnostic sensitivity and specificity of the system demonstrated that the new system did better than each of individual markers when classified: (1) cancer patients vs non-cancer patients; (2) patients with colorectal cancer (CRC) vs the other patients: patients with the other cancers and non-cancer patients; (3) patients with CRC vs patients with the other malignant tumors and (4) patients with prostate cancer (PC) vs patients with benign prostatic hyperplasia (BPH). In classification of the patients with PC and the patients with BPH AUC for the combination of six markers (LR6) was significantly higher than AUCs for each of individual markers, including the greatest AUC for PSAt (0.894 vs 0.771, p=0.032). On addition of such parameter as “age of patient” to the combination of six markers (LR7), AUC raised till 0.930 (p=0.01). Specificity at 90% sensitivity for PSAt, LR6 and LR7 accounted for 20 % (5.7-43.7), 60% (36.1-80.9) and 80.6 % (55.5-95.0), respectively. These results showed that “TM-Biochip” system is more efficient in revealing of cancer patients.
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