IGFBP-1 As a Serum Protein Biomarker for Early Detection of Gastrointestinal Cancer

Abstract

Background: Early detection would significantly improve cancer prognosis. We aimed to identify serum protein biomarker for early cancer detection and assess the diagnostic value in various types of cancers. Methods: We performed a three-stage study, and recruited participants of normal controls and seven different types of cancer patients (oesophageal squamous cell carcinoma (ESCC), oesophagogastric junction adenocarcinoma (EJA), stomach cancer, colorectal cancer, lung cancer, nasopharyngeal cancer and breast cancer) from two medical centres. We applied two different antibody arrays to screen candidate serum protein which were increased in 20 ESCC patients compared with 20 matched normal controls. In biomarker assessment stage, the diagnostic value of the selected protein measured by ELISA was evaluated in seven cancer types, and was validated in two independent cohorts of ESCC patients and controls (cohorts 1 and 2). Receiver operating characteristics (ROCs) with the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to calculate diagnostic accuracy. Findings: We recruited 1628 participants to biomarker assessment stage: 287 with ESCC, 237 with EJA, 207 with stomach cancer, 138 with colorectal cancer, 126 with lung cancer, 150 with nasopharyngeal cancer, 150 with breast cancer and 333 normal controls, and 472 and 452 participants comprised of ESCC patients and controls to the two independent validation cohorts. Serum IGFBP-1 showed elevated level for ESCC in both antibody arrays. A significant increase in the serum IGFBP-1 level on all cancer types except breast cancer was confirmed by ELISA, compared with normal controls. Serum IGFBP-1 provided a high diagnostic accuracy of gastrointestinal tumours (AUC 0·880-0·938, sensitivity 65·22-77·22%, and specificity 90·39%). Similar results were noted for early-stage gastrointestinal tumours (0·858-0·936, 60·29-83·93%, and 90·39%). In two validation cohorts, serum IGFBP-1 maintained diagnostic performance for early stage ESCC (0·849, 68·04%, and 89·09% in cohort 1, and 0·911, 72·34% and 87·37% in cohort 2). Furthermore, when compared with CEA, Cyfra21-1 and SCCA tested alone or together, serum IGFBP-1 had significantly improved diagnostic accuracy for ESCC and early stage ESCC. Interpretation: Serum IGFBP-1 is a potential biomarker with high diagnostic value for the early detection of gastrointestinal cancer. Funding Statement: This work was supported by funding from the Natural Science Foundation of China (31600632, 81772532 and 81872372), the Population-based prospective cohort study of esophageal cancer and precancerous lesions in high risk areas (2016YFC0901404), the National Cohort of Esophageal Cancer of China (2016YFC0901400), and the Guangdong Esophageal Cancer Institute Science and Technology Program (M201713), the Natural Science Foundation of Guangdong Province (2018A030307079) and the Shantou University Medical College Clinical Research Enhancement Initiative (201428). Declaration of Interests: We declare that we have no conflicts of interest. Ethics Approval Statement: The study was approved by the Institutional Review Boards for Human Research at each hospital, and informed consent was obtained from all participants.