Lei Liu1, Yecai Huang2, Yan Li3, Qiong Wang4, Yaying Hao5, Lüye Liu5, Xue Yao6, Xiuju Yao7, Yi Wei8, Xiaobin Sun9, Yuanbiao Guo10. 1. Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, 29 Xifu North Street, Chengdu, 610031, Sichuan, China. Liuleilei118@163.com. 2. Department of Radiation Oncology, School of Medicine, University of Electronic Science and Technology of China, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, 610042, Sichuan, China. 3. Department of General Surgery, The 77th Army Hospital, Leshan, 614000, Sichuan, China. 4. Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, 82 Qinglong Road, Chengdu, 610031, Sichuan, China. 5. Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, 29 Xifu North Street, Chengdu, 610031, Sichuan, China. 6. Southwest Jiaotong University College of Medicine, Southwest Jiaotong University Affiliated Chengdu Third People's Hospital, Chengdu, 610036, Sichuan, China. 7. Department of Laboratory, 363 Hospital, Chengdu, 610041, Sichuan, China. 8. Department of Clinical Laboratory, The Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, 610051, Sichuan, China. 9. Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, 82 Qinglong Road, Chengdu, 610031, Sichuan, China. xbsun1197@163.com. 10. Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, 29 Xifu North Street, Chengdu, 610031, Sichuan, China. Guo.ybiao@yahoo.com.
Abstract
PURPOSE: Colorectal cancer (CRC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of CRC. The aim of the present study was to screen candidate biomarkers in diagnosis and prognosis of CRC based on a novel strategy. MATERIALS AND METHODS: The expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as "positive", and the top 10% genes with "positive rate" were filtered out as candidate diagnostic biomarkers in four Gene Expression Omnibus (GEO) datasets. Then, the prognostic value of candidate biomarkers was estimated Cox regression analysis. Moreover, the concentration of biomarker in serum was detected in CRC patients. RESULTS: Eighteen candidate biomarkers were identified with efficient diagnostic value in CRC. As a prognostic biomarker, FJX1 (four-jointed box kinase 1) showed a good performance in predicting overall survivals in CRC patients. In serum levels, FJX1 showed high sensitivity and specificity in distinguishing CRC patients from controls, and the concentration of serum FJX1 was associated with distant metastasis in CRC. In addition, serum FJX1 was significantly decreased after surgery in CRC patients. Compared with traditional CRC biomarkers CEA and CA 19-9, FJX1 still showed good efficiency in diagnosis and prognosis. Moreover, inhibition of FJX1 expression by siRNA or neutralization of secreted FJX1 by antibody could suppress cell proliferation and migration in vitro. CONCLUSION: Our findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that FJX1 was a candidate diagnostic and prognostic biomarker in CRC patients.
PURPOSE: Colorectal cancer (CRC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of CRC. The aim of the present study was to screen candidate biomarkers in diagnosis and prognosis of CRC based on a novel strategy. MATERIALS AND METHODS: The expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as "positive", and the top 10% genes with "positive rate" were filtered out as candidate diagnostic biomarkers in four Gene Expression Omnibus (GEO) datasets. Then, the prognostic value of candidate biomarkers was estimated Cox regression analysis. Moreover, the concentration of biomarker in serum was detected in CRC patients. RESULTS: Eighteen candidate biomarkers were identified with efficient diagnostic value in CRC. As a prognostic biomarker, FJX1 (four-jointed box kinase 1) showed a good performance in predicting overall survivals in CRC patients. In serum levels, FJX1 showed high sensitivity and specificity in distinguishing CRC patients from controls, and the concentration of serum FJX1 was associated with distant metastasis in CRC. In addition, serum FJX1 was significantly decreased after surgery in CRC patients. Compared with traditional CRC biomarkers CEA and CA 19-9, FJX1 still showed good efficiency in diagnosis and prognosis. Moreover, inhibition of FJX1 expression by siRNA or neutralization of secreted FJX1 by antibody could suppress cell proliferation and migration in vitro. CONCLUSION: Our findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that FJX1 was a candidate diagnostic and prognostic biomarker in CRC patients.
Authors: W S Wang; J K Lin; T J Chiou; J H Liu; F S Fan; C C Yen; T C Lin; J K Jiang; S H Yang; H S Wang; P M Chen Journal: Jpn J Clin Oncol Date: 2000-01 Impact factor: 3.019