BACKGROUND: The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. OBJECTIVE: To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. DESIGN: Case-control study. SETTING: Colonoscopy-controlled referral population from several centers. PARTICIPANTS: 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). MEASUREMENTS: Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. RESULTS: In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001). LIMITATION: Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples. CONCLUSION: Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening. PRIMARY FUNDING SOURCE: Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.
BACKGROUND: The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. OBJECTIVE: To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. DESIGN: Case-control study. SETTING: Colonoscopy-controlled referral population from several centers. PARTICIPANTS: 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). MEASUREMENTS: Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. RESULTS: In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001). LIMITATION: Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples. CONCLUSION: Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening. PRIMARY FUNDING SOURCE: Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.
Authors: Gilbert S Omenn; Lydie Lane; Christopher M Overall; Fernando J Corrales; Jochen M Schwenk; Young-Ki Paik; Jennifer E Van Eyk; Siqi Liu; Michael Snyder; Mark S Baker; Eric W Deutsch Journal: J Proteome Res Date: 2018-08-23 Impact factor: 4.466
Authors: Víctor Segura; M Luz Valero; Laura Cantero; Javier Muñoz; Eduardo Zarzuela; Fernando García; Kerman Aloria; Javier Beaskoetxea; Jesús M Arizmendi; Rosana Navajas; Alberto Paradela; Paula Díez; Rosa Mª Dégano; Manuel Fuentes; Alberto Orfao; Andrés García Montero; Alba Garin-Muga; Fernando J Corrales; Manuel M Sánchez Del Pino Journal: Proteomes Date: 2018-02-05
Authors: L J W Bosch; V Melotte; S Mongera; K L J Daenen; V M H Coupé; S T van Turenhout; E M Stoop; T R de Wijkerslooth; C J J Mulder; C Rausch; E J Kuipers; E Dekker; M J Domanico; G P Lidgard; B M Berger; M van Engeland; B Carvalho; G A Meijer Journal: Am J Gastroenterol Date: 2019-12 Impact factor: 10.864
Authors: Malgorzata A Komor; Meike de Wit; Jose van den Berg; Sanne R Martens de Kemp; Pien M Delis-van Diemen; Anne S Bolijn; Marianne Tijssen; Tim Schelfhorst; Sander R Piersma; Davide Chiasserini; Joyce Sanders; Christian Rausch; Youri Hoogstrate; Andrew P Stubbs; Mark de Jong; Guido Jenster; Beatriz Carvalho; Gerrit A Meijer; Connie R Jimenez; Remond J A Fijneman Journal: Int J Cancer Date: 2019-08-30 Impact factor: 7.396
Authors: Malgorzata A Komor; Linda Jw Bosch; Veerle Mh Coupé; Christian Rausch; Thang V Pham; Sander R Piersma; Sandra Mongera; Chris Jj Mulder; Evelien Dekker; Ernst J Kuipers; Mark A van de Wiel; Beatriz Carvalho; Remond Ja Fijneman; Connie R Jimenez; Gerrit A Meijer; Meike de Wit Journal: J Pathol Date: 2020-01-13 Impact factor: 7.996
Authors: Tiansheng Zhu; Yi Zhu; Yue Xuan; Huanhuan Gao; Xue Cai; Sander R Piersma; Thang V Pham; Tim Schelfhorst; Richard R G D Haas; Irene V Bijnsdorp; Rui Sun; Liang Yue; Guan Ruan; Qiushi Zhang; Mo Hu; Yue Zhou; Winan J Van Houdt; Tessa Y S Le Large; Jacqueline Cloos; Anna Wojtuszkiewicz; Danijela Koppers-Lalic; Franziska Böttger; Chantal Scheepbouwer; Ruud H Brakenhoff; Geert J L H van Leenders; Jan N M Ijzermans; John W M Martens; Renske D M Steenbergen; Nicole C Grieken; Sathiyamoorthy Selvarajan; Sangeeta Mantoo; Sze S Lee; Serene J Y Yeow; Syed M F Alkaff; Nan Xiang; Yaoting Sun; Xiao Yi; Shaozheng Dai; Wei Liu; Tian Lu; Zhicheng Wu; Xiao Liang; Man Wang; Yingkuan Shao; Xi Zheng; Kailun Xu; Qin Yang; Yifan Meng; Cong Lu; Jiang Zhu; Jin'e Zheng; Bo Wang; Sai Lou; Yibei Dai; Chao Xu; Chenhuan Yu; Huazhong Ying; Tony K Lim; Jianmin Wu; Xiaofei Gao; Zhongzhi Luan; Xiaodong Teng; Peng Wu; Shi'ang Huang; Zhihua Tao; Narayanan G Iyer; Shuigeng Zhou; Wenguang Shao; Henry Lam; Ding Ma; Jiafu Ji; Oi L Kon; Shu Zheng; Ruedi Aebersold; Connie R Jimenez; Tiannan Guo Journal: Genomics Proteomics Bioinformatics Date: 2020-08-12 Impact factor: 7.691