title: Serum proteomic profiling for the early diagnosis of colorectal cancer.
abstract: No ideal serum biomarker currently exists for the early diagnosis of colorectal cancer (CRC). Magnetic bead-based fractionation coupled with MALDI-TOF MS was used to screen serum samples from CRC patients, healthy controls, and other cancer patients. A diagnostic model with five proteomic features (m/z 1778.97, 1866.16, 1934.65, 2022.46, and 4588.53) was generated using Fisher algorithm with best performance. The Fisher-based model could discriminate CRC patients from the controls with 100% (46/46) sensitivity and 100% (35/35) specificity in the training set, 95.6% (43/45) sensitivity and 83.3% (35/42) specificity in the test set. We further validated the model with 94.4% (254/269) sensitivity and 75.5% (83/110) specificity in the external independent group. In other cancers group, the Fisher-based model classified 25 of 46 samples (54.3%) as positive and the other 21 as negative. With FT-ICR-MS, the proteomic features of m/z 1778.97, 1866.16, 1934.65, and 2022.46, of which intensities decreased significantly in CRC, were identified as fragments of complement C3f. Therefore, the Fisher-based model containing five proteomic features was able to effectively differentiate CRC patients from healthy controls and other cancers with a high sensitivity and specificity, and may be CRC-specific. Serum complement C3f, which was significantly decreased in CRC group, may be relevant to the incidence of CRC.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Wei
authors.forename: Yunshi
authors.initials: Y
authors.lastname: Zhong
authors.forename: Xinzhe
authors.initials: X
authors.lastname: Yu
authors.forename: Shenyong
authors.initials: S
authors.lastname: Zhai
authors.forename: Jianmin
authors.initials: J
authors.lastname: Xu
authors.forename: Xinyu
authors.initials: X
authors.lastname: Qin
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001798:Blood Proteins / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis; D003179:Complement C3b / Q000302:isolation & purification / Q000378:metabolism; D055088:Early Detection of Cancer; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; C046821:complement C3f; D003179:Complement C3b