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PP-55

Quantitative Proteomic Analysis Reveals Up-Regulation of Type I Collagen During Tumorigenesis of Colorectal Cancer

초록

영어

Colorectal cancer (CRC) is one of the most prevalent cancers in the world with high mortality and morbidity rates. In this study, we have performed comparative proteomic profiling of sera from CRC patients at stage I (n=17), stage II (n=40), stage III (n=24) and healthy subjects (n=25) to gain a global view of protein expression change during CRC tumorigenesis and provide potential targets for CRC diagnosis and treatment. As a result, a total of 93 proteins were found differentially expressed in CRC patients with a label-free quantitative APXE method. After GO and KEGG pathway analysis, those proteins most frequently involved in ECM-receptor interaction, complement and coagulation cascades. As important as components of ECM, we found several collagens in CRC serum had been changed from tumor stage I to IV. And the validation of collagen I (COL1) at RNA and protein expression level shown extremely comparable to pooled serum proteomic results using independent 26 paired tumor and matched normal colorectal tissues. Those findings indicated that the change of collagen I observed in serum were indeed from pathogenic lesion of colorectal tissue. Moreover, we further investigated serum levels of COL1, PICP (the synthesis indicator) and CTx (the breakdown indicator) in 77 CRC patients and 33 normal controls by ELISA. The results showed PICP and CTx were better for discriminating normal from cancer groups as well as non-metastatic from metastatic tumor than COL1. Finally, we evaluated the expression of MMPs in paired tumor and normal tissues from patients with different stages. Notably, the expression of MMP1, 7 and 14 were remarkably enhanced in carcinoma tissues and the trend were parallel with the progression of tumor stage. The expression of E-cadherin and CDX2, which had been considered as targets of COL1 in cell models, were also verified in tissues and displayed decrease in tumor. Overall, COL1 might be affected by MMP1, 7, 14 and had effects on cell adhesion and differentiation through E-cadherin and CDX2.

저자정보

  • Xia Zou Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
  • Bo Feng Department of Surgery, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai, 200025, China
  • Taotao Dong Department of Surgery, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai, 200025, China
  • Binbin Tan Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
  • Hao Shen Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
  • Xiu Zhang Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
  • Menghui Zhang Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
  • Minhua Zheng Department of Surgery, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai, 200025, China
  • Yan Zhang Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China

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