Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide and has poor prognosis. To identify the oncofetal proteins involved in CRC carcinogenesis, differentially expressed proteins among fetal colorectal tissues, CRC, and the paired tumor-adjacent normal colorectal tissues were investigated by a two-dimensional gel electrophoresis and MALDI-TOF/TOF-based proteomics approach. 42 protein spots were differentially expressed among these tissues, and 22 proteins were identified by MS analysis. Desmin and zinc finger protein 829 were found to be elevated in CRC tissue and fetal colorectal tissue compared with normal colorectal tissue. The elevated expression of desmin in CRC tissue and different developmental stages of fetus colon was confirmed by RT-PCR and Western blot analysis. Immunohistochemical analysis showed that the elevated expression of desmin was correlated with the severity and differentiation of CRC and decreased survival rate of CRC patients. Finally by developing a highly sensitive immunoassay, desmin could be detected in human serum and was significantly elevated in CRC patients compared with healthy volunteers. We propose that desmin be considered a potential oncofetal serum tumor marker for CRC that may have significance in the detection of patients with CRC.

Highlights

  • Colorectal cancer (CRC) is the third most common cancer worldwide and has poor prognosis

  • Expressed Proteins among Colorectal Carcinoma, Normal Colorectal Tissue, and Fetal Colorectal Tissue—CRC tissues and adjacent normal colorectal tissues from 10 patients and fetal colorectal tissues from 10 induced abortion fetuses under 4 months old were analyzed in triplicate by 2-DE

  • Statistical analysis of resultant 2-D gels revealed that 42 protein spots were differentially expressed among fetal colorectal tissue, CRC, and normal colorectal tissue

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Summary

EXPERIMENTAL PROCEDURES

Specimens—Tissue specimens and blood samples were collected from the Six People’s Hospital, Shanghai Jiao Tong University in accordance with approved human subject guidelines approved by the Scientific and Ethical Committee of Shanghai Jiao Tong University. All these samples were taken by experienced surgeons and examined by experienced pathologists. 152 paraffin-embedded CRC tissue samples, 30 CRC paired adjacent normal tissues, and 36 colorectal adenoma specimens were obtained between the years 1999 and 2003. IPG strips (18 cm, pH 4 –7, non-linear; Bio-Rad) were passively rehydrated using 400 ␮l of rehydration buffer for 12 h at 17 °C.

Clinical features
Differentiation grading Well Moderate Poor Total
UICC IV
RESULTS
Peptides identifiedi
DISCUSSION
TABLE VII Relevance of the location of CRC to desmin immunoreactivity
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