Identification of biomarkers to improve diagnostic sensitivity of sporadic colorectal cancer in patients with low preoperative serum carcinoembryonic antigen by clinical proteomic analysis.

Background: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Carcinoembryonic antigen (CEA) assays usually give false negative results. To improve the diagnosis of primary sporadic CRC, there is an urgent need to identify new biomarkers.

Methods: We used laser pressure catapulting and proteomics to analyze overexpressed cancer associated proteins from 48 sporadic CRC patients with low preoperative serum CEA (LPSC) (<5 ng/ml). Real-time Q-PCR was used to identify the target gene transcripts. Immunoblots were carried out to validate the biomarkers.

Results: Alpha-enolase, HSP27 and macrophage migration inhibitory factor (MIF) were overexpressed in all tumor tissues from 48 LPSC CRC patients, as assessed by 2DE image analysis. The genes were also overexpressed at the transcript level in all tumor tissues from the same patients. In the immunoblot assay, only serum levels of Alpha-enolase and MIF were significantly overexpressed in the LPSC group compared to the mean levels in the control group. Combined with the determinations of preoperative CEA levels, screening for serum Alpha-enolase and MIF were shown to improve the diagnosis of primary CRC.

Conclusions: Serum Alpha-enolase and MIF may be potential biomarkers that can be used to improve clinical predication of primary CRC with LPSC.