Two-dimensional electrophoretic analysis of cytoplasmic polypeptides expressed by normal and cancerous colon tissues

To analyse the cytoplasmic polypeptides from malignant and nonmalignant tissues of the large intestine and investigate their relationship to colon cancer.

The investigation was carried out in 64 large intestinal tissues coming from 32 individuals, using high-resolution 2-dimensional (2D) electrophoresis (2D-PAGE). Thirty specimens were diagnosed as primary adenocarcinomas and 2 were nonmalignant. The other 32 specimens represented mirror biopsies from the respective patient obtained far from the tumor area.

Pathological and nonpathological protein maps from the same patient highlighted several differences associated with malignancy, over and above natural complexity. Polypeptide overexpression was observed in adenocarcinomas, however in poorly differentiated tissues a decline in number and density of protein spots was observed in an area of isoelectric point (PI) between pH 6.3-7.2 and molecular weight (MW) 17.5-24 kDa. Three polypeptides, Pa (51/4.2), Pb (30/6.1) and Pc (21/7.3), were not detected in normal tissues and 27 polypeptides showed significantly increased densities in adenocarcinomas.

Pa and Pb polypeptides show significantly increased densities in premature stages of the disease, and Pc provides a promising monitoring tool for the progress of metastases. The low prevalence of the above mentioned polypeptides in tissues from mirror biopsies raises questions as to the extent of the disease far from the tumor area. Also, the quantitative differences are associated with the appearance and development of the disease. We believe that these findings are important, highlighting the complexity and scope for further research in the diagnosis, monitoring and potential therapy of human colon cancer.