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Identification of Nuclear Matrix Protein Alterations Associated with Human Colon Cancer¹

Departments of Urology [B. N. V., R. H. G.], Division of Gastroenterology, Department of Medicine [G. B., A. J. B., R. E. S.], University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232

The early diagnosis of colorectal cancer and the early detection of recurrence are central to effective treatment, as prognosis is directly related to the stage of the disease. When colorectal cancer is diagnosed at an early, localized stage, 5-year survival is 90%. With regional lymph node metastases, survival drops to 45–60%, and with distant metastases, 5-year survival is <5%. Development of tumor markers that can detect colon cancer at an early stage should have a major impact in mortality from this disease. The nuclear matrix is the structural scaffolding of the nucleus, and specific nuclear matrix proteins (NMPs) have been identified as an oncological "fingerprint" for bladder, renal, and prostate cancers. We have successfully used this approach to develop an immunoassay that detected bladder cancer early in a clinical trial with a sensitivity of 96.4% and a specificity of 100%. The objective of the present study was to identify the existence of a specific NMP fingerprint for human colon cancer, using high-resolution, two-dimensional gel electrophoresis, and thereby identify unique human colon cancer NMPs. Ten matched colon cancer and adjacent normal samples and 4 normal donor samples were analyzed. Analysis of multiple gels for each sample identified four proteins present in all tumor samples that were not present in the matched normal adjacent and normal colon tissue and six proteins present only in normal adjacent and normal colon tissue. Additionally, two proteins were found in all cancer and normal tissues, but not in the normal adjacent tissue. Data provided here demonstrate that examination of the nuclear matrix composition allows differentiation of colon cancer tissue from normal adjacent and normal colon tissue. Development of an assay to detect these specific NMPs by examining tissue, serum, and stool specimens is a promising modality for early detection of colorectal cancer. In addition, the functional characterization of these proteins and their early detection through the generation of NMP antibodies could significantly impact on the understanding of cancer progression and its diagnosis.

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