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.