Identification of
biomarkers could lead to the development of effective screening tests for
colorectal cancer. A previous study from our laboratory showed specific alterations of nuclear structure in
colon cancer. In an effort to characterize these
biomarkers,
protein spots were selected from separations made by two-dimensional gel electrophoresis, which were analyzed by mass spectrometry. The sequences obtained from the isolated spots revealed that they have close similarity to
creatine kinase B (CKB)
isoforms,
heterogeneous nuclear ribonucleoprotein F (
hnRNP F) and high mobility group box 1
protein (
HMGB1)
isoforms. To determine the expression of these
proteins in
colon cancer, expression was studied in 9
tumor and matched adjacent normal pairs, 5 donor colons, 16
polyps, 4 metastatic liver lesions and matched adjacent normal pairs, and 3 liver donors. CKB and
hnRNP F were expressed in 78% and 89% of colon
tumors, respectively.
hnRNP F had a higher frequency of expression than CKB in premalignant
polyps. With the establishment of differential expression of the
proteins in
colon cancer, their subcellular localization was analyzed. The subcellular fractions studied both showed high
protein levels of
hnRNP F in colon
tumors compared with normal colon tissues. Surprisingly, subcellular levels of CKB were decreased in colon
tumors, suggesting that the observed high CKB levels in nuclear matrix extracts are caused by the enhanced localization of CKB to the nuclear matrix during colon
tumorigenesis. These results suggest an involvement of
hnRNP F and CKB in
colorectal cancer. Additionally, they suggest that
hnRNP F is a potential marker for
colorectal cancer progression.