[Tissue microarray (TMA) validated progression markers in colorectal cancer using antibody microarrays].
BACKGROUND
The exact molecular biological background of colorectal cancer development and progression are not hitherto known. Using microarray systems, hundreds or thousands of parameters could be examined simultaneously for answering the mentioned questions.


OBJECTIVE
To identify possible protein markers of colorectal cancer development and progression using antibody array, and the validation of these markers on tissue microarrays done with colorectal cancer samples. Furthermore, to determine colorectal cancer diagnostic marker combination in protein level.


METHODS
Surgically resected samples from ten Dukes B and six Dukes D stage patients containing both diseased and un-involved parts of the colon were freshly frozen. The samples were homogenized and the extracted proteins were used for Clontech AB500 arrays. Twelve selected genes were validated on tissue microarrays.


RESULTS
The expression of 67 proteins was altered (p < 0.05) between the normal colon and cancerous samples. These genes are related to apoptosis (n = 5), cell cycle regulation (n = 7), transcription (n = 4), DNA replication (n = 6) and other cell functions, such as transport and cell adhesion (n = 45). Twelve potential markers were immunohistochemically validated on morphological level by using tissue microarrays (CYCA1, HSP60, TOP1, APC, CBP, ERK, EGFR, C-myc, Cald, DARPP32, MRE11A, AR, EPS8).


CONCLUSIONS
Based on these results, validated colorectal cancer development related protein markers are involved in a wide spectrum of cell functions such as apoptosis, cell cycle regulation, and signal transduction. A set of six proteins has been determined, which helps to differentiate between normal specimen, early and late stage colorectal cancer with high sensitivity and specificity.
Spisák
Sándor
S
Semmelweis Egyetem, Altalános Orvostudományi Kar, II. Belgyógyászati Klinika, Budapest. spisak@abc.hu
Galamb
Barnabás
B
Wichmann
Barnabás
B
Sipos
Ferenc
F
Galamb
Orsolya
O
Solymosi
Norbert
N
Nemes
Balázs
B
Tulassay
Zsolt
Z
Molnár
Béla
B
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D015203:Reproducibility of Results
D014408:Biomarkers, Tumor