Immunoprofiles of 11 biomarkers using tissue microarrays identify prognostic subgroups in colorectal cancer.

Abstract

BACKGROUND AND AIMS:

Genomewide expression profiling has identified a number of genes expressed at higher levels in colorectal cancer (CRC) than in normal tissues. Our objectives in this study were: 1) to test whether genes were also distinct on the protein level; 2) to evaluate these biomarkers in a series of well-characterized CRCs; and 3) to apply hierarchical cluster analysis to the immunohistochemical data.

METHODS:

Tissue microarrays (TMAs) comprising 351 CRC specimens from 270 patients were constructed to evaluate the genes Adam10, Cyclin D1, Annexin II, NFKB, Casein kinase 2 beta (CK2B), YB-1, P32, Rad51, c-fos, IGFBP4, and Connexin26 (Cx26). In total, 3,797 samples were analyzed.

RESULTS:

Unsupervised hierarchical clustering discovered subgroups of CRC that differed by tumor stage and survival. Kaplan-Meier analysis showed that reduced Cx26 expression was significantly associated with shorter patient survival and higher tumor grade (G1/G2 vs G3, P = .02), and Adam10 expression with a higher tumor stage (pT1/2 vs pT3/4, P = .04).

CONCLUSIONS:

Our study highlights the potential of TMAs for a higher-dimensional analysis by evaluating serial sections of the same tissue core (three-dimensional TMA analysis). In addition, it endorses the use of immunohistochemistry supplemented by hierarchical clustering for the identification of tumor subgroups with diagnostic and prognostic signatures.

• Authors: Thomas Knösel, Anna Emde, Karsten Schlüns, Yuan Chen, Karsten Jürchott, Matthias Krause, Manfred Dietel, Iver Petersen
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 7 Issue 8 Pg. 741-7 (Aug 2005) ISSN: 1522-8002 [Print] United States
• PMID: 16207476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Connexins
• GJB2 protein, human
• Connexin 26

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Cluster Analysis
• Colorectal Neoplasms (genetics, metabolism)
• Connexin 26
• Connexins
• Gene Expression Profiling
• Humans
• Immunohistochemistry
• Intestinal Mucosa (metabolism)
• Prognosis
• Survival Analysis
• Tissue Array Analysis