A Decreased Ratio of Laminin-332 B3 to ;2 Subunit mRNA is Associated with Poor Prognosis in Colon Cancer

Laminin-332 (Ln-332) is a heterotrimeric glycoprotein (A3B3;2) unique to epithelial cells with crucial roles in signaling, adhesion, and migration. Altered localization or expression levels of Ln-332, particularly its ;2 subunit, are of prognostic value in a variety of cancers. However, the lack of standardized methodology and the limited quantification of previous study results have left unanswered questions, including the role of ;2 transcript variants and whether differential expression of this chain represents dysregulation of the whole heterotrimer. Herein, we test the hypothesis that mRNA changes in one or more Ln-332 encoding genes can be used to distinguish between earlyand advanced-stage cancer specimens and shed light on mechanistic questions raised by previous studies. Statistical analyses of human microarray data from the publicly available expression project in Oncology (expO) dataset, including examination of the distributions of Ln-332 subunit mRNA levels, identified a significant decrease in the Ln-332 B3:;2 mRNA ratio between normal (n = 10) and early-stage colon cancer (n = 29) specimens. The B3:;2 ratio was further decreased in metastatic colon cancer (n = 41) compared with early-stage samples. Our findings raise the possibility that Ln-332 ;2 may be a therapeutic target against metastatic colon cancer because a lowered B3:;2 ratio would reduce expression of heterotrimeric Ln-332 and increase monomeric ;2 secretion. Further, standardized, quantitative methods for patient prognosis and therapeutic choice could be developed based upon the Ln-332 mRNA changes we uncovered. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1584–90)