A Decreased Ratio of Laminin-332 β3 to γ2 Subunit mRNA is Associated with Poor Prognosis in Colon Cancer

Laminin-332 (Ln-332) is a heterotrimeric glycoprotein (alpha 3 beta 3 gamma 2) unique to epithelial cells with crucial roles in signaling, adhesion, and migration. Altered localization or expression levels of Ln-332, particularly its gamma 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 gamma 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 early- and 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 beta 3:gamma 2 mRNA ratio between normal (n = 10) and early-stage colon cancer (n = 29) specimens. The beta 3:gamma 2 ratio was further decreased in metastatic colon cancer (n = 41) compared with early-stage samples. Our findings raise the possibility that Ln-332 gamma 2 may be a therapeutic target against metastatic colon cancer because a lowered beta 3:gamma 2 ratio would reduce expression of heterotrimeric Ln-332 and increase monomeric gamma 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)