A decreased ratio of laminin-332 beta3 to gamma2 subunit mRNA is associated with poor prognosis in colon cancer.
Laminin-332 (Ln-332) is a heterotrimeric glycoprotein (alpha3beta3gamma2) unique to epithelial cells with crucial roles in signaling, adhesion, and migration. Altered localization or expression levels of Ln-332, particularly its gamma2 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 gamma2 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 beta3:gamma2 mRNA ratio between normal (n = 10) and early-stage colon cancer (n = 29) specimens. The beta3:gamma2 ratio was further decreased in metastatic colon cancer (n = 41) compared with early-stage samples. Our findings raise the possibility that Ln-332 gamma2 may be a therapeutic target against metastatic colon cancer because a lowered beta3:gamma2 ratio would reduce expression of heterotrimeric Ln-332 and increase monomeric gamma2 secretion. Further, standardized, quantitative methods for patient prognosis and therapeutic choice could be developed based upon the Ln-332 mRNA changes we uncovered.
Guess
Cherise M
CM
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232-6840, USA.
Lafleur
Bonnie J
BJ
Weidow
Brandy L
BL
Quaranta
Vito
V
D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D000097794:Kalinin
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D000097794:Kalinin