UC San Diego

The primate SIGLEC12 gene encodes one of the CD33-related Siglec family of signaling molecules in immune cells. Siglecs are normally expressed on hematopoietic cells. Interestingly, it was previously reported that the human SIGLEC12 gene product Siglec-XII is expressed on some epithelium and also on prostate carcinomas. Stably transfected Siglec-XII-expressing prostate cancer cells demonstrated altered regulation of several genes associated with carcinoma progression, as well as enhanced growth in nude mice. However, SIGLEC12 allele status did not predict prostate carcinoma incidence. Here, we confirm and expand on previous immunohistochemical analysis of Siglec-XII expression in human epithelium, and found that Siglec-XII expression correlates with an increased risk of late stage carcinoma development. While no significant correlation was found between Siglec-XII expression and incidence of early stage or slow progressing cancers in two patient cohorts, we found that Siglec-XII expression is correlated with a significantly increased rate of late stage carcinoma progression in a late stage colorectal carcinoma patient cohort. We also found through RNA-Seq analysis that several genes associated with cancer progression are differentially expressed in a stably transfected PC-3 Siglec-XII expressing cell line. Finally, we propose a unique new noninvasive test, a dot blot using urine samples which may become a screening test for the efficient determination of an individual’s Siglec-XII status. This test may thus become useful as a diagnostic screen in the future. Thus, polymorphic expression of Siglec-XII in humans may determine progression of certain late stage carcinomas.