Significance of PGP9.5 Expression in Cancer-Associated Fibroblasts for Prognosis of Colorectal Carcinoma

Abstract

To assess the expression of a cancer-associated fibroblasts (CAFs) marker as an indicator of prognosis, we raised anti-protein gene product 9.5 (PGP9.5) monoclonal antibody against cultured fibroblasts. PGP9.5 expression in cultured normal fibroblasts was increased by transforming growth factor beta stimulation, indicating the phenotypic alteration to activated fibroblast. We immunohistochemically evaluated PGP9.5 expression with the CAFs of 110 colorectal cancer cases under T3 stage. PGP9.5 immunoreactivity in 30% or more of CAFs was defined as high PGP9.5 expression, and the other cases were considered as having low PGP9.5 expression. Patients with high PGP9.5 expression (42.7%) had significantly shorter survival and a higher incidence of recurrence than the low PGP9.5 expression group (P = .002 and P < .001, respectively). Multivariate analysis indicated PGP9.5 expression as an independent prognostic factor for overall and recurrence-free survival partly as well as lymph node metastasis. These results indicate that PGP9.5 expression in CAFs is a helpful finding to represent the overall biologic behavior of advanced colorectal cancer.

Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy?

“…Fibroblast proliferation, angiogenesis and nerve in-growth are all important in the healing process47; this is consistent with our findings of increased vascularity and PGP9.5 expression after rotator cuff repair. The immunopositive reactions of some fibroblasts to PGP9.5 is of interest and may relate to a subpopulation of type B synoviocyte-like cells that have been repeatedly seen in the horse48; of note PGP9.5-immunopositivity has previously been demonstrated in the human fibroblasts 49. The increase in the NK-1 and TrkA receptors, seen specifically around vascular structures, points towards the importance of both substance P and NGF in the process of neurovascular ingrowth 50.…”

Differential survival trends of stage II colorectal cancer patients relate to promoter methylation status of PCDH10, SPARC, and UCHL1

“…44 Data from several in vitro studies and mouse models suggest that UCHL1 acts as an oncogene in cancer pathogenesis. [45][46][47] Furthermore, high expression of UCHL1 in cancerassociated fibroblasts was shown as an independent, negative prognostic factor for overall and recurrence-free survival. 45 Albo et al 48 reported that neurogenesis-in which UCHL1 is a key player-in colorectal cancer is involved in tumor progression and associated with poor outcome.…”

“…[45][46][47] Furthermore, high expression of UCHL1 in cancerassociated fibroblasts was shown as an independent, negative prognostic factor for overall and recurrence-free survival. 45 Albo et al 48 reported that neurogenesis-in which UCHL1 is a key player-in colorectal cancer is involved in tumor progression and associated with poor outcome. In 2008, Mizukami et al 49 proposed that hypomethylation resulting in re-expression of UCHL1 was significantly associated with lymph node metastasis in colorectal cancer.…”

microRNA-145 promotes differentiation in human urothelial carcinoma through down-regulation of syndecan-1

“…UCHL-1 is overexpressed in pancreatic endocrine tumors, as well as in colorectal and lung cancers. This enzyme is a neuroendocrine marker that recognizes and hydrolyzes a peptide bond at the C-terminus of ubiquitin, and remodels synapses by controlling ubiquitin homeostasis [31][32][33]. In the current study, miR-145 provided to suppress cell proliferation and reverse urothelial carcinomas to the pluripotent cells with stem cell features through induction of senescence, then prompted differentiation to multiple lineages such as squamous, glandular and neuroendocrine cells.…”