Loss of the CBX7 protein expression correlates with a more aggressive phenotype in pancreatic cancer

Abstract

Polycomb group (PcG) proteins function as multiprotein complexes and are part of a gene regulatory mechanism that determines cell fate during normal and pathogenic development. Several studies have implicated the deregulation of different PcG proteins in neoplastic progression. Pancreatic ductal adenocarcinoma is an aggressive neoplasm that follows a multistep model of progression through precursor lesions called pancreatic intraepithelial neoplasia (PanIN). Aim of this study was to investigate the role of PcG protein CBX7 in pancreatic carcinogenesis and to evaluate its possible diagnostic and prognostic significance. We analysed by immunohistochemistry the expression of CBX7 in 210 ductal pancreatic adenocarcinomas from resection specimens, combined on a tissue microarray (TMA) including additional 40 PanIN cases and 40 normal controls. The results were evaluated by using receiver operating characteristic (ROC) curve analysis for the selection of cut-off scores and correlated to the clinicopathological parameters of the tumours and the outcome of the patients. Expression of E-cadherin, a protein positively regulated by CBX7, was also assessed. A significantly differential, and progressively decreasing CBX7 protein expression was found between normal pancreatic tissue, PanINs and invasive ductal adenocarcinoma. Loss of CBX7 expression was associated with increasing malignancy grade in pancreatic adenocarcinoma, whereas the maintenance of CBX7 expression showed a trend toward a longer survival. Moreover, loss of E-cadherin expression was associated with loss of CBX7 and with a trend towards worse patient survival. These results suggest that CBX7 plays a role in pancreatic carcinogenesis and that its loss of expression correlates to a more aggressive phenotype.

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16INK4a

“…Much less is known about how the function and expression of the PRCs and their components are controlled. The regulation of CBX7 is particularly interesting because CBX7 is implicated in senescence (Gil et al ., 2004) and cancer (Bernard et al ., 2005; Scott et al ., 2007; Pallante et al ., 2008; Karamitopoulou et al ., 2010). In addition, CBX7 levels and consequently the composition of PRC1 complexes change dramatically during ES cell differentiation (Morey et al ., 2012; O'Loghlen et al ., 2012).…”

Expression of ANRIL–Polycomb Complexes–CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value

“…Conversely, in our series of breast tumors, we showed marked CBX7 underexpression and a nonexpected high positive link between ANRIL overexpression and CDKN2A/CDKNB/ARF overexpression, and more particularly with p14/ARF. Although these results seem to be contradictory, it can be hypothesized that CBX7 can exhibit both oncosuppressive and oncogenic functions, depending on type of cancer, microenvironment, and presence of interacting proteins (32)(33)(34)(35). CBX7 underexpression was strongly correlated with high SBR histologic grade, negative ERa and PR status, and EMT and breast cancer stem cell markers.…”

CBX7 inhibits breast tumorigenicity through DKK‐1‐mediated suppression of the Wnt/β‐catenin pathway

“…CBX7-knockout mice showed the development of lung and liver tumors accompanied by cyclin E up-regulation (4). Furthermore, some clinicopathologic studies have shown that CBX7 expression is inversely associated with the development of several human cancers, including bladder, pancreatic, and colon carcinomas (13)(14)(15). A recent study also implied a negative correlation between CBX7 expression and a malignant phenotype in human breast cancer (16).…”

“…In contrast, loss of CBX7 has been associated with increasing the malignancy grade in bladder, pancreatic, breast, gastric, and colon carcinomas (13)(14)(15)(16)(17), but its tumor suppression mechanism is unclear.…”