Dystroglycan is Associated with Tumor Progression and Patient Survival in Gastric Cancer

Abstract

Previous reports had indicated that there was a possible correlation of dystroglycan (DG) with biological behavior of cancer cells and cancer patients' survival. However, the role of DG expression in gastric cancer was rarely studied. In this study, α-DG and β-DG expression were determined by immunohistochemistry in specimens of primary cancer, metastatic lymph node, distal metastatic lesion, and their normal counterpart tissues in 20 gastric cancer patients. Correlations between α-DG and β-DG expression and prognosis were retrospectively analyzed. Our results found that positive expression of α-DG in normal mucosa, paired primary tumor, metastatic lymph node and distal metastatic site was detected in 95%, 70%, 25%, and 5% specimens, individually. Regarding β-DG,it was 70%, 55%, 10%, and 10%, individually. Patients who had lower α-DG expression in tumors than in normal counterparts showed poor survival (p = 0.002), whereas such a correlation was not found in the case of β-DG (p = 0.079). Difference of α-DG between primary tumor and its normal counterparts was an independent prognostic factor in gastric cancer with distal metastasis. This study showed DG expression was gradually reduced during tumor progression. Different expression of α-DG, but not β-DG, between primary tumor and normal specimen, correlated with patient survival, implicating a potential marker for gastric cancer prognosis.

Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

“…We and others previously reported that loss of the α subunit of the DG complex (α-DG) is a frequent event in human cancers [6,8,10,12,14-16]. We also demonstrated, by western blot analysis, that α-DG is frequently reduced in colon cancer tissues compared to normal adjacent normal tissues while the β subunit did not display significant variations between normal and tumour tissues [12].…”

Loss of LARGE2 Disrupts Functional Glycosylation of α-Dystroglycan in Prostate Cancer

“…Consistent with the idea that ␣DG hypoglycosylation is associated with a more aggressive disease phenotype, hypoglycosylation of ␣DG has, in some small retrospective studies, demonstrated potential prognostic value in predicting disease recurrence or survival (54,(57)(58)(59)(60). Prior work in prostate cancer demonstrated that ␣DG hypoglycosylation is associated with increasing Gleason score (46,47).…”

Effects and regulation of dystroglycan glycosylation in cancer

“…DG was originally shown to be significantly downregulated in breast and prostate cancer with the greatest dysregulation found in the higher-grade tumors (Henry, Cohen et al 2001). These findings have since been recapitulated in other studies in breast, colon, pancreatic, gastric, and renal adenocarcinoma (Sgambato, Migaldi et al 2003, Sgambato, Camerini et al 2007, Moon, Rha et al 2009, Jiang, Rieder et al 2011, Shen, Xu et al 2012). These findings have also been seen in squamous cell carcinomas originating from the oral cavity, cervix, and vulva , Sgambato, Caredda et al 2010.…”

“…Consistent with the idea that αDG hypoglycosylation is associated with a more aggressive disease phenotype, hypoglycosylation of αDG has, in some small retrospective studies, demonstrated potential prognostic value in predicting disease recurrence or survival (Sgambato, Camerini et al 2007, Moon, Rha et al 2009, Sgambato, Caredda et al 2010, Jiang, Rieder et al 2011, Shen, Xu et al 2012. Prior work in prostate cancer demonstrated that αDG hypoglycosylation is associated with increasing Gleason score (Sgambato, De Paola et al 2007, Shimojo, Kobayashi et al 2011).…”

“…Overall survival is inversely associated with DG staining in renal adenocarcinoma, gastric tumors, oral cancers, colon, and breast adenocarcinomas (Sgambato, Migaldi et al 2003, Sgambato, Camerini et al 2007, Moon, Rha et al 2009, Sgambato, Caredda et al 2010. One study has demonstrated that specific loss of alpha-DG immunoreactivity, but not beta-DG, inversely associates with survival and may serve as a novel biomarker for gastric carcinoma (Shen, Xu et al 2012). Correspondingly, investigation of DG as a prognostic biomarker is still being pursued by a number of laboratories.…”