Dataset Information

Prognostic Significance of ?-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series.

ABSTRACT: Robust biomarkers that can precisely stratify patients according to treatment needs are in great demand. The literature is inconclusive for most reported prognostic markers for colorectal cancer (CRC). Hence, adequately reported studies in large representative series are necessary to determine their clinical potential. We investigated the prognostic value of three Wnt signaling-associated proteins, ?-catenin, E-cadherin, and SOX9, in a population-representative single-hospital series of 1290 Norwegian CRC patients by performing immunohistochemical analyses of each marker using the tissue microarray technology. Loss of membranous or cytosolic ?-catenin and loss of cytosolic E-cadherin protein expression were significantly associated with reduced 5-year survival in 903 patients who underwent major resection (722 evaluable tissue cores) independently of standard clinicopathological high-risk parameters. Pre-specified subgroup analyses demonstrated particular effect for stage IV patients for ?-catenin membrane staining (P?=?0.018; formal interaction test P?=?0.025). Among those who underwent complete resection (714 patients, 568 evaluable), 5-year time-to-recurrence analyses were performed, and stage II patients with loss of cytosolic E-cadherin were identified as an independent high-risk subgroup (P?=?0.020, formal interaction test was not significant). Nuclear ?-catenin and SOX9 protein, regardless of intracellular location, were not associated with prognosis. In conclusion, the protein expression level of membranous or cytosolic ?-catenin and E-cadherin predicts CRC patient subgroups with inferior prognosis.

SUBMITTER: Bruun J

PROVIDER: S-EPMC4033250 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Prognostic Significance of β-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series.

Bruun Jarle J Kolberg Matthias M Nesland Jahn M JM Svindland Aud A Nesbakken Arild A Lothe Ragnhild A RA

Frontiers in oncology 20140521

Robust biomarkers that can precisely stratify patients according to treatment needs are in great demand. The literature is inconclusive for most reported prognostic markers for colorectal cancer (CRC). Hence, adequately reported studies in large representative series are necessary to determine their clinical potential. We investigated the prognostic value of three Wnt signaling-associated proteins, β-catenin, E-cadherin, and SOX9, in a population-representative single-hospital series of 1290 Nor ...[more]

PMID: 24904831

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Project description:Expression levels of LI-cadherin and miR-378e in the serum of patients with colorectal cancer, and the diagnostic value and prognostic significance in colorectal cancer were investigated. A total of 110 patients who were diagnosed with colorectal cancer in Weihai Central Hospital, from January 2012 to November 2014, were selected and enrolled in the experimental group, and 90 healthy subjects who underwent physical examination were enrolled in the control group. The expression level of miR-378e in serum was detected by reverse transcription-quantitative PCR and the expression of LI-cadherin in serum was detected by ELISA. ROC curves of LI-cadherin and miR-378e were drawn and the sensitivity and specificity of the diagnosis were estimated. The association of the expression levels of LI-cadherin and miR-378e with the survival of the patients was analyzed. LI-cadherin and miR-378e expression levels were significantly higher in the control group than those in the experimental group (P<0.001). LI-cadherin was significantly associated with the pathogenic site, the lymphatic metastasis, depth of infiltration, degree of differentiation and clinical stage (P<0.05). The sensitivity and specificity of the LI-cadherin combined with miR-378e detection were respectively 86 and 94%; the sensitivity of miR-378e detection was the highest, as well as the specificity of the combined detection. At the end of the follow-up period, the survival rates of the patients in the LI-cadherin high-expression group and miR-378e high-expression group were significantly higher than those in the low-expression groups (P<0.05). There was a significant positive correlation between the LI-cadherin and miR-378e expression levels in both the experimental and control group (r=0.5845 and 0.6356, respectively; P<0.05). In conclusion, LI-cadherin and miR-378e are expressed at low levels in colorectal cancer, suggesting that they have a good diagnostic value for colorectal cancer and can be used as biomarkers for colorectal cancer prognosis.

Project description:The cadherin-catenin proteins have in common with heat shock proteins (HSP) the capacity to bind/interact proteins of other classes. Moreover, there are common molecular pathways that connect the HSP response and the cadherin-catenin protein system. In the present study, we have explored whether in breast cancer the HSP might interact functionally with the cadherin-catenin cell adhesion system. Beta-catenin was immunoprecipitated from breast cancer biopsy samples, and the protein complexes isolated in this way were probed with antibodies against HSP family members. We are thus the first to demonstrate a specific interaction between beta-catenin and Hsp27. However, beta-catenin did not bind Hsp60, Hsp70, Hsp90, gp96, or the endoplasmic reticulum stress response protein CHOP. To confirm the finding of Hsp27-beta-catenin interaction, the 27-kDa immunoprecipitated band was excised from one-dimensional polyacrylamide gel electrophoresis gels and submitted to liquid chromatography-tandem mass spectrometry with electrospray ionization, confirming a role for Hsp27. In addition, beta-catenin interacted with other proteins including heat shock transcription factor 1, P-cadherin, and caveolin-1. In human breast cancer biopsy samples, beta-catenin was coexpressed in the same tumor areas and in the same tumor cells that expressed Hsp27. However, this coexpression was strong when beta-catenin was present in the cytoplasm of the tumor cells and not when beta-catenin was expressed at the cell surface only. Furthermore, murine breast cancer cells transfected with hsp25 showed a redistribution of beta-catenin from the cell membrane to the cytoplasm. When the prognostic significance of cadherin-catenin expression was examined by immunohistochemistry in breast cancer patients (n = 215, follow-up = >10 years), we found that the disease-free survival and overall survival were significantly shorter for patients expressing P-cadherin and for patients showing expression of beta-catenin in the cytoplasm only (not at the cell surface). The interactions of beta-catenin with Hsp27 and with HSF1 may explain some of the molecular pathways that influence tumor cell survival and the clinical significance in the prognosis of the breast cancer patients.

Project description:BackgroundsHepatocellular Carcinoma (HCC) is one of the most common malignancy of liver and HCC-related morbidity and mortality remains at high level. Researchers had investigated whether and how reduced E-cadherin expression impacted the prognosis of patients with HCC but the results reported by different teams remain inconclusive.MethodsA systematic literature search was performed in all available databases to retrieve eligible studies and identify all relevant data, which could be used to evaluate the correlation between reduced E-cadherin expression and clinicopathological features and prognosis for HCC patients. A fixed or random effects model was used in this meta-analysis to calculate the pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI).ResultsTotal 2439 patients in thirty studies matched the selection criteria. Aggregation of the data suggested that reduced E-cadherin expression in HCC patients correlated with poor 1-, 3- and 5-year overall survival. The combined ORs were 0.50 (n = 13 studies, 95% CI: 0.37-0.67, Z = 4.49, P<0.00001), 0.39 (n = 13 studies, 95% CI: 0.28-0.56, Z = 5.12, P<0.00001), 0.40 (n = 11 studies, 95% CI: 0.25-0.64, Z = 3.82, P = 0.0001), respectively. Additionally, the pooled analysis denoted that reduced E-cadherin expression negatively impacts recurrence-free survival (RSF) with no significant heterogeneity. The pooled ORs for 1-, 3- and 5- year RSF affected by down-regulated E-cadherin were 0.73 (n = 6 studies, 95% CI: 0.54-1.00, Z = 1.95, P = 0.05), 0.70 (n = 6 studies, 95% CI: 0.52-0.95, Z = 2.32, P = 0.02), 0.66 (n = 5 studies, 95% CI: 0.48-0.90, Z = 2.64, P = 0.008). And what's more, reduced E-cadherin expression tended to be significantly associated with metastasis (OR = 0.31, 95% CI: 0.16-0.60, Z = 3.50, P = 0.0005), vascular invasion (OR = 0.76, 95% CI: 0.59-0.98, Z = 2.14, P = 0.03), advanced differentiation grade (OR = 0.31, 95% CI: 0.21-0.45, Z = 6.04, P<0.00001) and advanced TMN stage (T3/T4 versus T1/T2) (OR = 0.61,95% CI:0.38-0.98, Z = 2.05, P = 0.04).ConclusionsReduced E-cadherin expression indicates a poor prognosis for patients with HCC, and it may have predictive potential for prognosis of HCC patients.

Dataset Information

Prognostic Significance of ?-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series.

Publications

Prognostic Significance of β-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series.

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