Prognostic Significance of β-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, β-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 β-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 β-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 β-catenin and SOX9 protein, regardless of intracellular location, were not associated with prognosis. In conclusion, the protein expression level of membranous or cytosolic β-catenin and E-cadherin predicts CRC patient subgroups with inferior prognosis.

MicroRNA‑216b regulated proliferation and invasion of non‑small cell lung cancer by targeting SOX9

“…SOX9 has been reported to be highly expressed in a number of types of human cancer, such as prostate (36), breast (37) and colorectal (38) cancer. In NSCLC, SOX9 was upregulated at mRNA and protein levels, and the expression levels were associated with the histological stage of NSCLC and patients with a high SOX9 level exhibited a shorter survival rate.…”

Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy

“…Study cohort 1 is a population‐representative consecutive series of CRC patients from Oslo University Hospital Aker, and has been previously reported 16, 17, 18. Briefly, all patients with CRC from 1993 to 2003 were registered and clinical data were prospectively recorded.…”

“…Briefly, all patients with CRC from 1993 to 2003 were registered and clinical data were prospectively recorded. Of the 1290 patients included, 929 underwent a major resection and had tumor samples available for tissue microarray (TMA) construction 17. Colon cancer patients ≤75 years of age and all rectal cancer patients who underwent curative surgery entered a 5‐year follow‐up program as described previously 18.…”

“…The construction of TMAs has been described previously 17, 20. Sections from the TMAs were immunostained using the Dako EnVision Flex+ detections system (Dako, Glostrup, Denmark) as described previously 21.…”

Notch and Wnt signaling pathway in cancer: Crucial role and potential therapeutic targets (Review)

“…Voorham et al (120) reported observation of methylated Wnt pathway antagonists from clinical specimens. It is possible that the Wnt signaling pathway could also be used as a potential diagnostic and prognostic biomarker in CRC patients (119,121). Thus, both experimental and clinical data showed that the over activation of the Wnt signaling pathway may be a potential target for CRC.…”