Colorectal surgery, open abdominal surgery, and smoking history were found to be independent predictive factors for PPOI in patients who underwent major abdominal surgery. A nomogram based on these factors was shown to be useful for identifying patients with a high probability of developing PPOI.
We found matrilysin expression in primary melanomas and in metastatic melanomas. We further demonstrated that the matrilysin IHC staining score was associated with invasive depth of primary melanoma lesions and metastases. Our observations indicate that matrilysin may be associated with melanoma progression, and may enhance melanoma tumour cell invasion. Therefore, matrilysin may be potentially valuable as a prognostic indicator to predict the clinical behaviour of melanoma.
Background & Aims
LGR5 enhances Wnt‐β‐catenin signalling; however, involvement of LGR5 or Wnt‐β‐catenin signalling in ICC progression has not been reported.
Methods
Functions and regulations of LGR5‐mediated β‐catenin activation in ICC progression were evaluated using surgical specimens collected from 61 ICC patients or 2 ICC cell lines.
Results
LGR5 expression was increased in some cases of ICC. It was positively correlated with β‐catenin activation, OLFM4 expression and STAT3 activation, and negatively correlated with GRIM19 expression in ICC, thereby enhancing cancer stem cell (CSC)‐like property and EMT. High LGR5 expression was an independent factor for poor prognosis in ICC after operation. In vitro, Wnt inhibition by IWP‐2 suppressed β‐catenin activation, OLFM4 expression and STAT3 activation. IWP‐2 treatment decreased expression of EpCAM, CD133, vimentin and increased E‐cadherin expression. The rate of mesenchymal cells was decreased and cell invasiveness was suppressed after IWP‐2 treatment, suggesting that Wnt‐β‐catenin signalling enhanced CSC‐like property and EMT by activating STAT3. In addition, LGR5 knockdown inhibited β‐catenin activation, resulting in suppression of β‐catenin‐induced STAT3 activation through inhibition of OLFM4‐GRIM19 cascade. As these results, LGR5 knockdown suppressed CSC‐like property and EMT. Therefore, LGR5 was a key regulator for β‐catenin activation, and β‐catenin was unable to be activated without LGR5.
Conclusions
LGR5 is essential for β‐catenin activation induced by Wnt signalling. Activated β‐catenin further activates STAT3 and enhances CSC‐like property and EMT, leading to aggressive tumour progression and poor prognosis in patients with ICC. Therefore, LGR5 is an excellent prognostic predictor and a promising therapeutic target for ICC.
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