Association of IRS2 overexpression with disease progression in intrahepatic cholangiocarcinoma

  • Authors:
    • Huey‑Ling You
    • Ting‑Ting Liu
    • Shao‑Wen Weng
    • Chang‑Han Chen
    • Yu‑Ching Wei
    • Hock‑Liew Eng
    • Wan‑Ting Huang
  • View Affiliations

  • Published online on: August 8, 2018     https://doi.org/10.3892/ol.2018.9284
  • Pages: 5505-5511
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Abstract

Insulin receptor substrate 2 (IRS2) is a candidate driver oncogene frequently amplified in cancer and is positively associated with IRS2 expression. The overexpression of IRS2 has been suggested to promote tumor metastasis. However, its function in intrahepatic cholangiocarcinoma (iCCA) has not been investigated extensively. The present study examined 86 cases of iCCA to analyze IRS2 expression and its correlation with clinicopathological characteristics using immunohistochemical assays. Three stable cell lines overexpressing IRS2 were established. The mobility potential of cells was compared in the basal condition and following manipulation using cell migration and invasion assays. Epithelial‑mesenchymal transition (EMT)‑associated proteins were assessed by western blotting. IRS2 was overexpressed in 29 iCCA cases (33.7%) and was significantly more frequent in cases with large tumor size (P=0.033), classified as an advanced stage by the American Joint Committee on Cancer (P=0.046). In comparison with the control cells, the three IRS2‑overexpressing iCCA cell lines exhibited a statistically significant increase in mobility potential. Expression analysis of EMT markers demonstrated decreased epithelial marker levels and increased mesenchymal marker levels in IRS2‑overexpressing cells compared with their corresponding control cells. The results of the present study indicate that IRS2 overexpression is characterized by a large tumor size and advanced tumor stage in iCCA, and that it may increase tumor mobility potential by regulating EMT pathways. Therefore, it is a valuable predictive indicator of metastasis and may provide a novel direction for targeted therapy in iCCA.
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October-2018
Volume 16 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
You HL, Liu TT, Weng SW, Chen CH, Wei YC, Eng HL and Huang WT: Association of IRS2 overexpression with disease progression in intrahepatic cholangiocarcinoma. Oncol Lett 16: 5505-5511, 2018.
APA
You, H., Liu, T., Weng, S., Chen, C., Wei, Y., Eng, H., & Huang, W. (2018). Association of IRS2 overexpression with disease progression in intrahepatic cholangiocarcinoma. Oncology Letters, 16, 5505-5511. https://doi.org/10.3892/ol.2018.9284
MLA
You, H., Liu, T., Weng, S., Chen, C., Wei, Y., Eng, H., Huang, W."Association of IRS2 overexpression with disease progression in intrahepatic cholangiocarcinoma". Oncology Letters 16.4 (2018): 5505-5511.
Chicago
You, H., Liu, T., Weng, S., Chen, C., Wei, Y., Eng, H., Huang, W."Association of IRS2 overexpression with disease progression in intrahepatic cholangiocarcinoma". Oncology Letters 16, no. 4 (2018): 5505-5511. https://doi.org/10.3892/ol.2018.9284