Association of IRS2 overexpression with disease progression in intrahepatic cholangiocarcinoma

You,Huey‑Ling; Liu,Ting‑Ting; Weng,Shao‑Wen; Chen,Chang‑Han; Wei,Yu‑Ching; Eng,Hock‑Liew; Huang,Wan‑Ting

doi:10.3892/ol.2018.9284

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
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Affiliations: Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan, R.O.C., Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan, R.O.C., Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan, R.O.C., The Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan, R.O.C., Department of Pathology, Kaohsiung Municipal Ta‑Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan, R.O.C.
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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