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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
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Karyopherin Alpha 2 Is an Adverse Prognostic Factor in Clear-Cell and Papillary Renal-Cell Carcinoma
Tim Müller1, Yuri Tolkach1, David Stahl1
1Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Background:
Karyopherin α2 (KPNA2) is involved in the nucleocytoplasmic transport system and is functionally involved in the pathogenesis of various solid tumors by the translocation of cancer associated cargo proteins. However, the role of KPNA2 in renal-cell carcinoma (RCC) is still unknown. The aim of the present study was to investigate the protein expression of KPNA2 in cancerous and healthy renal tissues to evaluate its prognostic value in RCC.
Patients And Methods:
We assessed KPNA2 protein expression via immunohistochemistry in a well-characterized cohort of 240 RCC patients by using a quantitative image analysis software. In addition, we analyzed publicly available gene expression data from The Cancer Genome Atlas (TCGA).
Results:
A subgroup of clear-cell RCC (ccRCC) showed elevated protein expression levels of KPNA2. Most remarkably, we detected a correlation between high KPNA2 protein expression and shorter overall survival times as well as higher tumor stage and International Society of Urologic Pathology grade in ccRCC. However, the prognostic value of KPNA2 was not confirmed by multivariate Cox regression analysis when tested together with strong prognostic factors like tumor stage, lymph node metastasis, International Society of Urologic Pathology grade, and resection status. The results of the TCGA gene expression data analysis confirmed the prognostic value of KPNA2 in ccRCC. Additionally, KPNA2 expression was identified as an adverse factor in papillary RCC at the transcript level.
Conclusion:
KPNA2 appears to be involved in the carcinogenesis of RCC and functions as a novel prognostic indicator.
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