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Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

Identification and validation of NFIA as a novel prognostic marker in renal cell carcinoma

Author

  • Roger de Alwis
  • Sarah Schoch
  • Mazharul Islam
  • Christina Möller
  • Börje Ljungberg
  • Håkan Axelson

Summary, in English

Prognostic tools are an essential component of the clinical management of patients with renal cell carcinoma (RCC). Although tumour stage and grade can provide important information, they fail to consider patient- and tumour-specific biology. In this study, we set out to find a novel molecular marker of RCC by using hepatocyte nuclear factor 4A (HNF4A), a transcription factor implicated in RCC progression and malignancy, as a blueprint. Through transcriptomic analyses, we show that the nuclear factor I A (NFIA)-driven transcription network is active in primary RCC and that higher levels of NFIA confer a survival benefit. We validate our findings using immunohistochemical staining and analysis of a 363-patient tissue microarray (TMA), showing for the first time that NFIA can independently predict poor cancer-specific survival in clear cell RCC (ccRCC) patients (hazard ratio = 0.46, 95% CI = 0.24-0.85, p value = 0.014). Furthermore, we confirm the association of HNF4A with higher grades and stages in ccRCC in our TMA cohort. We present novel data that show HNF4A protein expression does not confer favourable prognosis in papillary RCC, confirming our survival analysis with publicly available HNF4A RNA expression data. Further work is required to elucidate the functional role of NFIA in RCC as well as the testing of these markers on patient material from diverse multi-centre cohorts, to establish their value for the prognostication of RCC.

Department/s

  • LUCC: Lund University Cancer Centre
  • Kidney cancer research group
  • Division of Translational Cancer Research
  • Department of Laboratory Medicine

Publishing year

2023-03-22

Language

English

Pages

261-272

Publication/Series

The Journal of Pathology: Clinical Research

Volume

9

Issue

4

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Kidney cancer research group

ISBN/ISSN/Other

  • ISSN: 2056-4538