Searching for Hif1-α interacting proteins in renal cell carcinoma

Kidney tumours are frequently characterised by hypoxic conditions due to a local imbalance between oxygen (O-2) supply and consumption. Hif1-alpha regulates angiogenesis, tumour growth, tumour progression, metastatic spread, and glucose metabolism by acting as a transcription factor for relevant genes. Here, we describe an immunohistochemical study of Hif1-alpha, a comprehensive computational study of Hif1-alpha interacting proteins (HIPs), an analysis correlating expression levels of Hif1-alpha with upstream and downstream proteins, and an analysis of the utility of Hif1-alpha for prognosis in a cohort of patients with renal cell carcinoma. The patient cohort included 80 patients. For immunohistochemistry evaluation, tissue microarrays were constructed. The IntAct, MINT, and BOND databases were used for the HIP approach. The Kruskal-Wallis test was used for comparing protein expression with pathology measurements. Correlation was expressed as the Pearson coefficient. Hif1-alpha expression correlates significantly with the clear histological subtype of renal cell carcinoma (p < 0.01). The samples with the worst prognoses related to the pathological variables analysed showed the highest levels of Hif1-alpha expression. Significant correlations were found with Bcl-2, CAIX, C-kit, EGFR, TGF-beta, proteins of the VEGF family, proteins related to differentiation (such as Notch1 and Notch3) and certain metabolic enzymes. Bioinformatic analysis suggested 45 evidence-based HIPs and 4 complexes involving protein Hif1-alpha. This work summarises the multifaceted role of Hif1-alpha in the pathology of renal cell carcinomas, and it identifies HIPs that could help provide mechanistic explanations for the different behaviours seen in tumours.