RGD Reference Report - Hepatitis A virus cellular receptor 1/kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression.

General

Hepatitis A virus cellular receptor 1/kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression.
Authors:	Cuadros, T Trilla, E Vila, MR De Torres, I Vilardell, J Messaoud, NB Salcedo, M Sarro, E Lopez-Hellin, J Blanco, A Mir, C Ramon Y Cajal, S Itarte, E Morote, J Meseguer, A
Citation:	Cuadros T, etal., Eur J Cancer. 2013 May;49(8):2034-47. doi: 10.1016/j.ejca.2012.12.020. Epub 2013 Jan 23.
RGD ID:	7245470
Pubmed:	PMID:23352434 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.ejca.2012.12.020 (Journal Full-text)
AIM OF THE STUDY: To correlate hepatitis A virus cellular receptor (HAVCR)/kidney injury molecule-1 (KIM-1) expression in clear cell renal cell carcinoma (ccRCC) tumours with patient outcome and study the consequences of HAVCR/KIM-1 ectodomain shedding. METHODS: HAVCR/KIM-1 expression in ccRCC, oncocytomes, papillary carcinomas and unaffected tissue counterparts was evaluated. Minimal change disease and pre-clamping normal and ccRCC tissue biopsies were included. Tissue microarrays from 98 ccRCC tumours were analysed. Tumour registry data and patient outcome were retrospectivelly collected. Deletions in HAVCR/KIM-1 ectodomain and lentiviral infection of 786-O cells with HAVCR/KIM-1 mutated constructs to determine their subcellular distribution and invasive capacity were performed. RESULTS: HAVCR/KIM-1 was expressed in ccRCC, papillary tumours and in tubule cells of adjacent and distal unaffected counterparts of ccRCC tumours. The latest was not related to ischemic or tumour-related paracrine effects since pre-clamping normal biopsies were positive for HAVCR/KIM-1 and unaffected counterparts of papillary tumours were negative. HAVCR/KIM-1 analyses in patients and the invasive capacity of HAVCR/KIM-1 shedding mutants in cell lines demonstrated that: (i) relative low HAVCR/KIM-1 membrane levels correlate with activated shedding in ccRCC patients and mutant cell lines; (ii) augmented shedding directly correlates with higher invasiveness and tumour malignancy. CONCLUDING STATEMENTS: Constitutive expression of HAVCR/KIM-1 in kidney might constitute a susceptibility trait for ccRCC tumour development. Enhanced HAVCR/KIM-1 ectodomain shedding promotes invasive phenotype in vitro and more aggressive tumours in vivo.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
renal cell carcinoma	disease_progression	IEP		7245470		RGD
renal cell carcinoma	disease_progression	ISO	HAVCR1 (Homo sapiens)	7245470; 7245470		RGD

Objects Annotated

Genes (Rattus norvegicus)

Havcr1 (hepatitis A virus cellular receptor 1)

Genes (Mus musculus)

Havcr1 (hepatitis A virus cellular receptor 1)

Genes (Homo sapiens)

HAVCR1 (hepatitis A virus cellular receptor 1)

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Hepatitis A virus cellular receptor 1/kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression.