Staff Scientist Yosuke Tanaka, Trainee Jun Takahashi, Research Fellow (Director) Hiroyuki Mano, and their colleagues at the National Cancer Center Research Institute have collaborated with the University of Tokyo Hospital to elucidate the molecular mechanism of kidney cancer that develops specifically in patients undergoing hemodialysis. Their findings were published in Cancer Discovery.
When chronic kidney disease progresses to end-stage renal disease, hemodialysis treatment becomes necessary. However, long-term dialysis leads to the formation of multiple cysts in the kidneys (acquired cystic kidney disease), and it is known that the subsequent risk of developing kidney cancer increases to 15 times that of the general population. Mano stated, "While this was clinically known, the question of why cyst formation leads to kidney cancer-the molecular mechanism-remained unclear."
Using spatial multiomic analyses, the research group revealed that acquired cystic kidney disease and the kidney cancer arising from it originate from proximal tubular cells, a component of the kidney. In particular, they elucidated that while long-term dialysis damages and atrophies much of the kidney tissue, there is a process by which some proximal tubules activate MET tyrosine kinase through HGF (hepatocyte growth factor) secreted from the surrounding microenvironment and then proliferate clonally while accumulating genetic mutations, forming cysts and ultimately progressing to kidney cancer. Furthermore, they found that dialysis-specific kidney cancer differs significantly in its molecular profile, including genetic abnormalities, from general kidney cancer, suggesting a carcinogenic pathway unique to dialysis kidneys.
Tanaka commented: "After about 10 years of dialysis, cysts develop in many patients, and several percent of these cases lead to kidney cancer. The carcinogenic mechanism revealed in this study may lead to risk stratification using molecular markers for kidney cancer development in dialysis patients, as well as applications for non-invasive screening using blood and urine samples."
Journal Information
Publication: Cancer Discovery
Title: Spatial Multiomic Analyses Reveal Carcinogenic Pathways in End-Stage Renal Disease
DOI: 10.1158/2159-8290.CD-25-0472
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