Molecular and immunologic markers of kidney cancer-potential applications in predictive, preventive and personalized medicine.
Kidney cancer is one of the deadliest malignancies due to frequent late diagnosis (33 % or renal cell carcinoma are metastatic at diagnosis) and poor treatment options. There are two major subtypes of kidney cancer: renal cell carcinoma (RCC) and renal pelvis carcinoma. The risk factors for RCC, accounting for more than 90 % of all kidney cancers, are smoking, obesity, hypertension, misuse of pain medication, and some genetic diseases. The most common molecular markers of kidney cancer include mutations and epigenetic inactivation of von Hippel-Lindau (VHL) gene, genes of vascular endothelial growth factor (VEGF) pathway, and carbonic anhydrase IX (CIAX). The role of epigenetic pathways, including DNA methylation and chromatin structure remodeling, was also demonstrated. Immunologic properties of RCC enable this type of tumor to escape immune response effectively. An important role in this process is played by tumor-associated macrophages that demonstrate mixed M1/M2 phenotype. In this review, we discuss molecular and cellular aspects for RCC development and current state of knowledge allowing personalized approaches for diagnostics and prognostic prediction of this disease. A set of macrophage markers is suggested for the analysis of the association of macrophage phenotype and disease prognosis.
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany.
Amanda
A
Mickley
Blokhin Cancer Research Center, Moscow, Russia.
Olga
O
Kovaleva
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany ; Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany ; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia.
Julia
J
Kzhyshkowska
Blokhin Cancer Research Center, Moscow, Russia ; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia ; Laboratory of the Tumour Stromal Cells Biology, Institute of Carcinogenesis, Blokhin Cancer Research Center, Kashirskoye Shosse 24, Moscow, Russia.
Alexei
A
Gratchev
Biomarker panel; Disease prognosis; Epigenetics; Immune response; Kidney; Metastatic disease; Molecular target; Mutation; Predictive, preventive and personalized medicine; Renal cell carcinoma; Tumor-associated macrophage