title: Predictive Immunohistochemical Markers Related to Drug Selection for Patients Treated with Sunitinib or Sorafenib for Metastatic Renal Cell Cancer.
abstract: Targeted drug decisions in metastatic renal cell carcinoma are exclusively made on the basis of clinical criteria. We investigated whether these biomarkers (HIF-1α, HIF-2α, CAIX, VEGF, VEGFR1, VEGFR2, VEGFR3, PDGFB, PDGFRA, PDGFRB, CD31, CD44, bcl-xL, KIT, p21, CXCR4, PTEN, (CSF)-1R, RET, and FLT-3) can predictive the different effects between sunitinib and sorafenib treatments and are available to guide targeted drug selection. We enrolled all patients who underwent nephrectomy with postoperative sunitinib- or sorafenib-treatment at our institution from 2007 to 2012. Immunohistochemical approach was applied to assess the potential differential effects of immunostainings between sunitinib- and sorafenib-treated groups. We found that patients with high HIF-2α, CD31 expression showed greater relative PFS and OS benefit and patients with high CAIX expression presented greater relative OS benefit from sunitinib than from sorafenib, patients with high VEGFR1 or PDGFRB expression levels exhibited worse relative PFS benefit from sunitinib than from sorafenib. Namely high HIF-2α, CD31, and CAIX expression levels along with low VEGFR1 and PDGFRB expression levels improved the benefit of sunitinib treatment compared with sorafenib treatment. These results can identify whether patients can benefit more from sunitinib or sorafenib for drug selection guidance, eventually with precision medicine.
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Hongzhao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Kan
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Chaofei
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Dianjun
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pathology, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D000071231:Carbonic Anhydrase IX / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D000077157:Sorafenib; D000077210:Sunitinib; D046888:Tissue Array Analysis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D000071231:Carbonic Anhydrase IX; D007211:Indoles; D009536:Niacinamide; D010671:Phenylurea Compounds; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011758:Pyrroles; D020797:Receptor, Platelet-Derived Growth Factor beta; D000077157:Sorafenib; D000077210:Sunitinib; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099162:Endothelial PAS Domain-Containing Protein 1; C000605860:PDGFRB protein, human