Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.
Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed hypermethylated in kidney cancer. Myopodin methylation status identified which patients showed a more aggressive clinical behavior and predicted antiangiogenic response. These observations support the clinical utility of an unmethylated myopodin as a prognostic and predictive biomarker in kidney cancer.
Translational Oncology Laboratory, Ikerbasque Research Program, Medicine Department, University of the Basque Country, Vitoria-Gasteiz, Spain.
N
N
Pompas-Veganzones
Translational Oncology Laboratory, Ikerbasque Research Program, Medicine Department, University of the Basque Country, Vitoria-Gasteiz, Spain.
V
V
Sandonis
Urology Department, Hospital Puerta Del Mar, Urology, Cadiz, Spain.
Alberto
A
Perez-Lanzac
Pathology Department, Hospital Puerta Del Mar, Cadiz, Spain.
M
M
Beltran
Urology Department, Hospital De Jerez, Jerez, Spain.
P
P
Beardo
Urology Department, Hospital De Jerez, Jerez, Spain.
A
A
Juárez
Urology Department, Hospital Virgen De Las Nieves, Granada, Spain.
F
F
Vazquez
Urology Department, Hospital Virgen De Las Nieves, Granada, Spain.
J M
JM
Cozar
Urology Department, Hospital Puerta Del Mar, Urology, Cadiz, Spain.
J L
JL
Alvarez-Ossorio
Translational Oncology Laboratory, Ikerbasque Research Program, Medicine Department, University of the Basque Country, Vitoria-Gasteiz, Spain. marta.sanchezcarbayo@ehu.eus.
Marta
M
Sanchez-Carbayo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; C503979:SYNPO2 protein, human
Antiangiogenic response; Kidney cancer; Methylation; Myopodin