Clinical and molecular prognostic and predictive biomarkers in clear cell renal cell cancer

Future Oncology

Volumn 10, Issue 15, 2014, Pages 2493-2508

  Czarnecka, Anna M ^a   Kukwa, Wojciech ^b   Kornakiewicz, Anna ^a,b   Lian, Fei ^c   Szczylik, Cezary ^a  

^a MILITARY INSTITUTE OF MEDICINE   (Poland)

^b MEDICAL UNIVERSITY OF WARSAW   (Poland)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

biomarker; HIF; prediction; prognosis; renal cancer; sorafenib; sunitinib; VEGF

Indexed keywords

BIOLOGICAL MARKER; MOLECULAR MARKER;

CANCER PATIENT; CANCER PROGNOSIS; HIGH RISK PATIENT; HUMAN; KIDNEY CARCINOMA; METASTASIS; MODEL; PREDICTIVE VALUE; REVIEW;

EID: 84920056780     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.14.162     Document Type: Review

References (106)

1. Strimbu K, Tavel JA. What are biomarkers? Curr. Opin. HIV AIDS 5(6), 463-466 (2010).
2. Shoji S, Nakano M, Sato H et al. The current status of tailor-made medicine with molecular biomarkers for patients with clear cell renal cell carcinoma. Clin. Exp. Metastasis 31(1), 111-134 (2013).
3. Lopez JI. Renal tumors with clear cells. A review. Pathol. Res. Pract. 209(3), 137-146 (2013).
4. Moch H. An overview of renal cell cancer: pathology and genetics. Semin. Cancer Biol. 23(1), 3-9 (2013).
5. Italiano A. Prognostic or predictive? It's time to get back to definitions! J. Clin. Oncol. 29(35), 4718-4719 (2011).
6. Porta C, Bellmunt J, Eisen T, Szczylik C, Mulders P. Treating the individual: the need for a patient-focused approach to the management of renal cell carcinoma. Cancer Treat. Rev. 36(1), 16-23 (2012).
7. Cheng L, Zhang S, Maclennan GT, Lopez-Beltran A, Montironi R. Molecular and cytogenetic insights into the pathogenesis, classification, differential diagnosis, and prognosis of renal epithelial neoplasms. Hum. Pathol. 40(1), 10-29 (2009).
8. Kapur P, Christie A, Raman JD et al. BAP1 immunohistochemistry in a multi-institutional cohort predicts outcomes in patients with clear cell renal cell carcinoma. J. Urol. 191(3), 603-610 (2013).
9. Shuch B, Li Z, Belldegrun AS. Carbonic anhydrase IX and renal cell carcinoma: prognosis, response to systemic therapy, and future vaccine strategies. BJU Int.101(Suppl. 4), 25-30 (2008).
10. Rink M, Chun FK, Robinson B et al. Tissue-based molecular markers for renal cell carcinoma. Minerva Urol. Nefrol. 63(4), 293-308 (2011).
11. Vilella-Arias SA, Rocha RM, Da Costa WH et al. Loss of caspase 7 expression is associated with poor prognosis in renal cell carcinoma clear cell subtype. Urology 82(4), 974.e1-974.e7 (2013).
12. Steffens S, Schrader AJ, Blasig H et al. Caveolin 1 protein expression in renal cell carcinoma predicts survival. BMC Urol. 11, 25 (2011).
13. Dubinski W, Gabril M, Iakovlev VV et al. Assessment of the prognostic significance of endoglin (CD105) in clear cell renal cell carcinoma using automated image analysis. Hum. Pathol. 43(7), 1037-1043 (2012).
14. Costa WH, Rocha RM, Cunha IW, Fonseca FP, Guimaraes GC, Zequi Sde C. CD133 immunohistochemical expression predicts progression and cancer-related death in renal cell carcinoma. World J. Urol. 30(4), 553-558 (2012).
15. Yoo SH, Lee K, Chae JY, Moon KC. CD151 expression can predict cancer progression in clear cell renal cell carcinoma. Histopathology 58(2), 191-197 (2011).
16. Macher-Goeppinger S, Bermejo JL, Wagener N et al. Expression and prognostic relevance of the death receptor CD95 (Fas/APO1) in renal cell carcinomas. Cancer Lett. 301(2), 203-211 (2011).
17. Yu ZH, Zhang Q, Wang YD et al. Overexpression of cyclooxygenase-1 correlates with poor prognosis in renal cell carcinoma. Asian Pac. J. Cancer Prev. 14(6), 3729-3734 (2013).
18. D'alterio C, Cindolo L, Portella L et al. Differential role of CD133 and CXCR4 in renal cell carcinoma. Cell Cycle 9(22), 4492-4500 (2010).
19. Wu S, Wang Y, Sun L et al. Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma. BMC Cancer 11, 413 (2011).
20. Sato M, Nakai Y, Nakata W et al. EMMPRIN promotes angiogenesis, proliferation, invasion and resistance to sunitinib in renal cell carcinoma, and its level predicts patient outcome. PLoS ONE 8(9), e74313 (2013).
21. Bot BM, Eckel-Passow JE, Legrand SN et al. Expression of endothelin 2 and localized clear cell renal cell carcinoma. Hum. Pathol. 43(6), 843-849 (2012).
22. Wagener N, Macher-Goeppinger S, Pritsch M et al. Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma. BMC Cancer 10, 524 (2010).
23. Xu B, Abourbih S, Sircar K et al. Enhancer of zeste homolog 2 expression Is associated with metastasis and adverse clinical outcome in clear cell renal cell carcinoma: a comparative study and review of the literature. Arch. Pathol. Lab. Med. 137(10), 1326-1336 (2013).
24. Qayyum T, Mcardle PA, Lamb GW et al. Expression and prognostic significance of Src family members in renal clear cell carcinoma. Br. J. Cancer 107(5), 856-863 (2012).
25. Wei C, Wu S, Li X et al. High expression of FER tyrosine kinase predicts poor prognosis in clear cell renal cell carcinoma. Oncol. Lett. 5(2), 473-478 (2013).
26. Searchfield L, Price SA, Betton G, Jasani B, Riccardi D, Griffiths DF. Glutathione S-transferases as molecular markers of tumor progression and prognosis in renal cell carcinoma. Histopathology 58(2), 180-190 (2011).
27. Kren L, Valkovsky I, Dolezel J et al. HLA-G and HLA-E specific mRNAs connote opposite prognostic significance in renal cell carcinoma. Diagn. Pathol. 7, 58 (2012).
28. Wu K, Xu L, Zhang L, Lin Z, Hou J. High Jagged1 expression predicts poor outcome in clear cell renal cell carcinoma. Jpn J. Clin. Oncol. 41(3), 411-416 (2011).
29. Slaby O, Redova M, Poprach A et al. Identification of MicroRNAs associated with early relapse after nephrectomy in renal cell carcinoma patients. Genes Chromosomes Cancer 51(7), 707-716 (2012).
30. Sgambato A, Camerini A, Genovese G et al. Loss of nuclear p27(kip1) and alpha-dystroglycan is a frequent event and is a strong predictor of poor outcome in renal cell carcinoma. Cancer Sci. 101(9), 2080-2086 (2010).
31. Zubac DP, Wentzel-Larsen T, Seidal T, Bostad L. Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy. BMC Urol. 10, 20 (2010).
32. Da Costa WH, Rezende M, Rocha RM et al. PBRM1, a SWI/SNF complex subunit is a prognostic marker in clear cell renal cell carcinoma. BJU Int. 113(5b), E157-E163 (2013).
33. Grunwald V, Karakiewicz PI, Bavbek SE et al. An international expanded-access programme of everolimus: addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy. Eur. J. Cancer 48(3), 324-332 (2012).
34. Wu XR, Sha JJ, Liu DM et al. High expression of P53-induced Ring-h2 protein is associated with poor prognosis in clear cell renal cell carcinoma. Eur. J. Surg. Oncol. 39(1), 100-106 (2013).
35. Yuan J, Jiang B, Zhao H, Huang Q. Prognostic implication of TIM-3 in clear cell renal cell carcinoma. Neoplasma 61(1), 35-40 (2014).
36. Kruck S, Eyrich C, Scharpf M et al. Impact of an altered Wnt1/beta-catenin expression on clinicopathology and prognosis in clear cell renal cell carcinoma. Int. J. Mol. Sci. 14(6), 10944-10957 (2013).
37. Sun D, Lu J, Ding K et al. The expression of Eg5 predicts a poor outcome for patients with renal cell carcinoma. Med. Oncol. 30(1), 476 (2013).
38. Wu XR, Chen YH, Liu DM et al. Increased expression of forkhead box M1 protein is associated with poor prognosis in clear cell renal cell carcinoma. Med. Oncol. 30(1), 346 (2013).
39. Xue YJ, Xiao RH, Long DZ et al. Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma. J. Transl. Med. 10(1), 200-212 (2012).
40. Yang FQ, Yang FP, Li W et al. Foxl1 inhibits tumor invasion and predicts outcome in human renal cancer. Int. J. Clin. Exp. Pathol. 7(1), 110-122 (2014).
41. Darwish OM, Kapur P, Youssef RF et al. Cumulative number of altered biomarkers in mammalian target of rapamycin pathway is an independent predictor of outcome in patients with clear cell renal cell carcinoma. Urology 81(3), 581-586 (2013).
42. Schultz L, Chaux A, Albadine R. et al. Immunoexpression status and prognostic value of mTOR and hypoxia-induced pathway members in primary and metastatic clear cell renal cell carcinomas. Am. J. Surg. Pathol. 35(10), 1549-1556 (2011).
43. Noh SJ, Kang MJ, Kim KM et al. Acetylation status of P53 and the expression of DBC1, SIRT1, and androgen receptor are associated with survival in clear cell renal cell carcinoma patients. Pathology 45(6), 574-580 (2013).
44. Parker AS, Leibovich BC, Lohse CM et al. Development and evaluation of BioScore: a biomarker panel to enhance prognostic algorithms for clear cell renal cell carcinoma. Cancer 115(10), 2092-2103 (2009).
45. Klatte T, Seligson DB, Larochelle J et al. Molecular signatures of localized clear cell renal cell carcinoma to predict disease-free survival after nephrectomy. Cancer Epidemiol. Biomarkers Prev. 18(3), 894-900 (2009).
46. Harada K, Miyake H, Kusuda Y, Fujisawa M. Expression of epithelial-mesenchymal transition markers in renal cell carcinoma: impact on prognostic outcomes in patients undergoing radical nephrectomy. BJU Int. 110(11 Pt C), E1131-E1137 (2012).
47. Wang L, Chen W, Gao L et al. High expression of CXCR4, CXCR7 and SDF-1 predicts poor survival in renal cell carcinoma. World J. Surg. Oncol. 10, 212 (2012).
48. Sakai I, Miyake H, Takenaka A, Fujisawa M. Expression of potential molecular markers in renal cell carcinoma: impact on clinicopathological outcomes in patients undergoing radical nephrectomy. BJU Int. 104(7), 942-946 (2009).
49. Klatte T, Seligson DB, Leppert JT et al. The chemokine receptor CXCR3 is an independent prognostic factor in patients with localized clear cell renal cell carcinoma. J. Urol. 179(1), 61-66 (2008).
50. Masui O, White NM, Desouza LV et al. Quantitative proteomic analysis in metastatic renal cell carcinoma reveals a unique set of proteins with potential prognostic significance. Mol. Cell. Proteomics 12(1), 132-144 (2013).
51. Chen D, Gassenmaier M, Maruschke M et al. Expression and prognostic significance of a comprehensive epithelial-mesenchymal transition gene set in renal cell carcinoma. J. Urol. 191(2), 479-486 (2013).
52. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J. Clin. Oncol. 17(8), 2530-2540 (1999).
53. Armstrong AJ, George DJ, Halabi S. Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin. J. Clin. Oncol. 30(27), 3402-3407 (2012).
54. Choi Y, Park B, Kim K et al. Erythrocyte sedimentation rate and anaemia are independent predictors of survival in patients with clear cell renal cell carcinoma. Br. J. Cancer 108(2), 387-394 (2013).
55. De Martino M, Klatte T, Seemann C et al. Validation of serum C-reactive protein (CRP) as an independent prognostic factor for disease-free survival in patients with localised renal cell carcinoma (RCC). BJU Int. 111(8), E348-E353 (2013).
56. Sim SH, Messenger MP, Gregory WM et al. Prognostic utility of pre-operative circulating osteopontin, carbonic anhydrase IX and CRP in renal cell carcinoma. Br. J. Cancer 107(7), 1131-1137 (2012).
57. Seidel C, Busch J, Weikert S et al. Progression free survival of first line vascular endothelial growth factor-targeted therapy is an important prognostic parameter in patients with metastatic renal cell carcinoma. Eur. J. Cancer 48(7), 1023-1030 (2012).
58. Zolnierek J, Nurzynski P, Langiewicz P et al. Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases. J. Cancer Res. Clin. Oncol. 136(3), 371-378 (2011).
59. Bex A, Gore M, Mulders P, Sternberg CN. Recent advances in the treatment of advanced renal cell carcinoma: towards multidisciplinary personalized care. BJU Int. 110(9), 1289-1300 (2012).
60. Escudier B, Szczylik C, Porta C, Gore M. Treatment selection in metastatic renal cell carcinoma: expert consensus. Nat. Rev. Clin. Oncol. 9(6), 327-337 (2012).
61. Gore ME, Bellmunt J, Eisen T et al. Evaluation of treatment options for patients with advanced renal cell carcinoma: assessment of appropriateness, using the validated semi-quantitative RAND corporation/University of California, Los Angeles methodology. Eur. J. Cancer 48(7), 1038-1047 (2012).
62. Bui MH, Seligson D, Han KR et al. Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. Clin. Cancer Res. 9(2), 802-811 (2003).
63. Patard JJ, Fergelot P, Karakiewicz PI et al. Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma. Int. J. Cancer 123(2), 395-400 (2008).
64. Muriel Lopez C, Esteban E, Berros JP et al. Prognostic factors in patients with advanced renal cell carcinoma. Clin. Genitourin. Cancer 10(4), 262-270 (2012).
65. Phuoc NB, Ehara H, Gotoh T et al. Prognostic value of the co-expression of carbonic anhydrase IX and vascular endothelial growth factor in patients with clear cell renal cell carcinoma. Oncol. Rep. 20(3), 525-530 (2008).
66. Zhang BY, Thompson RH, Lohse CM et al. Carbonic anhydrase IX (CAIX) is not an independent predictor of outcome in patients with clear cell renal cell carcinoma (ccRCC) after long-term follow-up. BJU Int. 111(7), 1046-1053 (2013).
67. Klatte T, Seligson DB, Riggs SB et al. Hypoxia-inducible factor 1 alpha in clear cell renal cell carcinoma. Clin. Cancer Res. 13(24), 7388-7393 (2007).
68. Minardi D, Lucarini G, Filosa A et al. Prognostic role of tumor necrosis, microvessel density, vascular endothelial growth factor and hypoxia inducible factor-1alpha in patients with clear cell renal carcinoma after radical nephrectomy in a long term follow-up. Int. J. Immunopathol. Pharmacol. 21(2), 447-455 (2008).
69. Ku JH, Park YH, Myung JK, Moon KC, Kwak C, Kim HH. Expression of hypoxia inducible factor-1 and 2 in conventional renal cell carcinoma with or without sarcomatoid differentiation. Urol. Oncol. 29(6), 731-737 (2011).
70. Biswas S, Charlesworth PJ, Turner GD et al. CD31 angiogenesis and combined expression of HIF-1alpha and HIF-2alpha are prognostic in primary clear-cell renal cell carcinoma (CC-RCC), but HIFalpha transcriptional products are not: implications for antiangiogenic trials and HIFalpha biomarker studies in primary CC-RCC. Carcinogenesis 33(9), 1717-1725 (2012).
71. Dorevi G, Matusan-Ilijas K, Babarovi E, Hadzisejdi I, Grahovac B, Jonji N. Hypoxia inducible factor-1alpha correlates with vascular endothelial growth factor A and C indicating worse prognosis in clear cell renal cell carcinoma. J. Exp. Clin. Cancer Res. 28(1), 40-47 (2009).
72. Cowey CL, Rathmell WK. VHL gene mutations in renal cell carcinoma: role as a biomarker of disease outcome and drug efficacy. Curr. Oncol. Rep. 11(2), 94-101 (2009).
73. Bellmunt J, Eisen T, Szczylik C, Mulders P, Porta C. A new patient-focused approach to the treatment of metastatic renal cell carcinoma: establishing customized treatment options. BJU Int. 107(8), 1190-1199 (2011).
74. Porta C, Szczylik C, Escudier B. Combination or sequencing strategies to improve the outcome of metastatic renal cell carcinoma patients: a critical review. Crit. Rev. Oncol. Hematol. 82(3), 323-337 (2012).
75. Osanto S, Qin Y, Buermans HP et al. Genome-wide microRNA expression analysis of clear cell renal cell carcinoma by next generation deep sequencing. PLoS One 7(6), e38298 (2012).
76. Motzer RJ, Hutson TE, Tomczak P et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 27(22), 3584-3590 (2009).
77. Beck J, Procopio G, Bajetta E et al. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann. Oncol. 22(8), 1812-1823 (2011).
78. Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J. Clin. Oncol. 28(6), 1061-1068 (2011).
79. Rini BI, Escudier B, Tomczak P et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378(9807), 1931-1939 (2012).
80. Rodriguez-Antona C, Garcia-Donas J. Constitutional genetic variants as predictors of antiangiogenic therapy outcome in renal cell carcinoma. Pharmacogenomics 13(14), 1621-1633 (2012).
81. Escudier B, Szczylik C, Porta C, Gore M. Treatment selection in metastatic renal cell carcinoma: expert consensus. Nat. Rev. Clin. Oncol. 9(6), 327-337 (2012).
82. Sternberg CN, Hawkins RE, Wagstaff J et al. A randomised, double-blind Phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur. J. Cancer 49(6), 1287-1296 (2013).
83. Michaelson MD, Stadler WM. Predictive markers in advanced renal cell carcinoma. Semin. Oncol. 40(4), 459-464 (2013).
84. Szmit S, Langiewicz P, Zlnierek J et al. Hypertension as a predictive factor for survival outcomes in patients with metastatic renal cell carcinoma treated with sunitinib after progression on cytokines. Kidney Blood Press. Res. 35(1), 18-25 (2012).
85. Szmit S, Zaborowska M, Wasko-Grabowska A et al. Cardiovascular comorbidities for prediction of progression-free survival in patients with metastatic renal cell carcinoma treated with sorafenib. Kidney Blood Press. Res. 35(6), 468-476 (2012).
86. Escudier B, Eisen T, Stadler WM et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J. Clin. Oncol. 27(20), 3312-3318 (2009).
87. Zhang HL, Zhu Y, Wang CF et al. Erythrocyte sedimentation rate kinetics as a marker of treatment response and predictor of prognosis in Chinese metastatic renal cell carcinoma patients treated with sorafenib. Int. J. Urol. 18(6), 422-430 (2011).
88. Pena C, Lathia C, Shan M, Escudier B, Bukowski RM. Biomarkers predicting outcome in patients with advanced renal cell carcinoma: results from sorafenib Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial. Clin. Cancer Res. 16(19), 4853-4863 (2010).
89. Fujita T, Iwamura M, Ishii D et al. C-reactive protein as a prognostic marker for advanced renal cell carcinoma treated with sunitinib. Int. J. Urol. 19(10), 908-913 (2012).
90. Dornbusch J, Zacharis A, Meinhardt M et al. Analyses of potential predictive markers and survival data for a response to sunitinib in patients with metastatic renal cell carcinoma. PLoS ONE 8(9), e76386 (2013).
91. Scartozzi M, Bianconi M, Faloppi L et al. VEGF and VEGFR polymorphisms affect clinical outcome in advanced renal cell carcinoma patients receiving first-line sunitinib. Br. J. Cancer 108(5), 1126-1132 (2013).
92. Beuselinck B, Karadimou A, Lambrechts D et al. Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib. Br. J. Cancer 108(4), 887-900 (2013).
93. Paule B, Bastien L, Deslandes E et al. Soluble isoforms of vascular endothelial growth factor are predictors of response to sunitinib in metastatic renal cell carcinomas. PLoS ONE 5(5), e10715 (2010).
94. De Martino M, Hoetzenecker K, Ankersmit HJ et al. Serum 20S proteasome is elevated in patients with renal cell carcinoma and associated with poor prognosis. Br. J. Cancer 106(5), 904-908 (2012).
95. Vermaat JS, Gerritse FL, van der Veldt AA et al. Validation of serum amyloid alpha as an independent biomarker for progression-free and overall survival in metastatic renal cell cancer patients. Eur. Urol. 62(4), 685-695 (2012).
96. Gamez-Pozo A, Anton-Aparicio LM, Bayona C et al. MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients. Neoplasia 14(12), 1144-1152 (2012).
97. Choueiri TK, Regan MM, Rosenberg JE et al. Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy. BJU Int. 106(6), 772-778 (2010).
98. Hegde PS, Jubb AM, Chen D et al. Predictive impact of circulating vascular endothelial growth factor in four phase III trials evaluating bevacizumab. Clin. Cancer Res. 19(4), 929-937 (2013).
99. Lambrechts D, Claes B, Delmar P et al. VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol. 13(7), 724-733 (2012).
100. Choueiri TK, Fay AP, Gagnon R et al. The role of aberrant VHL/HIF pathway elements in predicting clinical outcome to pazopanib therapy in patients with metastatic clear-cell renal cell carcinoma. Clin. Cancer Res. 19(18), 5218-5226 (2013).
101. Tran HT, Liu Y, Zurita AJ et al. Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of Phase 2 and Phase 3 trials. Lancet Oncol. 13(8), 827-837 (2012).
102. Gigante M, Li G, Ferlay C et al. Prognostic value of serum CA9 in patients with metastatic clear cell renal cell carcinoma under targeted therapy. Anticancer Res. 32(12), 5447-5451 (2012).
103. Figlin RA, De Souza P, Mcdermott D et al. Analysis of PTEN and HIF-1alpha and correlation with efficacy in patients with advanced renal cell carcinoma treated with temsirolimus versus interferon-alpha. Cancer 115(16), 3651-3660 (2009).
104. Vrdoljak E, Ciuleanu T, Kharkevich G et al. Optimizing treatment for patients with metastatic renal cell carcinoma in the Central and Eastern European region. Expert Opin. Pharmacother. 13(2), 159-174 (2012).
105. Maroto P, Rini B. Molecular biomarkers in advanced renal cell carcinoma. Clin. Cancer Res. 20(8), 2060-2071 (2014).
106. Kim HS, Kim WS, Park SH et al. Molecular biomarkers for advanced renal cell carcinoma: implications for prognosis and therapy. Urol. Oncol. 28(2), 157-163 (2010).