Systematic Review: ClearCode 34 - A Validated Prognostic Signature in Clear Cell Renal Cell Carcinoma (ccRCC)

Overview

Journal Kidney Cancer

Date 2018 Oct 16

PMID 30320241

Citations 23

Authors

Pooja Ghatalia

W Kimryn Rathmell

Affiliations

Soon will be listed here.

Abstract

The standard of care of patients with localized clear cell RCC (ccRCC) is observation after nephrectomy. However, a third of these patients have local or distant recurrence. Along with basic clinical and pathologic variables like stage, necrosis and grade, robust molecular based prognostic markers are needed that could help better predict groups of patients who will most benefit from such adjuvant treatment approaches. ccA/ccB classification was developed to classify ccRCC patients into high and low risk based on gene expression patterns. ClearCode 34 is a genetic signature that was developed from the ccA/ccB classification to predict recurrence in localized ccRCC patients. This signature has been validated in several patient cohorts and is ready for future testing in a variety of clinical scenarios. This review will evaluate the molecular signature ClearCode34, discuss its role in predicting recurrence and consider the rational application of this example of a molecular biomarker in the management of ccRCC.

Citing Articles

Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.

Rossi S, Dombrowe V, Godfrey L, Bucaciuc Mracica T, Pita S, Milne-Clark T Oncogene. 2025; .

PMID: 39824946 DOI: 10.1038/s41388-024-03270-3.

Perioperative systemic therapy in high-risk renal cell carcinoma following nephrectomy: a narrative review.

Khorasanchi A, Goodstein T, Dason S, Singer E, Zimmerman D, Yang Y Transl Cancer Res. 2024; 13(11):6511-6528.

PMID: 39697735 PMC: 11651769. DOI: 10.21037/tcr-24-16.

Development and evaluation of a disulfidoptosis-related lncRNA index for prognostication in clear cell renal cell carcinoma.

Guan R, Zuo Y, Du Q, Zhang A, Wu Y, Zheng J Heliyon. 2024; 10(12):e32294.

PMID: 38975147 PMC: 11225747. DOI: 10.1016/j.heliyon.2024.e32294.

Identifying genes associated with disease outcomes using joint sparse canonical correlation analysis-An application in renal clear cell carcinoma.

Dutta D, Sen A, Satagopan J Genet Epidemiol. 2024; 48(8):414-432.

PMID: 38751238 PMC: 11589067. DOI: 10.1002/gepi.22566.

Identification of novel snoRNA-based biomarkers for clear cell renal cell carcinoma from urine-derived extracellular vesicles.

Grutzmann K, Salomo K, Kruger A, Lohse-Fischer A, Erdmann K, Seifert M Biol Direct. 2024; 19(1):38.

PMID: 38741178 PMC: 11089706. DOI: 10.1186/s13062-024-00467-0.

References

Zigeuner R, Hutterer G, Chromecki T, Imamovic A, Kampel-Kettner K, Rehak P . External validation of the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score for clear-cell renal cell carcinoma in a single European centre applying routine pathology. Eur Urol. 2008; 57(1):102-9. DOI: 10.1016/j.eururo.2008.11.033. View

Sternberg C, Davis I, Mardiak J, Szczylik C, Lee E, Wagstaff J . Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010; 28(6):1061-8. DOI: 10.1200/JCO.2009.23.9764. View

Linehan W, Spellman P, Ricketts C, Creighton C, Fei S, Davis C . Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. N Engl J Med. 2015; 374(2):135-45. PMC: 4775252. DOI: 10.1056/NEJMoa1505917. View

Davis C, Ricketts C, Wang M, Yang L, Cherniack A, Shen H . The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014; 26(3):319-330. PMC: 4160352. DOI: 10.1016/j.ccr.2014.07.014. View

Brannon A, Reddy A, Seiler M, Arreola A, Moore D, Pruthi R . Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns. Genes Cancer. 2010; 1(2):152-163. PMC: 2943630. DOI: 10.1177/1947601909359929. View

Motzer R, Haas N, Donskov F, Gross-Goupil M, Varlamov S, Kopyltsov E . Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma. J Clin Oncol. 2017; 35(35):3916-3923. PMC: 6018511. DOI: 10.1200/JCO.2017.73.5324. View

Serie D, Joseph R, Cheville J, Ho T, Parasramka M, Hilton T . Clear Cell Type A and B Molecular Subtypes in Metastatic Clear Cell Renal Cell Carcinoma: Tumor Heterogeneity and Aggressiveness. Eur Urol. 2016; 71(6):979-985. PMC: 5401797. DOI: 10.1016/j.eururo.2016.11.018. View

. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013; 499(7456):43-9. PMC: 3771322. DOI: 10.1038/nature12222. View

Callea M, Albiges L, Gupta M, Cheng S, Genega E, Fay A . Differential Expression of PD-L1 between Primary and Metastatic Sites in Clear-Cell Renal Cell Carcinoma. Cancer Immunol Res. 2015; 3(10):1158-64. PMC: 4596765. DOI: 10.1158/2326-6066.CIR-15-0043. View

10.

Eckel-Passow J, Igel D, Serie D, Joseph R, Ho T, Cheville J . Assessing the clinical use of clear cell renal cell carcinoma molecular subtypes identified by RNA expression analysis. Urol Oncol. 2014; 33(2):68.e17-23. DOI: 10.1016/j.urolonc.2014.07.019. View

11.

Haas N, Manola J, Uzzo R, Flaherty K, Wood C, Kane C . Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016; 387(10032):2008-16. PMC: 4878938. DOI: 10.1016/S0140-6736(16)00559-6. View

12.

Motzer R, Ravaud A, Patard J, Pandha H, George D, Patel A . Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results. Eur Urol. 2017; 73(1):62-68. PMC: 6684251. DOI: 10.1016/j.eururo.2017.09.008. View

13.

Ravaud A, Motzer R, Pandha H, George D, Pantuck A, Patel A . Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. N Engl J Med. 2016; 375(23):2246-2254. DOI: 10.1056/NEJMoa1611406. View

14.

Brooks S, Brannon A, Parker J, Fisher J, Sen O, Kattan M . ClearCode34: A prognostic risk predictor for localized clear cell renal cell carcinoma. Eur Urol. 2014; 66(1):77-84. PMC: 4058355. DOI: 10.1016/j.eururo.2014.02.035. View

15.

Buttner F, Winter S, Rausch S, Reustle A, Kruck S, Junker K . Survival Prediction of Clear Cell Renal Cell Carcinoma Based on Gene Expression Similarity to the Proximal Tubule of the Nephron. Eur Urol. 2015; 68(6):1016-20. DOI: 10.1016/j.eururo.2015.05.045. View

16.

Brannon A, Haake S, Hacker K, Pruthi R, Wallen E, Nielsen M . Meta-analysis of clear cell renal cell carcinoma gene expression defines a variant subgroup and identifies gender influences on tumor biology. Eur Urol. 2011; 61(2):258-68. PMC: 3244546. DOI: 10.1016/j.eururo.2011.10.007. View

17.

Gerlinger M, Rowan A, Horswell S, Math M, Larkin J, Endesfelder D . Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012; 366(10):883-892. PMC: 4878653. DOI: 10.1056/NEJMoa1113205. View

18.

Lam J, Shvarts O, Leppert J, Pantuck A, Figlin R, Belldegrun A . Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma based on a validated prognostic nomogram and risk group stratification system. J Urol. 2005; 174(2):466-72. DOI: 10.1097/01.ju.0000165572.38887.da. View

19.

de Velasco G, Culhane A, Fay A, Hakimi A, Voss M, Tannir N . Molecular Subtypes Improve Prognostic Value of International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Model. Oncologist. 2017; 22(3):286-292. PMC: 5344647. DOI: 10.1634/theoncologist.2016-0078. View

20.

Rini B, Goddard A, Knezevic D, Maddala T, Zhou M, Aydin H . A 16-gene assay to predict recurrence after surgery in localised renal cell carcinoma: development and validation studies. Lancet Oncol. 2015; 16(6):676-85. DOI: 10.1016/S1470-2045(15)70167-1. View