Clinical validation of single nucleotide polymorphisms (SNPs) as predictive biomarkers in localized and metastatic renal cell cancer (RCC).

Authors

null

Carmen Garrigos

Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain

Carmen Garrigos , Ana Salinas , Ricardo Melendez , Marta Espinosa , Iván Sánchez , Ignacio Osman , Rafael Medina , Miquel Taron , Ignacio Duran

Organizations

Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain, Hospital Universitario Virgen del Rocio, Sevilla, Spain, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain, Hospital Universitario Virgen del Rocío, Seville, Spain

Research Funding

Other Foundation

Background: SNPs predictive of survival outcomes in patients (pts) with localized and metastatic RCC have been identified previously by us [Garrigós C et al, 2017]. Fifteen SNPs in 9 genes involved in angiogenesis and metabolism of antiangiogenics were recognized as predictive/prognostic in a cohort of 102 pts. The aim of the present study is to validate these associations in an independent cohort of RCC pts Methods: Genotyping was performed in DNA isolated from paraffin-embedded tumor samples from 87 pts with localized and metastatic RCC. DNA was extracted by a commercial kit (QiAGEN) and amplified with a specific primers pool for each SNP as determined by the manufacturer (Lifetech). The 15 SNPs were individually genotyped by Real time quantitative PCR with specific primers and Taqman probes (Lifetech). The presence of the selected SNPs was correlated with clinical features such as disease free survival (DFS), progression free survival (PFS) and overall survival (OS). SPSS v24 was used for statistical analysis. Results: In the localized pts (n = 66), Fuhrman grades 3-4 and stage T3-T4 significantly associated with DFS (p = 0.025 and p = 0.004, respectively). The presence of allele C of rs307826 (FLT4 gene) correlated with a greater chance of relapse (p = 0.025) and also with a shorter DFS (21 vs 35 months, p = 0.007). For the metastatic pts (n = 21), allele C of rs307826 (FLT4 gene) and allele A of rs9800958 (PRKAR1B) were linked with a shorter PFS [(8 vs 18 months, p = 0.036) and (8 vs 17 months, p = 0.043) respectively]. In the localized cohort, allele T of rs2227543 (IL8 gene) was associated with longer OS (14 vs 3 months, p = 0.039) while allele G of rs10013228 (KDR gene) linked with worse OS (4 vs 17 months, p = 0.063). Conclusions: This analysis comes to confirm our previous observations that certain genotypes could be used as prognostic/predictive factors in RCC. This is particularly important in an era where multiple treatment options are available for this disease.

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Abstract Details

Meeting

2018 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Renal Cell Cancer

Track

Renal Cell Cancer

Sub Track

Renal Cell Cancer

Citation

J Clin Oncol 36, 2018 (suppl 6S; abstr 588)

DOI

10.1200/JCO.2018.36.6_suppl.588

Abstract #

588

Poster Bd #

F3

Abstract Disclosures

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