Single-nucleotide polymorphisms (SNPs) associated with outcomes in patients with localized and metastatic renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 437-437
Author(s):  
Carmen Garrigos ◽  
Marta Espinosa ◽  
Ignacio Osman ◽  
Rainiero Ávila ◽  
Rafael Medina ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Snp Data ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Vegf Isoforms

437 Background: Despite major advances in the knowledge of the molecular basis of RCC, prognosis is still defined using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. The aim of this work is analyzing the expression and determining the prognostic and predictive value of 64 key SNPs in 18 genes related with angiogenesis or metabolism of antiangiogenics in patients (pts) with both localized and advanced RCC treated at Hospital Universitario Virgen del Rocío. Methods: DNA from formalin fixed paraffin embedded tumor and non-tumor samples from 99 pts with RCC (26 advanced/ 73 localized) was extracted with QiAGEN Kit and amplified with a specific primers pool for every SNP as determined by the manufacturer (Lifetech). 64 SNPs were chosen based on their Minor Allele Frequency by HapMap, linkage disequilibrium by Haploview, and information from SNP data base (dSNP) and were studied by TaqMan OpenArray (Lifetech). The presence of the selected SNPs was correlated with clinical features, disease free survival (DFS), overall survival (OS), and response to treatment (RR). SPSS v16 was utilized for statistical analyses. Results: In pts with localized RCC, 6 SNPs in 3 genes involved in angiogenesis predicted for worse DFS (VEGFR2: rs10013228, rs2071559; PDGFRA: rs2228230) and shorter OS (VEGFR2: rs10013228; VEGFR3: rs6877011, rs307826) (p<0.05). In the advanced setting, 7 SNPs in genes related to both angiogenesis and metabolism of antiangiogenics determined inferior OS (IL8: rs2227543, NR1l2: rs3814055, NR1l3: rs2307424, PDGFA: rs9800958, PDGFRB: rs2302273) and worse RR (VEGFA: rs699947, rs3025010 p<0.01)). Additionally 3 SNPs in PDGFR-B and VEGF isoforms predicted for better RR (PDGFRB: rs17708574 (p=0.08), VEGFB: rs594942 (p=0.03), VEGFC: rs2016110 (p=0.07). Conclusions: Genetic analysis of RCC patients might provide valuable prognostic/predictive information. A set of SNPs in genes critical to angiogenesis and metabolism of antiangiogenics seem to determine post-surgical outcomes and treatment response in our series. These results are promising. Validation of the results is ongoing.

Predicting outcomes in renal cell cancer: The role of single nucleotide polymorphisms (SNPs).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16074-e16074
Author(s):  
Carmen Garrigos ◽  
Marta Espinosa ◽  
Ignacio Osman ◽  
Rainiero Ávila ◽  
Rafael Medina ◽  
...  
Keyword(s):  
Cell Cancer ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Significant Snps ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Snp Data ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

e16074 Background: Despite major advances in the knowledge of the molecular basis of RCC, prognosis is still defined mostly using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. The aim of this work is analyzing the expression and determining the prognostic and predictive value of 64 key SNPs in 18 genes related with angiogenesis or metabolism of antiangiogenics in two cohorts of RCC patients (pts) [localized and advanced] RCC treated at our institution. Methods: DNA from formalin fixed paraffin embedded tumor and non-tumor samples from 99 pts with RCC (26 advanced/ 73 localized) was extracted with QiAGEN Kit and amplified with a specific primers pool for every SNP as determined by the manufacturer (Lifetech). Sixty-four SNPs were chosen based on their Minor Allele Frequency by HapMap, linkage disequilibrium by Haploview and information from SNP data base (dSNP) and were studied by TaqMan OpenArray (Lifetech). Statistically significant SNPs were validated in an external cohort by individual assays. The presence of the selected SNPs was correlated with clinical features, disease free survival (DFS), overall survival (OS) and response to treatment (RR). SPSS v20 was utilized for statistical analyses. Results: In pts with localized RCC, 2 SNPs in 2 genes involved in angiogenesis showed a protective effect (VEGFR2: rs2071559, PDGFRA: rs4358459) and others SNPs predicted for worse DFS (VEGFR2: rs10013228, rs1870377, PDGFRA: rs2228230) and shorter OS (VEGFR2: rs2305948, rs10013228; VEGFR3: rs6877011, rs307826) (p < 0.05). In the advanced setting, 6 SNPs in genes related to both angiogenesis and metabolism of antiangiogenics were statistically implicated in OS (IL8: rs2227543, PDGFA: rs9800958, PDGFRB: rs2302273 (p≤0.05)) and RR (VEGFA: rs699947, rs3025010, VEGFB: rs594942 (p < 0.03)). These 14 SNPs are currently being validated in an external cohort of 80 patients with RCC and this data will be presented. Conclusions: These SNPs in genes critical to angiogenesis and metabolism of antiangiogenics might be used as potential prognostic/predictive biomarkers. Prospective validation is ongoing.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

Effect of adding oxaliplatin to adjuvant 5-fluorouracil/leucovorin (5FU/LV) in patients with defective mismatch repair (dMMR) colon cancer stage II and III included in the MOSIAC study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3524-3524 ◽  
Author(s):  
Jean-François Flejou ◽  
Thierry André ◽  
Benoist Chibaudel ◽  
Aurelie Scriva ◽  
Tamas Hickish ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Ii ◽  
Stage Iii ◽  
Free Survival ◽  
Translational Study ◽  
Hazard Ratios ◽  
Formalin Fixed Paraffin ◽  
Three Samples ◽  
Evaluable Population ◽  
Formalin Fixed Paraffin Embedded

3524 Background: The MOSAIC study (André T, N Engl J Med, 2004) demonstrated that adding oxaliplatin to adjuvant 5FU and LV improved three-year disease-free survival (DFS) in stage II and III resected CC. Efficacy of FOLFOX4 in pts with dMMR stage III was suggested in a retrospective study (Zaanan A, Ann Oncol 2010). Methods: Of the 2,246 pts included in MOSAIC study, formalin-fixed, paraffin-embedded (FFPE) tissue blocks or slides from 1,019 pts were obtained. Thirty-three samples with insufficient tumor tissue were excluded from this translational study. MMR status was determined by immunohistochemistry (IHC) analysis of the protein products of MLH1, MSH2, PMS2, and MSH6 genes. Results: A total of 986 pts (44%) were evaluable for MMR status and MMR status was not evaluable for 1,260 pts (56%). Relapse-free survival (RFS), DFS and overall survival (OS) were similar in both, MMR and MMR not evaluable population. Ninety (9.1%) and 896 (90.9%) pts had dMMR and proficient MMR (pMMR) CC, respectively. Of the patients with 90 dMMR CC, 45 pts had stage II and 45 stage III. Hazard Ratios (HRs) for stage II and III dMMR are 0.52 (0.21–1.28) for RFS, 0.52 (0.24–1.14) for DFS, and 0.45 (0.19–1.05) for OS, respectively. HR for stage III dMMR are 0.56 (0.19–1.61) for RFS, 0.51 (0.18–1.41) for DFS, and 0.44 (0.15–1.34) for OS, respectively. HR for stage II dMMR are 0.64 (0.11–3.70) for RFS, 0.60 (0.17–2.09) for DFS, and 0.52 (0.13–2.10) for OS, respectively. Conclusions: Analyses ofcolon cancerMMR status in pts included in the MOSAIC study support the use of FOLFOX4 in pts with dMMR stage III cancer. Clinical trial information: NCT00275210. [Table: see text]

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

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 588-588 ◽  
Author(s):  
Carmen Garrigos ◽  
Ana Salinas ◽  
Ricardo Melendez ◽  
Marta Espinosa ◽  
Iván Sánchez ◽  
...  
Keyword(s):  
Treatment Options ◽  
Cell Cancer ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
Specific Primers ◽  
Free Survival ◽  
Multiple Treatment ◽  
Metastatic Rcc

588 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.

Genetic Activation of the MET Pathway and Prognosis of Patients With High-Risk, Radically Resected Gastric Cancer

2011 ◽  
Vol 29 (36) ◽  
pp. 4789-4795 ◽  
Author(s):  
Francesco Graziano ◽  
Nadia Galluccio ◽  
Paola Lorenzini ◽  
Annamaria Ruzzo ◽  
Emanuele Canestrari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Quantitative Polymerase Chain Reaction ◽  
Disease Free Survival ◽  
Copy Number Gain ◽  
Free Survival ◽  
Prognostic Effect ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

Purpose To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF. Patients and Methods A single-institution cohort of 230 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction. Quantitative polymerase chain reaction (qPCR) for MET CNG and sequencing for HGF DATE truncation (< 25 deoxyadenosines instead of 30) were used. Results were analyzed for association with disease-free survival (DFS) and overall survival (OS). To assess the reliability of the qPCR measurement, a random sample of cases was reanalyzed using an alternative assay (fluorescent in situ hybridization [FISH]) with calculation of the intracorrelation coefficient (ICC). Results In 216 assessable patients, MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients (10%) and 30 patients (13%), respectively. Patients with MET CNG five or more copies (MET-positive) showed significantly worse prognosis with multivariate hazard ratio (HR) of 3.02 (95% CI, 1.71 to 5.33; P < .001) for DFS and multivariate HR of 2.91 (95% CI, 1.65 to 5.11; P < .001) for OS. The agreement between qPCR and FISH was high, with ICC = 0.9% (95% CI, 0.81% to 0.95%; the closer the ICC is to 1, the greater is the agreement). HGF-truncated DATE did not show relevant prognostic effect. Conclusion In this study, qPCR revealed approximately 10% of white patients with gastric cancer harboring MET CNG of five or more copies. This marker was significantly associated with unfavorable prognosis. This information is relevant to the current clinical development of anti-MET compounds.

scholarly journals Automated Extraction of DNA and RNA from a Single Formalin-Fixed Paraffin-Embedded Tissue Section for Analysis of Both Single-Nucleotide Polymorphisms and mRNA Expression

2010 ◽  
Vol 56 (12) ◽  
pp. 1845-1853 ◽  
Author(s):  
Guido Hennig ◽  
Mathias Gehrmann ◽  
Udo Stropp ◽  
Hiltrud Brauch ◽  
Peter Fritz ◽  
...  
Keyword(s):  
Extraction Method ◽  
Nucleotide Polymorphisms ◽  
Automated Extraction ◽  
Single Nucleotide ◽  
Normal Tissues ◽  
Dna And Rna ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Rna And Dna ◽  
Formalin Fixed

BACKGROUND There is an increasing need for the identification of both DNA and RNA biomarkers from pathodiagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples for the exploration of individualized therapy strategies in cancer. We investigated a fully automated, xylene-free nucleic acid extraction method for the simultaneous analysis of RNA and DNA biomarkers related to breast cancer. METHODS We copurified both RNA and DNA from a single 10-μm section of 210 paired samples of FFPE tumor and adjacent normal tissues (1–25 years of archival time) using a fully automated extraction method. Half of the eluate was DNase I digested for mRNA expression analysis performed by using reverse-transcription quantitative PCR for the genes estrogen receptor 1 (ESR1), progesterone receptor (PGR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) (ERBB2), epoxide hydrolase 1 (EPHX1), baculoviral IAP repeat-containing 5 (BIRC5), matrix metallopeptidase 7 (MMP7), vascular endothelial growth factor A (VEGFA), and topoisomerase (DNA) II alpha 170kDa (TOP2A). The remaining undigested aliquot was used for the analysis of 7 single-nucleotide polymorphisms (SNPs) by MALDI-TOF mass spectrometry. RESULTS In 208 of 210 samples (99.0%) the protocol yielded robust quantification-cycle values for both RNA and DNA normalization. Expression of the 8 breast cancer genes was detected in 81%–100% of tumor tissues and 21%–100% of normal tissues. The 7 SNPs were successfully genotyped in 91%–97% of tumor and 94%–97% of normal tissues. Allele concordance between tumor and normal tissue was 98.9%–99.5%. CONCLUSIONS This fully automated process allowed an efficient simultaneous extraction of both RNA and DNA from a single FFPE section and subsequent dual analysis of selected genes. High gene expression and genotyping detection rates demonstrate the feasibility of molecular profiling from limited archival patient samples.

A 2-Protein Signature Predicting Clinical Outcome in High-Grade Serous Ovarian Cancer

2018 ◽  
Vol 28 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Chengjuan Jin ◽  
Yingfeng Xue ◽  
Yingwei Li ◽  
Hualei Bu ◽  
Hongfeng Yu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Subtypes ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Multivariate Regression Analysis ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Free Survival ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

ObjectiveHigh-grade serous ovarian cancer (HGSOC) accounts for approximately 70% deaths in ovarian cancer. The overall survival (OS) of HGSOC is poor and still remains a clinical challenge. High-grade serous ovarian cancer can be divided into 4 molecular subtypes. The prognosis of different molecular subtypes is still unclear. We aimed to investigate the prognostic values of immunohistochemistry-based different molecular subtypes in patients with HGSOC.MethodsWe analyzed the protein expression of representative biomarkers (CXCL11, HMGA2, and MUC16) of 3 different molecular subtypes in 110 formalin-fixed, paraffin-embedded HGSOC by tissue microarrays.ResultsHigh CXCL11 expression predicted worse OS, not disease-free survival (DFS; P = 0.028 for OS, P = 0.191 for DFS). High HMGA2 expression predicted worse OS and DFS (P = 0.037 for OS, P = 0.021 for DFS). MUC16 expression was not associated with OS or DFS (P = 0.919 for OS, P = 0.517 for DFS). Multivariate regression analysis showed that CXCL11 combined with HMGA2 signature was an independent predictor for OS and DFS in patients with HGSOC.ConclusionsCXCL11 combined with HMGA2 signature was a clinically applicable prognostic model that could precisely predict an HGSOC patient's OS and tumor recurrence. This model could serve as an important tool for risk assessment of HGSOC prognosis.

Association of single nucleotide polymorphisms (SNPs) in SULT1E1 with response to treatment with abiraterone acetate (AA) in men with metastatic castration refractory prostate cancer (mCRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 222-222
Author(s):  
Tyler Howard Buckley ◽  
Anitha Alex ◽  
James M. Farnham ◽  
David Gill ◽  
Shiven B. Patel ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Gleason Score ◽  
Multiple Testing ◽  
Genetic Model ◽  
Hazard Analysis ◽  
Predictive Biomarkers ◽  
Abiraterone Acetate ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

222 Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict response to AA in men with mCRPC, serve as prognostic and predictive biomarkers, and guide towards more individualized therapy. Methods: 836 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 61 genes reported to be involved in the androgen metabolic pathway were investigated for association with time to treatment failure (TTF) in 68 Caucasian men with mCRPC undergoing treatment with AA. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Three SNPs in SULT1E1 were associated with TTF on AA therapy after correcting for multiple testing (p < .00007) while controlling for Gleason Score (Table). Conclusions: SNPs in SULT1E1(estrogen sulfotransferase gene) were significantly associated with TTF on AA therapy, and may serve as predictive markers to treatment with AA. Further validation is being performed in a larger cohort of men with mCRPC. [Table: see text]

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