Supplementary Material for: Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer

Handle URI:
http://hdl.handle.net/10754/624134
Title:
Supplementary Material for: Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer
Authors:
Roperch, Jean-Pierre; Grandchamp, Bernard; Desgrandchamps, François; Mongiat-Artus, Pierre; Ravery, Vincent; Ouzaid, Idir; Roupret, Morgan; Phe, Véronique; Ciofu, Calin; Tubach, Florence; Cussenot, Olivier; Incitti, Roberto
Abstract:
Abstract Background Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. Methods We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time’s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. Results For Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers’ methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. Conclusions We showed that combined analysis of FGFR3 mutation and DNA methylation markers on urine can be a useful strategy in diagnosis, surveillance and for risk stratification of patients with NMIBC. These results provide the basis for a highly accurate noninvasive test for population screening and allowing to decrease the frequency of cystoscopy, an important feature for both patient quality of life improvement and care cost reduction.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Roperch, J.-P., Grandchamp, B., Desgrandchamps, F., Mongiat-Artus, P., Ravery, V., Idir Ouzaid, … Incitti, R. (2016). Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer. Figshare. https://doi.org/10.6084/m9.figshare.c.3619151
Publisher:
Figshare
Issue Date:
2016
DOI:
10.6084/m9.figshare.c.3619151
Type:
Dataset
Is Supplement To:
Roperch J-P, Grandchamp B, Desgrandchamps F, Mongiat-Artus P, Ravery V, et al. (2016) Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer. BMC Cancer 16. Available: http://dx.doi.org/10.1186/s12885-016-2748-5.; DOI:10.1186/s12885-016-2748-5; HANDLE:http://hdl.handle.net/10754/621987
Appears in Collections:
Computational Bioscience Research Center (CBRC); Datasets

Full metadata record

DC FieldValue Language
dc.contributor.authorRoperch, Jean-Pierreen
dc.contributor.authorGrandchamp, Bernarden
dc.contributor.authorDesgrandchamps, Françoisen
dc.contributor.authorMongiat-Artus, Pierreen
dc.contributor.authorRavery, Vincenten
dc.contributor.authorOuzaid, Idiren
dc.contributor.authorRoupret, Morganen
dc.contributor.authorPhe, Véroniqueen
dc.contributor.authorCiofu, Calinen
dc.contributor.authorTubach, Florenceen
dc.contributor.authorCussenot, Olivieren
dc.contributor.authorIncitti, Robertoen
dc.date.accessioned2017-06-06T07:44:32Z-
dc.date.available2017-06-06T07:44:32Z-
dc.date.created2016-12-15en
dc.date.issued2016en
dc.identifier.citationRoperch, J.-P., Grandchamp, B., Desgrandchamps, F., Mongiat-Artus, P., Ravery, V., Idir Ouzaid, … Incitti, R. (2016). Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer. Figshare. https://doi.org/10.6084/m9.figshare.c.3619151en
dc.identifier.doi10.6084/m9.figshare.c.3619151en
dc.identifier.urihttp://hdl.handle.net/10754/624134-
dc.description.abstractAbstract Background Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. Methods We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time’s and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. Results For Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers’ methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. Conclusions We showed that combined analysis of FGFR3 mutation and DNA methylation markers on urine can be a useful strategy in diagnosis, surveillance and for risk stratification of patients with NMIBC. These results provide the basis for a highly accurate noninvasive test for population screening and allowing to decrease the frequency of cystoscopy, an important feature for both patient quality of life improvement and care cost reduction.en
dc.publisherFigshareen
dc.rightsCC BYen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectMedicineen
dc.subjectCell Biologyen
dc.subjectGeneticsen
dc.subjectMolecular Biologyen
dc.subjectBiotechnologyen
dc.subjectCanceren
dc.subjectInfectious Diseasesen
dc.titleSupplementary Material for: Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder canceren
dc.typeDataseten
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
kaust.authorIncitti, Robertoen
dc.type.resourceCollectionen
dc.relation.isSupplementToRoperch J-P, Grandchamp B, Desgrandchamps F, Mongiat-Artus P, Ravery V, et al. (2016) Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer. BMC Cancer 16. Available: http://dx.doi.org/10.1186/s12885-016-2748-5.en
dc.relation.isSupplementToDOI:10.1186/s12885-016-2748-5en
dc.relation.isSupplementToHANDLE:http://hdl.handle.net/10754/621987en
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