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Predictive value of...
Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer
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- Olah, Csilla (author)
- University of Duisburg-Essen
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- Reis, Henning (author)
- University Hospital Frankfurt
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- Hoffmann, Michèle J. (author)
- University Hospital of Düsseldorf
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- Mairinger, Fabian (author)
- University of Duisburg-Essen
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- Ting, Saskia (author)
- University of Duisburg-Essen
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- Hadaschik, Boris (author)
- University of Duisburg-Essen
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- Krafft, Ulrich (author)
- University of Duisburg-Essen
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- Grünwald, Viktor (author)
- University of Duisburg-Essen
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- Nyirady, Peter (author)
- Semmelweis University
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- Varadi, Melinda (author)
- Semmelweis University
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- Győrffy, Balázs (author)
- Semmelweis University
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- Kiss, Andras (author)
- Semmelweis University
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- Szekely, Eszter (author)
- Semmelweis University
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- Sjödahl, Gottfrid (author)
- Lund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,Genomiska analyser av urinblåscancer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urinblåsecancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Urology - urothelial cancer, Malmö,Lund University Research Groups,Urothelial Cancer Genomics,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Urothelial cancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Szarvas, Tibor (author)
- University of Duisburg-Essen
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(creator_code:org_t)
- 2022-10-07
- 2023
- English.
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In: Cancer Medicine. - : Wiley. - 2045-7634. ; 12:5, s. 5222-5232
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Abstract
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- Objective: Although targeted approaches have become available in second- and third-line settings, platinum-based chemotherapy remains the standard first-line treatment for advanced muscle-invasive bladder cancer (MIBC). Therefore, the prediction of platinum resistance is of utmost clinical importance. Methods: In this study, we established a routine compatible method for the molecular classification of MIBC samples according to various classification systems and applied this method to evaluate the impact of subtypes on survival after adjuvant chemotherapy. This retrospective study included 191 patients with advanced MIBC (pT≥3 or pN+) who underwent radical cystectomy, with or without adjuvant chemotherapy. A 48-gene panel and classifier rule set were established to determine molecular subtypes according to TCGA, MDA, LundTax, and Consensus classifications. Additionally, 12 single platinum-predictive candidate genes were assessed. The results were correlated with patients' clinicopathological and follow-up data and were validated using independent data sets. Results: Our final evaluation of 159 patients demonstrated better survival in the luminal groups for those who received chemotherapy compared with those who did not. In contrast, no such differences were observed in basal subtypes. The use of chemotherapy was associated with better survival in patients with high APOBEC3G expression (p < 0.002). This association was confirmed using an independent data set of patients who received neoadjuvant platinum therapy. Conclusions: The proposed method robustly replicates the most commonly used transcriptome-based subtype classifications from paraffin-embedded tissue samples. The luminal, but not basal, molecular subtypes had the greatest benefit from adjuvant platinum therapy. We identified and validated APOBEC3G as a novel predictive marker for platinum-treated patients.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Keyword
- APOBEC3G
- bladder cancer
- cisplatin
- molecular subtype classification
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Olah, Csilla
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Reis, Henning
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Hoffmann, Michèl ...
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Mairinger, Fabia ...
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Ting, Saskia
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Hadaschik, Boris
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show more...
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Krafft, Ulrich
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Grünwald, Viktor
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Nyirady, Peter
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Varadi, Melinda
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Győrffy, Balázs
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Kiss, Andras
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Szekely, Eszter
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Sjödahl, Gottfri ...
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Szarvas, Tibor
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Urology and Neph ...
- Articles in the publication
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Cancer Medicine
- By the university
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Lund University