Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer
Abstract 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 i...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.5324 |
| _version_ | 1797866843961032704 |
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| author | Csilla Olah Henning Reis Michèle J. Hoffmann Fabian Mairinger Saskia Ting Boris Hadaschik Ulrich Krafft Viktor Grünwald Peter Nyirady Melinda Varadi Balázs Győrffy Andras Kiss Eszter Szekely Gottfrid Sjödahl Tibor Szarvas |
| author_facet | Csilla Olah Henning Reis Michèle J. Hoffmann Fabian Mairinger Saskia Ting Boris Hadaschik Ulrich Krafft Viktor Grünwald Peter Nyirady Melinda Varadi Balázs Győrffy Andras Kiss Eszter Szekely Gottfrid Sjödahl Tibor Szarvas |
| author_sort | Csilla Olah |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T23:31:53Z |
| format | Article |
| id | doaj.art-7547c69a833c47a98b4d560264ca3735 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-09T23:31:53Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-7547c69a833c47a98b4d560264ca37352023-03-21T05:20:40ZengWileyCancer Medicine2045-76342023-03-011255222523210.1002/cam4.5324Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancerCsilla Olah0Henning Reis1Michèle J. Hoffmann2Fabian Mairinger3Saskia Ting4Boris Hadaschik5Ulrich Krafft6Viktor Grünwald7Peter Nyirady8Melinda Varadi9Balázs Győrffy10Andras Kiss11Eszter Szekely12Gottfrid Sjödahl13Tibor Szarvas14Department of Urology University of Duisburg‐Essen Essen GermanyDr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt Frankfurt am Main GermanyDepartment of Urology Medical Faculty and University Hospital Düsseldorf, Heinrich‐Heine‐University Düsseldorf Düsseldorf GermanyInstitute of Pathology, University Medicine Essen, University of Duisburg‐Essen Essen GermanyInstitute of Pathology, University Medicine Essen, University of Duisburg‐Essen Essen GermanyDepartment of Urology University of Duisburg‐Essen Essen GermanyDepartment of Urology University of Duisburg‐Essen Essen GermanyDepartment of Medical Oncology University of Duisburg‐Essen Essen GermanyDepartment of Urology Semmelweis University Budapest HungaryDepartment of Urology Semmelweis University Budapest HungaryResearch Centre for Natural Sciences, Cancer Biomarker Research Group Institute of Enzymology Budapest Hungary2nd Department of Pathology Semmelweis University Budapest Hungary2nd Department of Pathology Semmelweis University Budapest HungaryDepartment of Translational Medicine Lund University Lund SwedenDepartment of Urology University of Duisburg‐Essen Essen GermanyAbstract 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.https://doi.org/10.1002/cam4.5324APOBEC3Gbladder cancercisplatinmolecular subtype classification |
| spellingShingle | Csilla Olah Henning Reis Michèle J. Hoffmann Fabian Mairinger Saskia Ting Boris Hadaschik Ulrich Krafft Viktor Grünwald Peter Nyirady Melinda Varadi Balázs Győrffy Andras Kiss Eszter Szekely Gottfrid Sjödahl Tibor Szarvas Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer Cancer Medicine APOBEC3G bladder cancer cisplatin molecular subtype classification |
| title | Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer |
| title_full | Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer |
| title_fullStr | Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer |
| title_full_unstemmed | Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer |
| title_short | Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer |
| title_sort | predictive value of molecular subtypes and apobec3g for adjuvant chemotherapy in urothelial bladder cancer |
| topic | APOBEC3G bladder cancer cisplatin molecular subtype classification |
| url | https://doi.org/10.1002/cam4.5324 |
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