Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer
(2023) In Cancer Medicine 12(5). p.5222-5232- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- APOBEC3G, bladder cancer, cisplatin, molecular subtype classification
- in
- Cancer Medicine
- volume
- 12
- issue
- 5
- pages
- 5222 - 5232
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:36204983
- scopus:85139405337
- ISSN
- 2045-7634
- DOI
- 10.1002/cam4.5324
- language
- English
- LU publication?
- yes
- id
- f82ab630-2a53-4b2e-bfcb-b11720cde6cc
- date added to LUP
- 2022-12-19 15:05:49
- date last changed
- 2024-06-27 23:12:53
@article{f82ab630-2a53-4b2e-bfcb-b11720cde6cc,
abstract = {{<p>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.</p>}},
author = {{Olah, Csilla and Reis, Henning and Hoffmann, Michèle J. and Mairinger, Fabian and Ting, Saskia and Hadaschik, Boris and Krafft, Ulrich and Grünwald, Viktor and Nyirady, Peter and Varadi, Melinda and Győrffy, Balázs and Kiss, Andras and Szekely, Eszter and Sjödahl, Gottfrid and Szarvas, Tibor}},
issn = {{2045-7634}},
keywords = {{APOBEC3G; bladder cancer; cisplatin; molecular subtype classification}},
language = {{eng}},
number = {{5}},
pages = {{5222--5232}},
publisher = {{Wiley-Blackwell}},
series = {{Cancer Medicine}},
title = {{Predictive value of molecular subtypes and APOBEC3G for adjuvant chemotherapy in urothelial bladder cancer}},
url = {{http://dx.doi.org/10.1002/cam4.5324}},
doi = {{10.1002/cam4.5324}},
volume = {{12}},
year = {{2023}},
}