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.MethodsIn
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.ResultsOur
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.ConclusionsThe
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.
