Basal/squamous and mixed subtype bladder cancers present poor outcomes after neoadjuvant chemotherapy in the VESPER trial.

Gene expression-based subtypes may serve as biomarkers, though which subtypes will respond, notably when it comes to the basal subtype, remains contentious.

基于基因表达的亚型可能作为生物标志物，尽管哪些亚型会响应，特别是当涉及到基底亚型时，仍然存在争议。

patients_and_methods

This post hoc study analyzed 300 NAC-treated patients enrolled in the GETUG/AFU VESPER trial, with transurethral diagnostic formalin-fixed paraffin-embedded tissue which underwent pathological review before being sequenced. 'Mixed' subtype was defined for tumors displaying at least two different Consensus molecular subtypes in separate regions.

这项事后研究分析了在GETUG/AFU VESPER试验中接受新辅助化疗(NAC)治疗的300名患者，这些患者的经尿道诊断的组织标本经过病理复审后进行了测序。'混合'亚型被定义为在不同区域显示出至少两种不同共识分子亚型的肿瘤。

We evaluated the association between molecular subtypes and outcome after NAC.

我们评估了分子亚型与新辅助化疗(NAC)后结果之间的关联。

Tumors with remaining tissue at cystectomy (n = 83) were compared with pre-treatment tumors.

在膀胱切除术中剩余组织的肿瘤（n = 83）与治疗前的肿瘤进行了比较。

Results

Cases were classified basal/squamous (Ba/Sq) (n = 84), luminal unstable (n = 57), stroma-rich (n = 53), mixed (n = 48), luminal papillary (n = 39), luminal non-specific (n = 18), and neuroendocrine-like (n = 1), with 30/48 mixed cases including a Ba/Sq component.

病例被分类为基底/鳞状（Ba/Sq）（n = 84），不稳定型腔内（n = 57），富含基质（n = 53），混合型（n = 48），腔内乳头状（n = 39），腔内非特异性（n = 18），以及类神经内分泌型（n = 1），其中30/48的混合型病例包含有Ba/Sq成分。

Compared with other molecular subtypes in a multivariate Cox model, Ba/Sq (pure or mixed) patients had an increased hazard ratio(HR) of progression-free survival[HR 2.0, 95% confidence interval(CI) 1.36-3.0].

在多变量Cox模型中与其他分子亚型比较，Ba/Sq（纯或混合）患者的无进展生存期风险比（HR）增加[HR 2.0, 95%置信区间（CI）1.36-3.0]。

Mixed tumors were associated with decreased metabolic activity that could account for chemoresistance.

混合肿瘤与代谢活性降低有关，这可以解释化疗耐药性。

Ba/Sq and mixed non-responders mostly maintained their subtype at cystectomy and have fewer myeloid dendritic cells after NAC.

Ba/Sq 和混合非反应者在膀胱切除术后大多保持了其亚型，并且在接受新辅助化疗(NAC)后，其髓样树突状细胞数量减少。

Tumors classified luminal papillary at transurethral resection of the urinary bladder tumor exhibited an increase in T CD4+ and macrophage signatures after NAC.

在经尿道膀胱肿瘤切除术中被分类为乳头状腔内的肿瘤，在接受新辅助化疗(NAC)后，T CD4+和巨噬细胞标志物有所增加。

Other subtypes did not show significant immune changes after NAC.

其他亚型在接受新辅助化疗(NAC)后未显示出显著的免疫变化。

Our study design relied on detailed pathological review, which precluded evaluating the mixed subtype in published datasets.

我们的研究设计依赖于详细的病理学审查，这限制了我们对已发表数据集中混合亚型的评估。

Furthermore, the sample size for post-NAC analyses constrained the statistical power of these findings.

此外，用于术后新辅助化疗（NAC）分析的样本量限制了这些发现的统计功效。

Conclusions

Our findings underscore the importance of recognizing intra-tumor heterogeneity in MIBC and its role in chemoresistance associated with Ba/Sq subtype, and provide valuable insights that could help future treatment development and improve patient outcomes.

我们的发现强调了认识膀胱尿路上皮癌（MIBC）肿瘤内异质性的重要性，以及其在Ba/Sq亚型相关化疗耐药性中的作用，并提供了宝贵的见解，这些见解可能有助于未来治疗开发并改善患者预后。