Abstract

BACKGROUND:

Bladder cancers have high total mutation burdens resulting in genomic diversity and intra- and inter-tumor heterogeneity that may impact the diversity of gene expression, biologic aggressiveness, and potentially response to therapy. To compare bladder cancers among patients, an organizational structure is necessary that describes the tumor at the histologic and molecular level. These “molecular subtypes”, or “expression subtypes” of bladder cancer were originally described in 2010 and continue to evolve secondary to next generation sequencing (NGS) and an increasing public repository of well-annotated cohorts.

OBJECTIVE:

To review the history and methodology of expression-based subtyping of non-muscle invasive (NMIBC) and muscle invasive bladder cancer (MIBC).

METHODS:

A literature review was performed of primary papers from PubMed that described subtyping methods and their descriptive feature including search terms of “subtype”, and “bladder cancer”.

RESULTS:

21 papers were identified for review. Tumor subtyping developed from N = 2 to N = 6 subtyping schemes with most subtypes comprised of at least luminal and basal tumors. Most NMIBCs are luminal cancers and luminal MIBCs may be associated with less aggressive features, while one study of basal tumors identified a better clinical outcome with systemic chemotherapy. Tumors with a 53-like signature may have intrinsic resistance to chemotherapy. The heterogeneity of tumors, which is likely derived from stromal components and immune cell infiltration, affect subtype calls.

CONCLUSION:

Subtyping, while still evolving, is ready for testing in clinical trials. Improved patient selection with tumor subtyping may help with tumor classification and potentially match patient or tumor to therapy.

中文翻译：

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肿瘤分型：以治疗为目标，了解异质性

摘要

背景：

膀胱癌具有高的总突变负担，导致基因组多样性以及肿瘤内和肿瘤间异质性，这可能会影响基因表达的多样性，生物学攻击性以及对治疗的潜在反应。为了比较患者之间的膀胱癌，有必要在组织学和分子水平上描述肿瘤的组织结构。膀胱癌的这些“分子亚型”或“表达亚型”最初于2010年进行了描述，并继第二代测序（NGS）和注释明确的人群越来越多的公共资料库之后继续发展。

目的：

回顾非肌肉浸润性（NMIBC）和肌肉浸润性膀胱癌（MIBC）基于表达的亚型的历史和方法。

方法：

对PubMed的主要论文进行了文献综述，描述了分型方法及其描述性特征，包括“亚型”和“膀胱癌”的搜索词。

结果：

确定了21篇论文进行审查。肿瘤亚型从N = 2发展到N = 6亚型方案，大多数亚型至少由管腔和基底肿瘤组成。大多数NMIBC是管腔癌，管腔MIBC可能具有较弱的侵袭性特征，而一项针对基础肿瘤的研究则发现全身化疗具有更好的临床效果。具有53样特征的肿瘤可能对化学疗法具有内在抗性。肿瘤的异质性很可能源自基质成分和免疫细胞浸润，影响亚型。

结论：

亚型虽然仍在发展，但已准备好在临床试验中进行测试。通过肿瘤亚型改善患者选择可能有助于肿瘤分类，并可能使患者或肿瘤与治疗相匹配。