Prospective patient stratification into robust cancer-cell intrinsic subtypes from colorectal cancer biopsies.
Prospective patient stratification into robust cancer-cell intrinsic subtypes from colorectal cancer biopsies.
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DOI：
10.1002/path.5051
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Dunne PD
中科院分区：
文献类型：
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作者：
Alderdice M;Richman SD;Gollins S;Stewart JP;Hurt C;Adams R;McCorry AM;Roddy AC;Vimalachandran D;Isella C;Medico E;Maughan T;McArt DG;Lawler M;Dunne PD
结直肠癌（CRC）活检是准确诊断的基础，但在分子引导的临床试验中也与患者分层有关。共识分子亚型（cms）和结直肠癌固有亚型（CRISs）转录特征在改善预后/预测患者分配方面具有潜在的临床应用价值。然而，它们提供可靠分类的能力，特别是在多区域或不同时间点的预处理活检中，仍有待检验。在这项研究中，我们对CRC转录特征的稳健性进行了全面评估，包括CRIS和CMS，使用了一系列目前用于临床和转化研究的肿瘤采样方法。这些分析包括使用(i)激光捕获微解剖的结直肠癌组织，（ii） 8个公开的直肠癌活检数据集（n = 543）， （iii）系列活检（来自AXEBeam试验，NCT00828672, n = 10）， （iv）结肠肿瘤的多区域活检（n = 29个活检，n = 7个肿瘤），以及(v) ii期直肠癌试验COPERNCIUS （NCT01263171, n = 44）的预处理活检。与先前使用结直肠癌切除材料获得的结果相比，我们证明活检组织中的CMS分类可靠地分类患者亚型的能力显着降低（活检中未知的比例为43%，而切除中未知的比例为13%，p = 0.0001）。相比之下，使用CRIS分类器时，活检和切除的分类率无显著差异。此外，我们证明，与CMS相比，CRIS在CRC原发性肿瘤组织中提供了更好的空间和时间稳健的分子亚型分类（分别为p = 0.003和p = 0.02）。这些发现有可能为正在进行的基于活检的结直肠癌患者分层提供信息，从而使患者能够在前瞻性多组、多阶段临床试验中稳健、稳定地分配到临床信息组。©2018作者。由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版的病理学杂志。
Colorectal cancer (CRC) biopsies underpin accurate diagnosis, but are also relevant for patient stratification in molecularly‐guided clinical trials. The consensus molecular subtypes (CMSs) and colorectal cancer intrinsic subtypes (CRISs) transcriptional signatures have potential clinical utility for improving prognostic/predictive patient assignment. However, their ability to provide robust classification, particularly in pretreatment biopsies from multiple regions or at different time points, remains untested. In this study, we undertook a comprehensive assessment of the robustness of CRC transcriptional signatures, including CRIS and CMS, using a range of tumour sampling methodologies currently employed in clinical and translational research. These include analyses using (i) laser‐capture microdissected CRC tissue, (ii) eight publically available rectal cancer biopsy data sets (n = 543), (iii) serial biopsies (from AXEBeam trial, NCT00828672; n = 10), (iv) multi‐regional biopsies from colon tumours (n = 29 biopsies, n = 7 tumours), and (v) pretreatment biopsies from the phase II rectal cancer trial COPERNCIUS (NCT01263171; n = 44). Compared to previous results obtained using CRC resection material, we demonstrate that CMS classification in biopsy tissue is significantly less capable of reliably classifying patient subtype (43% unknown in biopsy versus 13% unknown in resections, p = 0.0001). In contrast, there was no significant difference in classification rate between biopsies and resections when using the CRIS classifier. Additionally, we demonstrated that CRIS provides significantly better spatially‐ and temporally‐ robust classification of molecular subtypes in CRC primary tumour tissue compared to CMS (p = 0.003 and p = 0.02, respectively). These findings have potential to inform ongoing biopsy‐based patient stratification in CRC, enabling robust and stable assignment of patients into clinically‐informative arms of prospective multi‐arm, multi‐stage clinical trials. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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