School of Medicine, University of Glasgow, Glasgow, UK.
Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
J Pathol Clin Res. 2020 Oct;6(4):283-296. doi: 10.1002/cjp2.171. Epub 2020 May 13.
Histological 'phenotypic subtypes' that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I-III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I-III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease-free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II-III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893-patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p < 0.001) in these patients. In a 146-patient external cohort, phenotypic subtype independently stratified patients by DFS (p = 0.028), validating their prognostic value. In 1343 SCOT trial patients, the effect of treatment type significantly depended on phenotypic subtype (p = 0.011). Phenotypic subtype independently associated with DFS in stage III patients receiving FOLFOX (p = 0.028). Furthermore, the immune subtype significantly associated with better response to FOLFOX compared to CAPOX adjuvant chemotherapy in stage III patients (p = 0.013). In conclusion, histological phenotypic subtypes are an effective prognostic classification in patients with stage III CRC that associates with risk of recurrence and response to FOLFOX adjuvant chemotherapy.
组织学“表型亚型”将患者分为四组（免疫型、经典型、潜伏型和基质型），此前已在 I-III 期结直肠癌（CRC）试验队列中证明可对生存进行分层。然而，其临床实用性尚未得到验证。因此，本研究在其他患者队列中评估了这些亚型的预后价值，并探讨了其与复发风险和对化疗反应的关系。本研究使用了两个独立的 I-III 期 CRC 患者队列（内部队列和外部队列）来研究表型亚型。主要终点是无病生存期（DFS），次要终点是复发风险（RR）。SCOT 辅助化疗试验中的 II-III 期患者被用于进一步验证预后价值，并进行探索性分析，以评估与辅助化疗的关系。在一个 893 例患者的内部队列中，表型亚型与 DFS 独立相关（p = 0.025），在 III 期患者中则减弱（p = 0.020）。表型亚型还与这些患者的 RR 独立相关（p < 0.001）。在一个 146 例患者的外部队列中，表型亚型独立地对 DFS 进行了分层（p = 0.028），验证了其预后价值。在 1343 例 SCOT 试验患者中，治疗类型的效果显著依赖于表型亚型（p = 0.011）。在接受 FOLFOX 治疗的 III 期患者中，表型亚型与 DFS 独立相关（p = 0.028）。此外，在 III 期患者中，与 CAPOX 辅助化疗相比，免疫型与 FOLFOX 辅助化疗的更好反应显著相关（p = 0.013）。总之，组织学表型亚型是 III 期 CRC 患者的一种有效的预后分类方法，与复发风险和对 FOLFOX 辅助化疗的反应相关。
