Abstract Background The recently identified classical and basal-like molecular subtypes of pancreatic cancer impact on overall survival (OS). However, the added value of routine subtyping in both clinical practice and randomized trials is still unclear, as most studies do not consider clinicopathological parameters. This study examined the clinical prognostic value of molecular subtyping in patients with resected pancreatic cancer. Methods Subtypes were determined on fresh-frozen resected pancreatic cancer samples from three Dutch centres using the Purity Independent Subtyping of Tumours classification. Patient, treatment, and histopathological variables were compared between subtypes. The prognostic value of subtyping in (simulated) pre- and postoperative settings was assessed using Kaplan–Meier and Cox regression analyses. Results Of 199 patients with resected pancreatic cancer, 164 (82.4 per cent) were classified as the classical and 35 (17.6 per cent) as the basal-like subtype. Patients with a basal-like subtype had worse OS (11 versus 16 months (HR 1.49, 95 per cent c.i. 1.03 to 2.15; P = 0.035)) than patients with a classical subtype. In multivariable Cox regression analysis, including only clinical variables, the basal-like subtype was a statistically significant predictor for poor OS (HR 1.61, 95 per cent c.i. 1.11 to 2.34; P = 0.013). When histopathological variables were added to this model, the prognostic value of subtyping decreased (HR 1.49, 95 per cent c.i. 1.01 to 2.19; P = 0.045). Conclusion The basal-like subtype was associated with worse OS in patients with resected pancreatic cancer. Adding molecular classification to inform on tumor biology may be used in patient stratification.

中文翻译：

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SPACIOUS-2 多中心研究中经典和基底样分子亚型对切除胰腺癌总体生存率的影响

摘要 背景最近发现的胰腺癌经典分子亚型和基础样分子亚型对总生存期 (OS) 产生影响。然而，常规亚型分型在临床实践和随机试验中的附加值仍不清楚，因为大多数研究不考虑临床病理参数。本研究探讨了分子分型对切除胰腺癌患者的临床预后价值。 方法使用肿瘤纯度独立亚型分类对来自三个荷兰中心的新鲜冷冻切除胰腺癌样本进行亚型确定。对亚型之间的患者、治疗和组织病理学变量进行比较。使用 Kaplan-Meier 和 Cox 回归分析评估（模拟）术前和术后设置中亚型的预后价值。 结果在 199 名切除胰腺癌的患者中，164 名（82.4%）被归类为经典亚型，35 名（17.6%）被归类为基底样亚型。与经典亚型患者相比，基础样亚型患者的 OS 较差（11 个月与 16 个月（HR 1.49，95% CI 1.03 至 2.15；P = 0.035））。在仅包括临床变量的多变量 Cox 回归分析中，基底样亚型是 OS 较差的统计显着预测因子（HR 1.61，95% CI 1.11 至 2.34；P = 0.013）。当将组织病理学变量添加到该模型中时，亚型分型的预后价值下降（HR 1.49，95% CI 1.01 至 2.19；P = 0.045）。 结论基底样亚型与切除胰腺癌患者的 OS 较差相关。添加分子分类以了解肿瘤生物学可用于患者分层。