Department of Epidemiology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.
Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, The Netherlands.
J Cancer Res Clin Oncol. 2023 Aug;149(9):6271-6282. doi: 10.1007/s00432-023-04581-w. Epub 2023 Feb 1.
Tumor location and tumor node metastasis (TNM) stage guide treatment decisions in colorectal cancer (CRC) patients. However, patients with the same disease stage do not benefit equally from adjuvant therapy. Hence, there remains an urgent clinical need to identify prognostic and/or predictive biomarker(s) to personalize treatment decisions. In this exploratory study, we investigated whether our previously defined metabolic Warburg-subtypes can predict which CRC patients might derive survival benefit from adjuvant therapy.
Information regarding treatment (surgery only: n = 1451; adjuvant radiotherapy: n = 82; or adjuvant chemotherapy: n = 260) and Warburg-subtype (Warburg-low: n = 485, -moderate: n = 641, or -high: n = 667) was available for 1793 CRC patients from the Netherlands Cohort Study (NLCS). Kaplan-Meier curves and Cox regression models were used to investigate survival benefit from adjuvant therapy compared to surgery-only for the different Warburg-subtypes.
Patients with Warburg-moderate CRC (HR 0.64; 95% CI 0.47-0.86, HR 0.61; 95% CI 0.47-0.80), and possibly Warburg-high CRC (HR 0.86; 95% CI 0.65-1.14, HR 0.82; 95% CI 0.64-1.05), had survival benefit from adjuvant therapy. No survival benefit was observed for patients with Warburg-low CRC (HR 1.07; 95% CI 0.76-1.52, HR 0.95; 95% CI 0.70-1.30). There was a significant interaction between Warburg-subtype and adjuvant therapy for CRC-specific survival (p = 0.049) and overall survival (p = 0.035).
Our results suggest that Warburg-subtypes may predict survival benefit from adjuvant therapy in CRC patients. A survival benefit from adjuvant therapy was observed for patients with Warburg-moderate and possibly Warburg-high CRC, but not for patients with Warburg-low CRC. Future prospective studies are necessary to validate our findings.
肿瘤位置和肿瘤淋巴结转移（TNM）分期指导结直肠癌（CRC）患者的治疗决策。然而，具有相同疾病分期的患者并不平等受益于辅助治疗。因此，迫切需要确定预后和/或预测生物标志物，以实现治疗决策的个体化。在这项探索性研究中，我们调查了之前定义的代谢沃伯格亚型是否可以预测哪些 CRC 患者可能从辅助治疗中获益。
我们获得了来自荷兰队列研究（NLCS）的 1793 例 CRC 患者的治疗（仅手术：n=1451；辅助放疗：n=82；或辅助化疗：n=260）和沃伯格亚型（沃伯格低：n=485，-中度：n=641，或-高：n=667）的信息。使用 Kaplan-Meier 曲线和 Cox 回归模型来研究不同沃伯格亚型的辅助治疗相对于仅手术的生存获益。
具有沃伯格中度 CRC（HR 0.64；95%CI 0.47-0.86，HR 0.61；95%CI 0.47-0.80）和可能的沃伯格高度 CRC（HR 0.86；95%CI 0.65-1.14，HR 0.82；95%CI 0.64-1.05）的患者从辅助治疗中获益。具有沃伯格低度 CRC（HR 1.07；95%CI 0.76-1.52，HR 0.95；95%CI 0.70-1.30）的患者未观察到生存获益。在 CRC 特异性生存（p=0.049）和总生存（p=0.035）方面，沃伯格亚型和辅助治疗之间存在显著的交互作用。
我们的结果表明，沃伯格亚型可能预测 CRC 患者从辅助治疗中获益。在沃伯格中度和可能的沃伯格高度 CRC 患者中观察到辅助治疗的生存获益，但在沃伯格低度 CRC 患者中未观察到。需要前瞻性研究来验证我们的发现。
