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Circulating metabolites as a concept beyond tumor biology determining disease recurrence after resection of colorectal liver metastasis
HPB ( IF 2.9 ) Pub Date : 2021-06-24 , DOI: 10.1016/j.hpb.2021.06.415
Jan P Jonas 1 , Hubert Hackl 2 , David Pereyra 3 , Jonas Santol 3 , Gregor Ortmayr 3 , Benedikt Rumpf 3 , Sina Najarnia 3 , Dominic Schauer 4 , Christine Brostjan 3 , Thomas Gruenberger 5 , Patrick Starlinger 6
Affiliation  

Background

Micro-metastatic growth is considered the main source of early cancer recurrence. Nutritional and microenvironmental components are increasingly recognized to play a significant role in the liver. We explored the predictive potential of preoperative plasma metabolites for postoperative disease recurrence in colorectal cancer liver metastasis (CRCLM) patients.

Methods

All included patients (n = 71) had undergone R0 liver resection for colorectal cancer liver metastasis in the years between 2012 and 2018. Preoperative blood samples were collected and assessed for 180 metabolites using a preconfigured mass-spectrometry kit (Biocrates Absolute IDQ p180 kit). Postoperative disease-free (DFS) and overall survival (OS) were prospectively recorded. Patients that recurred within 6 months after surgery were defined as “high-risk” and, subsequently, a three-metabolite model was created which can assess DFS in our collective.

Results

Multiple lysophosphatidylcholines (lysoPCs) and phosphatidylcholines (PCs) significantly predicted disease recurrence within 6 months (strongest: PC aa C36:1 AUC = 0.83, p = 0.003, PC ae C34:0 AUC = 0.83, p = 0.004 and lysoPC a C18:1 AUC = 0.8, p = 0.006). High-risk patients had a median DFS of 183 days versus 522 days in low-risk population (p = 0.016, HR = 1.98 95% CI 1.16–4.35) with a 6 months recurrence rate of 47.6% versus 4.7%, outperforming routine predictors of oncological outcome.

Conclusion

Circulating metabolites identified CRCLM patients at highest risk for 6 months disease recurrence after surgery. Our data also suggests that circulating metabolites might play a significant pathophysiological role in micro-metastatic growth and concomitant early tumor recurrences after liver resection. However, the clinical applicability and performance of this proposed metabolomic concept needs to be independently validated in future studies.



中文翻译:

循环代谢物作为超越肿瘤生物学的概念确定结直肠肝转移切除术后疾病复发

背景

微转移生长被认为是早期癌症复发的主要来源。越来越多的人认识到营养和微环境成分在肝脏中发挥着重要作用。我们探讨了术前血浆代谢物对结直肠癌肝转移 (CRCLM) 患者术后疾病复发的预测潜力。

方法

所有纳入的患者(n = 71)在 2012 年至 2018 年期间因结直肠癌肝转移接受了 R0 肝切除术。收集术前血样并使用预配置的质谱试剂盒(Biocrates Absolute IDQ p180 试剂盒)评估 180 种代谢物. 前瞻性记录术后无病生存期(DFS)和总生存期(OS)。手术后 6 个月内复发的患者被定义为“高风险”,随后创建了一个三代谢物模型,可以评估我们集体的 DFS。

结果

多种溶血磷脂酰胆碱 (lysoPCs) 和磷脂酰胆碱 (PCs) 可显着预测 6 个月内的疾病复发(最强:PC aa C36:1 AUC = 0.83,p = 0.003,PC ae C34:0 AUC = 0.83,p = 0.004 和 lysoPC a C18: 1 AUC = 0.8,p = 0.006)。高风险患者的中位 DFS 为 183 天,而低风险人群为 522 天(p = 0.016,HR = 1.98 95% CI 1.16-4.35),6 个月复发率分别为 47.6% 和 4.7%,优于常规预测指标肿瘤学结果。

结论

循环代谢物鉴定出术后 6 个月疾病复发风险最高的 CRCLM 患者。我们的数据还表明,循环代谢物可能在肝切除术后微转移生长和伴随的早期肿瘤复发中发挥重要的病理生理作用。然而,这一提议的代谢组学概念的临床适用性和性能需要在未来的研究中得到独立验证。

更新日期:2021-06-24
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