학술논문
Circulating metabolites as a concept beyond tumor biology determining disease recurrence after resection of colorectal liver metastasis.
Document Type
Academic Journal
Author
Jonas JP; Department of Surgery, Hepatico-Pancreato-Biliary Center, Clinicum Favoriten, Vienna, Austria; Department of Visceral and Transplant Surgery, University Hospital of Zurich, Switzerland.; Hackl H; Department of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.; Pereyra D; Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria.; Santol J; Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria.; Ortmayr G; Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria.; Rumpf B; Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria.; Najarnia S; Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria.; Schauer D; Department of Radiology, Clinicum Landstrasse, Vienna, Austria.; Brostjan C; Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria.; Gruenberger T; Department of Surgery, Hepatico-Pancreato-Biliary Center, Clinicum Favoriten, Vienna, Austria.; Starlinger P; Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria; Department of Surgery, Mayo Clinic, Rochester, MN, USA. Electronic address: patrick.starlinger@meduniwien.ac.at.
Source
Publisher: Elsevier Country of Publication: England NLM ID: 100900921 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2574 (Electronic) Linking ISSN: 1365182X NLM ISO Abbreviation: HPB (Oxford) Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)
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.
(Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)