Dan G Duda1, Simona O Dima2,3, Dana Cucu4, Andrei Sorop3, Sebastian Klein5, Marek Ancukiewicz6, Shuji Kitahara1,7, Speranta Iacob2,3, Nicolae Bacalbasa2,3, Dana Tomescu3,8, Vlad Herlea3,9, Cristiana Tanase10, Adina Croitoru3,11, Irinel Popescu2,3. 1. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom St., Cox-734, Boston, MA 02114, USA. 2. Center of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania. 3. Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania. 4. Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 030018 Bucharest, Romania. 5. Institute for Pathology, University Hospital Cologne, 50937 Cologne, Germany. 6. Probabilitas LLC, Acton, MA 01720, USA. 7. Department of Anatomy, Tokyo Women Medical University, Tokyo 162-8666, Japan. 8. Department of Anesthesia and Intensive Care, Fundeni Clinical Institute, 022328 Bucharest, Romania. 9. Department of Pathology, Fundeni Clinical Institute, 022328Bucharest, Romania. 10. Department of Biochemistry-Proteomics, Victor Babes National Institute of Pathology, 050088 Bucharest, Romania. 11. Department of Medical Oncology, Fundeni Clinical Institute, 022328 Bucharest, Romania.
Abstract
Background: Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Angiogenesis and inflammation are hallmarks of HCC progression and therapeutic targets. Methods: We retrospectively evaluated preoperative clinical variables and circulating (plasma) biomarkers of angiogenesis and inflammation in a cohort of HCC patients who underwent liver resection (LR) or transplantation (LT). Biomarker correlation with outcomes-freedom of liver recurrence (FLR), disease-free survival (DFS) and overall survival (OS)-was tested using univariate and multivariate Cox regression analyses. Results: Survival outcomes associated with sVEGFR1, VEGF and VEGF-C in LT patients and with IL-10 in LR patients. Moreover, in LT patients within Milan criteria, higher plasma VEGF and sVEGFR1 were associated with worse outcomes, while in those outside Milan criteria lower plasma VEGF-C associated with better outcomes. Multivariate analysis indicated that adding plasma VEGF or VEGF-C to a predictive model including Milan criteria and AFP improved prediction of DFS and OS (all p < 0.05). Conclusion: Survival outcomes after LR or LT differentially associated with angiogenic and inflammatory biomarkers. High plasma VEGF correlated with poorer prognosis within Milan criteria while low plasma VEGF-C associated with better prognosis outside Milan criteria. These candidate biomarkers should be further validated to improve patient stratification.
Background: Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Angiogenesis and inflammation are hallmarks of HCC progression and therapeutic targets. Methods: We retrospectively evaluated preoperative clinical variables and circulating (plasma) biomarkers of angiogenesis and inflammation in a cohort of HCCpatients who underwent liver resection (LR) or transplantation (LT). Biomarker correlation with outcomes-freedom of liver recurrence (FLR), disease-free survival (DFS) and overall survival (OS)-was tested using univariate and multivariate Cox regression analyses. Results: Survival outcomes associated with sVEGFR1, VEGF and VEGF-C in LT patients and with IL-10 in LR patients. Moreover, in LT patients within Milan criteria, higher plasma VEGF and sVEGFR1 were associated with worse outcomes, while in those outside Milan criteria lower plasma VEGF-C associated with better outcomes. Multivariate analysis indicated that adding plasma VEGF or VEGF-C to a predictive model including Milan criteria and AFP improved prediction of DFS and OS (all p < 0.05). Conclusion: Survival outcomes after LR or LT differentially associated with angiogenic and inflammatory biomarkers. High plasma VEGF correlated with poorer prognosis within Milan criteria while low plasma VEGF-C associated with better prognosis outside Milan criteria. These candidate biomarkers should be further validated to improve patient stratification.
Authors: Kohei Shigeta; Aya Matsui; Hiroto Kikuchi; Sebastian Klein; Emilie Mamessier; Ivy X Chen; Shuichi Aoki; Shuji Kitahara; Koetsu Inoue; Ayako Shigeta; Tai Hato; Rakesh R Ramjiawan; Daniel Staiculescu; Dieter Zopf; Lukas Fiebig; Gabriela S Hobbs; Alexander Quaas; Simona Dima; Irinel Popescu; Peigen Huang; Lance L Munn; Mark Cobbold; Lipika Goyal; Andrew X Zhu; Rakesh K Jain; Dan G Duda Journal: J Immunother Cancer Date: 2020-11 Impact factor: 13.751