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Circulating Levels of Osteopontin Predict Patients' Outcome after Resection of Colorectal Liver Metastases.

ABSTRACT: For colorectal liver metastases (CRLM), surgical resection is the only potentially curative therapy, but even successfully resected patients often face disease recurrence, leading to 5-year survival rate below 50%. Despite available preoperative stratification strategies, it is not fully elucidated which patients actually benefit from CRLM resection. Here we evaluated osteopontin, a secreted glyco-phosphoprotein, as a biomarker in the context of CRLM resection. Tissue levels of osteopontin were analysed in CRLM using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Pre- and postoperative osteopontin serum concentrations were analysed by enzyme-linked immunosorbent assay (ELISA) in 125 patients undergoing resection of CRLM as well as 65 healthy controls. Correlating with an upregulation of osteopontin tissue expression in CRLM, osteopontin serum levels were significantly elevated in patients with CRLM compared to healthy controls. Importantly, high pre- and post-operative osteopontin serum levels were associated with a poor prognosis after tumour resection. Patients with initial osteopontin serum levels above our ideal cut-off value of 264.4 ng/mL showed a significantly impaired median overall survival of 304 days compared to 1394 days for patients with low osteopontin levels. Together, our data suggest a role of osteopontin as a prognostic biomarker in patients with resectable CRLM that might help to identify patients who particularly benefit from liver resection.

SUBMITTER: Loosen SH

PROVIDER: S-EPMC6262509 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Circulating Levels of Osteopontin Predict Patients' Outcome after Resection of Colorectal Liver Metastases.

Loosen Sven H SH Heise Daniel D Dejong Cees H CH Roy Sanchari S Tacke Frank F Trautwein Christian C Roderburg Christoph C Luedde Tom T Neumann Ulf P UP Binnebösel Marcel M

Journal of clinical medicine 20181026 11

For colorectal liver metastases (CRLM), surgical resection is the only potentially curative therapy, but even successfully resected patients often face disease recurrence, leading to 5-year survival rate below 50%. Despite available preoperative stratification strategies, it is not fully elucidated which patients actually benefit from CRLM resection. Here we evaluated osteopontin, a secreted glyco-phosphoprotein, as a biomarker in the context of CRLM resection. Tissue levels of osteopontin were ...[more]

PMID: 30373147

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Project description:Rationale: Hepatectomy and adjuvant chemotherapy after resection of colorectal liver metastases (CRLM) may improve survival, however, patients which may benefit cannot currently be identified. Postoperative circulating tumor DNA (ctDNA) analysis can detect minimal residual disease (MRD) and predict the prognosis and efficacy of adjuvant chemotherapy. Our study aims to determine the impact of serial ctDNA analysis to predict the outcome among patients undergoing resection of CRLM. Methods: Between May 2018 and October 2019, 91 CRLM patients were prospectively enrolled. Whole exome sequencing was performed in 50 primary and 48 metastatic liver tissues. Targeted sequencing of 451 cancer relevant genes was performed in 50 baseline plasma to determine plasma-tissue concordance. We prospectively investigated changes in the amount and constitution of ctDNA in 271 serial plasma samples taken at different time points (baseline, pre-operation, post-operation, post-operative adjuvant chemotherapy (post-ACT) and recurrence) during the treatment of CRLM. Results: Detected molecular alterations were highly consistent among baseline ctDNA, primary and liver metastases tissue. Patients with a higher variant allele frequency (VAF) level at baseline ctDNA represent a higher tumor burden, and decreased ctDNA during pre-operative chemotherapy predicted better tumor response. Patients with detectable post-operative and post-ACT ctDNA were associated with significantly shorter recurrence-free survival (RFS). ROC analysis showed that post-ACT ctDNA status was superior to post-operative ctDNA status in predicting RFS with an AUROC of 0.79. A significant difference in overall recurrence rate was observed in patients with detectable vs undetectable levels of ctDNA after resection of CRLM (79.4% vs 41.7%) and after completion of adjuvant chemotherapy (77.3% vs 40.7%). During adjuvant chemotherapy, patients with decreased ctDNA VAF after adjuvant chemotherapy had a recurrence rate of 63.6%, compared to 92.3% in patients with increased ctDNA VAF. Conclusions: We envision that dynamic ctDNA analysis, especially in a post-ACT setting, might be used to not only reflect MRD but also to determine rational personalized adjuvant therapy after the resection of CRLM.

Dataset Information

Circulating Levels of Osteopontin Predict Patients' Outcome after Resection of Colorectal Liver Metastases.

Publications

Circulating Levels of Osteopontin Predict Patients' Outcome after Resection of Colorectal Liver Metastases.

Similar Datasets

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