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.
Highlights
Despite a decreasing incidence in Western countries, colorectal cancer (CRC) has remained one of the most common types of cancer worldwide, representing a major cause of cancer-related death [1]
Existing preoperative stratification algorithms such as the Fong score, which are mainly based on imaging techniques, the patients’ liver function and the clinical performance status, are often inconclusive and frequently do not sufficiently identify the subgroup of colorectal liver metastases (CRLM) patients that benefit from surgical resection in terms of overall survival [10]
CRLM showed a strong immunohistochemical staining for osteopontin compared to the healthy liver tissue (Figure 1c, left column)
Summary
Despite a decreasing incidence in Western countries, colorectal cancer (CRC) has remained one of the most common types of cancer worldwide, representing a major cause of cancer-related death [1]. About 50% of CRC patients develop colorectal liver metastasis (CRLM) during the course of disease [3,4]. Hepatic resection has evolved as the standard curative intent therapy for CRLM patients in daily practice. Disease recurrence rates even after successful CRLM resection are high and about 65% of resected patients develop hepatic relapse within three years after surgery [4,8,9]. Existing preoperative stratification algorithms such as the Fong score, which are mainly based on imaging techniques, the patients’ liver function and the clinical performance status, are often inconclusive and frequently do not sufficiently identify the subgroup of CRLM patients that benefit from surgical resection in terms of overall survival [10]
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