Abstract
Simple SummaryAdvances in circulating tumor cells (CTCs) research could improve the way we diagnose, treat and monitor epithelial ovarian cancer (EOC) patients. In this study, we investigated the interplay between inflammation-induced systemic catabolic markers and the presence of CTCs and patient outcome, and showed that the presence of CTCs goes hand-in-hand with an increased protein turnover and immune activation. We integrated the information provided by measuring the plasma levels of albumin, tryptophan and its metabolite kynurenine in a combined score for cancer exhaustion (CCES). Our study indicates that not only could the CCES be a useful prognostic biomarker in women with EOC, but also that the interaction between the systemic microenvironment and CTCs is worth investigating in further studies.We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, c-reactive protein (CRP) and the kynurenine to tryptophan ratio (Kyn/Trp) as well as the CTC-related marker cyclophilin C (PPIC) were obtained before primary therapy and were correlated to the respective clinical and outcome data. The information provided by albumin and Kyn/Trp was integrated in a combined score for cancer exhaustion (CCES). A high CCES characterized by hypoalbuminemia and a high Kyn/Trp was associated with both decreased overall and progression-free survival, independent from other known prognostic factors in a multivariable analysis. The presence of PPIC-positive CTCs was significantly associated with a high CCES, highlighting that the interplay between the systemic microenvironment and CTCs should be considered in “liquid biopsy” biomarker assessment.
Highlights
Ovarian cancer is the 7th most common cancer in women worldwide [1]
We further described the kynurenine-to-tryptophan ratio (Kyn/Trp ratio) as a biomarker for immune activation and its association with the presence of circulating tumor cells (CTCs), an aspect that still needs to be further developed in CTC research
In the present study, we determined whether specific systemic characteristics for cancer exhaustion correlate and are associated with the presence of circulating tumor cells and clinical outcome in patients with primary advanced epithelial ovarian cancer (EOC) recruited within the multicentered OVCAD study [17]
Summary
Ovarian cancer is the 7th most common cancer in women (and the 18th most common cancer overall) worldwide [1]. Markers for inflammation as well as scores, e.g., the Glasgow Prognostic Score, have a prognostic relevance in EOC as well as other solid tumors; they are not currently used in everyday clinical practice and in the management of EOC patients Proinflammatory cytokines such as IL1, IL6 and TNF and growth factors are released as part of the systemic inflammatory response to a tumor, affecting albumin synthesis as well as CRP secretion [11,12]. In the present study, we determined whether specific systemic characteristics for cancer exhaustion correlate and are associated with the presence of circulating tumor cells and clinical outcome in patients with primary advanced EOC recruited within the multicentered OVCAD study [17]
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