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DOI: 10.1055/s-0039-1692110
Clinical relevance of circulating MACC1 and S100A4 transcripts in serum of ovarian cancer patients
Publication History
Publication Date:
24 May 2019 (online)
Background:
Metastasis-associated in colon cancer 1 (MACC1) and S100 calcium binding protein A4 (S100A4) promote metastasis. Their overexpression in the tumor was proposed as a prognostic and/or predictive biomarker for a variety of solid malignancies, including ovarian cancer. However, clinical relevance of circulating MACC1 and S100A4 transcripts as blood-based biomarkers for ovarian cancer is unknown. Therefore, the objective of our study was to systematically track serum levels of both transcripts in the course of surgery and adjuvant therapy and to analyze their clinical relevance for ovarian cancer.
Methods:
The levels of MACC1 and S100A4 transcripts were analyzed in a total of 318 serum samples from 79 ovarian cancer patients (thereof 80% FIGO III or IV), including samples at primary diagnosis and at 4 follow-up time points in the course of treatment. MACC1 was relatively quantified by RT-qPCR and S100A4 was absolutely quantified by digital droplet PCR.
Results:
MACC1 and S100A4 transcripts were significantly elevated in serum of ovarian cancer patients, compared to healthy controls (p = 0.024; p < 0.001) and showed a highly concordant (CA125 independent) dynamic in the course of treatment. Higher levels of MACC1 and S100A4 at primary diagnosis paralleled advanced disease (p = 0.023; p = 0.004) and predicted ineffective primary debulking surgery with no achievement of a macroscopically complete tumor resection (p = 0.011; p = 0.006). Moreover, higher levels of MACC1 and S100A4 at primary diagnosis indicated poor DFS (p = 0.0035; p = 0.0019) and OS (p < 0.001; p = 0.001).
Conclusion:
This is the first liquid biopsy approach, systematically analyzing MACC1 and S100A4 transcripts in ovarian cancer and proposing their prognostic capacity at primary diagnosis.