In the present cohort, a significant decrease in mean serum ApoC1 levels was detected after glioblastoma resection. Consistent with this, significantly more patients had falling serum ApoC1 values after neurosurgery than rising values.
A correlation with confounding medical factors, such as reduction in tumor volume, changes in liver function induced by anesthesia, dilution effects or post-aggression metabolism, was excluded.
However, the lack of correlation of serum ApoC1 values with tumor volume in MRI and with protein expression in histological slides, as well as the missing relationship between ApoC1 levels and survival time do not favor the use of ApoC1 as a serum biomarker or prognostic marker for glioblastoma. .
Our results in patients with glioblastoma reflect the ongoing discussion in current publications regarding malignant disease (Table 3). Two studies in gastric cancer showed that higher serum ApoC1 levels were associated with a better prognosis18.23. In contrast, another recent publication described tumor burden in gastric cancer as elevated in the presence of higher ApoC1 levels.24. Analysis of pancreatic adenocarcinoma indicated that serum ApoC1 levels add to diagnostic accuracy as part of a biomarker panel17. A review of lung cancer patients concluded that the use of serum ApoC1 values does not meet the criteria for a biomarker20.
Similarly, overexpression of ApoC1 mRNA has been analyzed in a multitude of malignancies, including kidney cancer and colorectal cancer, but also gynecological tumors, prostate cancer, and pancreatic or gastric carcinoma. . Conclusions remain equivocal whether elevated mRNA expression is associated with better patient prognosis. Of note, elevated mRNA expression can occur without subsequent elevated protein synthesis, with tumor cell subpopulations that release ApoC1 into the bloodstream subject to additional translational control.
According to the results of the present study, namely a poor correlation of serum ApoC1 levels with tumor volume and intensity of immunohistological staining, the neuroepithelial cell subset is not an important source of circulating ApoC1 protein. Increased detection of ApoC1 immunostaining in the vicinity of necrotic areas supports the theory of its occurrence during microglia activation and macrophage invasion2.3. In this way, ApoC1 expression can be viewed as a physiological response of surrounding tissues and immunocompetent cells to stimulus by glioblastoma cells, similar to stromal responses described in other malignancies, and in line with the increased serum ApoC1 levels detected during recovery. sepsis15.25.
In the cohort presented here, the stimulus and its removal were sufficient to cause detectable and significant changes in the level of serological ApoC1. Comparing these values with results from the literature, one can wonder whether glioblastoma-derived ApoC1 synthesis outweighs the levels obtained by physiological production in the liver or postprandial hyperlipoproteinemia (Table 3). Thus, a single absolute serum value of ApoC1 does not make it possible to conclude on the activity of glioblastoma.
As a next step, to determine whether monitoring subsequent serum levels leads to the detection of a recurrent tumor before it becomes visible on MRI, a much larger multicenter study with long-term follow-up would be needed. Patients should preferentially undergo strict fasting prior to serum collection and samples should be evaluated with a high-throughput technique such as liquid chromatography-mass spectrometry, allowing simultaneous detection of other apolipoproteins.22. In order to exclude hepatic, vascular or obesity-induced interferences, a normalization of the values with respect to body weight or liver volume can be undertaken. These parameters and prerequisites then interfere considerably with the ideal of a simple and easy-to-use biomarker.