Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image

Abstract

Purpose: Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker.

Methods: We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies.

Results: A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed.

Conclusions: The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.

Keywords: Dynamic detection; Fibroblast activation protein; Glioma; Image; Serum.

Fig. 1

The relative level of preoperative serum FAP autoantibodies in a cohort of 87 patients with different WHO-grade gliomas was assessed using the enzyme-linked immunosorbent assay (ELISA) (I). The scatterplot depicts the autoantibody relative serum FAP level in postoperative 87 patients with grade 2–4 glioma (II). The correlation between serum autoantibody relative FAP level and molecular pathology in gliomas has been established. The levels of serum autoantibodies relative to FAP in IDH-mutant gliomas are found to be significantly elevated compared to IDH-wild type gliomas of the same grades 2 and 3. FAP expression is more common in IDH-wildtype GBMs than in IDH-mutant gliomas with WHO 4 grade (III a, b, c). Serum autoantibody relative FAP levels are higher in 1p/19q codeleted gliomas than in 1p/19q non-codeleted gliomas of identical grades 2 and 3. The likelihood of FAP level is higher in 1p/19q non-codeleted glioblastomas (GBMs) compared to 1p/19q codeleted gliomas with WHO 4 grade (III d, e, f). Serum autoantibody relative FAP levels The levels of serum autoantibodies relative FAP are typically elevated in MGMT-methylated gliomas compared to MGMT-unmethylated gliomas. There is no apparent distinction observed between GBMs with MGMT methylation and those without methylation (III g, h, i)

Fig. 2

All the images exhibit axial orientation, displaying T1 and T2-weighted intensity, as well as T1-weighted intensity following contrasted enhancement. The presented case exhibits the presence of a mass in the medial temporal lobe on the right side, characterized by an indeterminate border and lack of enhancement (I a).The presented case exhibits the presence of left temporal lobe glioblastoma, characterized by heterogeneous enhancement and occupying effects (I b). The present case involves an anaplastic astrocytoma (WHO grade 3) located in the right temporal insular lobe. Notably, there is evident peripheral edema surrounding the tumor, along with a central dot-shaped enhancement (I c). The case unveiled the presence of a mass in the left frontal lobe, accompanied by edema and sporadic enhancement (I d). Immunohistochemistry affirms the wide expression of FAP in glioma tissue. Typical immunohistochemistry image of FAP expression was represented in the four glioma patients’ section. Tumor tissue sections were stained to determine FAP expression (brown). In many areas, spindle cells are strongly stained for FAP, which was also observed in cells surrounding blood vessels (II a-d). FAP-positive cells proliferate primarily around microvascular protrusions in GBM (II b). Scale bars 100 μm in a for a–d (II)

Fig. 3

Longitudinal bead-assisted ELISA data from 33 glioma patients show dynamic variation in serum autoantibody relative FAP levels, as well as tumor status. The levels of serum autoantibody relative FAP exhibite a significant increase during the progression of the tumor, followed by a substantial decrease upon disease remission. There was no significant variation observed in FAP levels among patients with stable tumors (I). During adjuvant chemotherapy, a positive correlation was observed between serum autoantibody relative FAP levels and tumor volume (II)