The Evaluation of AREG, MMP-2, CHI3L1, GFAP, and OPN Serum Combined Value in Astrocytic Glioma Patients’ Diagnosis and Prognosis

Abstract

Gliomas account for approximately 70% of primary brain tumors in adults. Of all gliomas, grade IV astrocytoma, also called glioblastoma, has the poorest overall survival, with <5% of patients surviving five years after diagnosis. Due to the aggressiveness, lethal nature, and impaired surgical accessibility of the tumor, early diagnosis of the tumor and, in addition, prediction of the patient’s survival time are important. We hypothesize that combining the protein level values of highly recognizable glioblastoma serum biomarkers could help to achieve higher specificity and sensitivity in predicting glioma patient outcome as compared to single markers. The aim of this study was to select the most promising astrocytoma patient overall survival prediction variables from five secretory proteins—glial fibrillary acidic protein (GFAP), matrix metalloproteinase-2 (MMP-2), chitinase 3-like 1 (CHI3L1), osteopontin (OPN), and amphiregulin (AREG)—combining them with routinely used tumor markers to create a Patient Survival Score calculation tool. The study group consisted of 70 astrocytoma patients and 31 healthy controls. We demonstrated that integrating serum CHI3L1 and OPN protein level values and tumor isocitrate dehydrogenase 1 IDH1 mutational status into one parameter could predict low-grade astrocytoma patients’ two-year survival with 93.8% accuracy.

Astrocytic Chitinase‐3‐like protein 1 in neurological diseases: Potential roles and future perspectives

“…These results were obtained from the website, http://tisch.comp-genom ics.org. High protein expression of CHI3L1 has also been identified in CSF and is considered a diagnostic biomarker in patients with brain malignancies(Schmid et al, 2021).5.7.2 | Role of CHI3L1 in gliomaCHI3L1 plays a role in inflammation, tumor cell proliferation and differentiation, protection from apoptosis, the stimulation of angiogenesis(Shao et al, 2015), and the regulation of extracellular tissue remodeling(Urbanaviciute et al, 2020). CHI3L1 in glioma regulates invasion, growth, metastasis, and patient survivalKu et al, 2011;Qin et al, 2017;Zhao et al, 2020), and it drives GBM immunosuppression.…”

A grasp on GFAP in Glioma

“…Both Shih et al and Urbanaviciute et al compared sGFAP levels in grade I/II patients and grade III/IV patients combined. Both studies did not find a significant difference in sGFAP levels between the high-and low grade groups (Shih et al 2017;Urbanavičiūtė, Skauminas, and Skiriutė 2020) or between glioma patients and controls (Urbanavičiūtė, Skauminas, and Skiriutė 2020). In the study by Shih and colleagues the (Reitsma et al 2005).…”

“…Further investigation into sGFAP positive-and negative subgroups of GBM patients is needed to determine the diagnostic value of sGFAP. So far, only three studies determined sGFAP in subgroups of patients classified according to WHO 2016 (Urbanavičiūtė, Skauminas, and Skiriutė 2020;Vietheer et al 2017;, and two of these studies showed that higher sGFAP levels are mainly associated with IDHwt tumours Vietheer et al 2017). Integration of additional genetic markers into sGFAP analysis may link the presence of sGFAP to specific molecular subgroups of GBM patients.…”

“…Both Kiviniemi et al and Vietheer et al measured higher sGFAP levels in glioma grade IV patients with IDH-1 wildtype (IDHwt) status, compared to glioma grade IV with a IDH-1 mutation (IDHmut) Vietheer et al 2017). Urbanaviciute et al however did not detect differences between the IDHwt and IDHmut groups (Urbanavičiūtė, Skauminas, and Skiriutė 2020). At last, Tichy and colleagues found higher rates of MGMT promotor methylation in patients with high sGFAP levels, but this correlation was not found by Kiviniemi et al Tichy et al 2015).…”

“…Some studies report no association between sGFAP levels and OS or PFS (Shih et al 2017;Vietheer et al 2017). However, detection or an increase of sGFAP has also been linked to a less favourable outcome Lyubimova et al 2020a), as well as a (trend towards) more (Urbanavičiūtė, Skauminas, and Skiriutė 2020;Ilhan-Mutlu et al 2013) favourable outcome of grade IV glioma patients. Of the studies that investigated treatment response, Baumgarten et al, Kiviniemi et al and Husain et al showed a significant increase of sGFAP in grade IV patients in the week after surgery (Husain et al 2012;Baumgarten et al 2018;.…”