Comparison of endoplasmic reticulum chaperone gene expression and dosimetric findings before and after gamma knife radiosurgery in meningioma

Abstract Gamma Knife radiosurgery (GKRS) is a widely used treatment for intracranial meningiomas; however, its effects on endoplasmic reticulum (ER) stress–related molecular pathways remain unclear. This study aimed to evaluate changes in circulating ER stress–associated chaperone proteins before and three months after GKRS and to explore their relationship with radiological and dosimetric findings. A total of 27 patients with meningioma treated with GKRS and 20 healthy controls were included. Peripheral blood samples were collected prior to treatment and three months post-treatment. Serum levels of glucose-regulated protein 78 (GRP78), calreticulin (CALR), calnexin (CNX), mesencephalic astrocyte-derived neurotrophic factor (MANF), protein disulfide isomerase (PDI), and protein disulfide isomerase A3 (PDIA3) were measured using enzyme-linked immunosorbent assay (ELISA). Magnetic resonance imaging was used to evaluate tumor volume and peritumoral edema. Dosimetric parameters were obtained from the treatment planning system. Pre-treatment levels of PDIA3, CALR, CNX, MANF, and PDI were higher in patients with meningioma than in healthy controls, with statistically significant differences observed for PDIA3, CALR, CNX, MANF, and PDI. Following GKRS, all six investigated proteins showed numerical decreases. Nominally significant pre- to post-treatment reductions were observed for PDIA3, CALR, MANF, and PDI; however, after Holm correction for multiple comparisons, only the reduction in CALR remained statistically significant. MRI assessment demonstrated tumor volume reduction in 5 of 27 patients (18.5%), while tumor volume remained stable in 22 patients (81.5%). GKRS was associated with measurable changes in circulating ER stress–related proteins. These findings indicate a temporal association rather than a causal effect and should be interpreted with caution. Although these markers are not suitable as standalone biomarkers, they may provide complementary information when evaluated together with radiological findings. Further longitudinal and mechanistic studies are needed to determine their biological significance and potential clinical relevance.