Slattery Kaitlynn, Kauss McKenzie C, Raval Dhaivat, Hsieh Emory, Choi Ann, Davis Tara S, Robins Kimberly R, Miller Hope, Vera Elizabeth, Wright Michelle L, Penas-Prado Marta, Gilbert Mark R, Mendoza Tito, Armstrong Terri S, Guedes Vivian A
National Cancer Institute Neuro-Oncology Branch, National Institutes of Health (NIH), Bethesda, Maryland, USA.
National Cancer Institute (NCI) Office of Patient-Centered Outcomes Research, National Institutes of Health (NIH), Bethesda, Maryland, USA.
Neurooncol Adv. 2025 Jan 16;7(1):vdaf002. doi: 10.1093/noajnl/vdaf002. eCollection 2025 Jan-Dec.
Cognitive dysfunction is common among patients with malignant glioma, yet the underlying mechanisms of this dysfunction remain unclear. Protein markers of neurodegeneration, inflammation, and vascular damage have been associated with central nervous system pathology and with cognitive changes in neurological diseases, but their clinical utility in gliomas is unknown. This study examined the relationships between cognitive dysfunction, tumor isocitrate dehydrogenase (IDH) mutation status in gliomas, and a panel of blood-based protein biomarkers.
This retrospective cohort study included 73 glioma patients with either IDH-mutant ( = 45) or IDH-wildtype tumors ( = 28) enrolled in a natural history study. Cognitive function was assessed using the Montreal Cognitive Assessment (scores <26 indicated cognitive dysfunction). Serum levels of 17 proteins were measured using ultrasensitive assays.
Cognitive dysfunction was present in 53% of participants ( = 39), and more frequently in the IDH-wildtype group (75%) than in the IDH-mutant group (40%). Patients with wildtype tumors had higher levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin-6 (IL-6), and tumor necrosis factor-α than patients with IDH-mutant tumors, which remained in multivariate analysis. ICAM-1 and IL-10 were higher in patients with cognitive dysfunction compared to those with normal cognition, even after adjusting for tumor IDH-mutation status, age, tumor grade, and surgery history.
Cognitive dysfunction was associated with protein markers linked to vascular damage and inflammation regardless of tumor IDH status. Our findings suggest an association of cognitive dysfunction with heightened systemic inflammatory status that requires further interrogation for its role in pathophysiologic mechanisms.
认知功能障碍在恶性胶质瘤患者中很常见，但其潜在机制仍不清楚。神经退行性变、炎症和血管损伤的蛋白质标志物与中枢神经系统病理以及神经疾病中的认知变化有关，但其在胶质瘤中的临床应用尚不清楚。本研究探讨了认知功能障碍、胶质瘤中肿瘤异柠檬酸脱氢酶（IDH）突变状态与一组血液蛋白生物标志物之间的关系。
这项回顾性队列研究纳入了73例参加自然史研究的胶质瘤患者，其中45例为IDH突变型肿瘤，28例为IDH野生型肿瘤。使用蒙特利尔认知评估量表评估认知功能（得分<26表明存在认知功能障碍）。采用超敏检测法测量17种蛋白质的血清水平。
53%的参与者（n = 39）存在认知功能障碍，IDH野生型组（75%）比IDH突变型组（40%）更常见。野生型肿瘤患者的细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1、白细胞介素-6（IL-6）和肿瘤坏死因子-α水平高于IDH突变型肿瘤患者，并在多变量分析中保持显著差异。即使在调整肿瘤IDH突变状态、年龄、肿瘤分级和手术史后，认知功能障碍患者的ICAM-1和IL-10水平仍高于认知正常患者。
无论肿瘤IDH状态如何，认知功能障碍都与血管损伤和炎症相关的蛋白质标志物有关。我们的研究结果表明认知功能障碍与全身炎症状态增强有关，这需要进一步探究其在病理生理机制中的作用。
