Aberrant Expression of Extracellular Signal-Regulated Kinase and 15-Hydroxyprostaglandin Dehydrogenase Indicates Radiation Resistance and Poor Prognosis for Patients with Clival Chordomas

摘要

ObjectiveTo explore molecular markers of radiosensitivity and prognostic factors in patients with clival chordomas. MethodsRetrospective review was performed of 35 patients. Mean follow-up interval was 66.37 months (range, 29–106 months). Kaplan-Meier method was used for survival analysis. Immunohistochemical staining was used to detect expression levels of extracellular signal-regulated kinase (ERK) and 15-hydroxyprostaglandin dehydrogenase (HPGD). ResultsTotal resection was achieved in 12 cases, subtotal resection was achieved in 12 cases, and partial resection was achieved in 11 cases. Radiation-sensitive group comprised 17 cases, and radiation-resistant (RR) group comprised 18 cases. Five-year progression-free?survival (PFS) rates in total resection and nontotal resection groups were 46.3% and 10.1%, respectively (P?=?0.005). Mean H-scores of ERK in radiation-resistant and radiation-sensitive groups were 110.38 and 82.98, respectively (P?= 0.043). Mean H-scores ofHPGDin radiation-resistant and radiation-sensitive groups were 178.62 and 203.47, respectively (P?= 0.031). Mean PFS in low ERK expression group (58.61 months) was significantly longer than mean PFS in high ERK expression group (24.94 months) (P?= 0.022). Mean PFS in highHPGDexpression group (39.54 months) was significantly longer than mean PFS in low HPGD expression group (9.5 months) (P?= 0.013). ConclusionsRadical resection with protection of important structures is the most effective treatment of clival chordomas. HighHPGDexpression and low ERK expression were associated with radiation sensitivity and better prognosis.HPGDand ERK can be used as biomarkers to predict prognosis and guide treatment.