Values of Ki-67 expression level and 4 molecular types for risk classification of prognosis in medulloblastoma / 肿瘤研究与临床

ABSTRACT

Objective:To investigate the values of Ki-67 expression level and 4 molecular types for risk classification of prognosis in patients with medulloblastoma (MB).Methods:A retrospective study of 92 MB patients who underwent surgery and were confirmed by postoperative pathology in the First Affiliated Hospital of Zhengzhou University from January 2009 to January 2018 was performed. The clinical data and survival data of the patients were collected and sorted out. The overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method, and the log-rank test was performed. Risk stratification of prognosis of patients was performed according to the Ki-67 expression level combined with molecular typing, the low-risk group had Ki-67 positive index ≤50% and WNT or SHH subtype, the medium-risk group had Ki-67 positive index ≤50% and GROUP 3 or GROUP 4 subtype, or Ki-67 positive index >50% and WNT or SHH subtype), and the high-risk group had Ki-67 positive index >50% and GROUP 3 or GROUP 4 subtype. The differences in OS and PFS among different risk groups were compared. A multivariate Cox proportional hazards model was used to assess factors affecting the survival of patients.Results:There were 50 cases (54.3%) with Ki-67 positive index ≤50% and 42 cases (45.7%) with Ki-67 positive index >50%. The 5-year PFS rate and OS rate of patients with Ki-67 positive index ≤50% were 46.9% and 63.1%, and patients with Ki-67 positive index >50% were 28.5% and 32.0%, there were statistical differences in PFS and OS between the two groups ( P values were 0.020 and 0.028). There were 16 cases (17.4%) of WNT subtype, 14 cases (15.2%) of SHH subtype, 40 cases (43.5%) of GROUP 3 subtype and 22 cases (23.9%) of GROUP 4 subtype, their 5-year PFS rates were 78.0%, 76.0%, 19.2% and 19.9%, respectively, and their 5-year OS rates were 82.1%, 76.0%, 40.2% and 0, respectively. MB patients with GROUP 3 or GROUP 4 subtype had poorer PFS and OS than patients with WNT or SHH subtype ( P values were 0.003 and 0.039). Ki-67 expression level and molecular typing were combined to carry out risk classification of prognosis. There were 12 cases (13.0%) in the low-risk group, 56 cases (60.9%) in the medium-risk group, and 24 cases (26.1%) in the high-risk group . There were statistical differences in PFS and OS among MB patients in low-, medium- and high-risk groups (both P < 0.001). Multivariate Cox regression analysis showed that radiotherapy and risk classification of prognosis as medium risk and low risk were independent protective factors for PFS (radiotherapy vs. no radiotherapy OR = 0.263, 95% CI 0.124-0.556, P < 0.001; medium-risk group vs. high-risk group OR = 0.069, 95% CI 0.008-0.581, P = 0.014; low-risk group vs. high-risk group OR = 0.260, 95% CI 0.131-0.514, P < 0.001); radiotherapy and risk classification of prognosis as low risk were independent protective factors for OS (radiotherapy vs. no radiotherapy OR = 0.221, 95% CI 0.097-0.503, P < 0.001; low-risk group vs. high-risk group OR = 0.328, 95% CI 0.150-0.717, P = 0.005). Conclusions:The expression level of Ki-67 and 4 molecular types are related to the prognosis of MB patients. The combination of the two can be used to classify the prognosis risk of MB patients, which has reference significance for the prediction of prognosis of patients and the selection of individualized treatment plans.