2022 年第 10 期 第 17 卷

人脑胶质瘤组织中多磷酸肌醇-5-磷酸酶B的表达及临床意义

Expression and clinical significance of inositol polyphosphate-5-phosphatase B in human glioma

作者：姚开场胡致远杨力权高尚锋于如同

英文作者：Yao Kaichang Hu Zhiyuan Yang Liquan Gao Shangfeng Yu Rutong

单位：徐州医科大学附属医院神经外科徐州医科大学神经系统疾病研究所，徐州221002

英文单位：Department of Neurosurgery the Affiliated Hospital of Xuzhou Medical University Institute of Nervous System Diseases Xuzhou Medical University Xuzhou 221002 China

关键词：脑胶质瘤；多磷酸肌醇-5-磷酸酶B；世界卫生组织分级；生存分析

英文关键词：Glioma;Inositolpolyphosphate-5-phosphataseB；WorldHealthOrganizationstages;Survivalanalysis

• 摘要：

• 目的 探讨多磷酸肌醇-5-磷酸酶B（INPP5B）在人脑胶质瘤组织中的表达情况及临床意义。方法 收集2016年2月至2021年8月徐州医科大学附属医院手术切除的脑胶质瘤组织标本，另选取同一时期颅脑外伤患者切除的新鲜脑组织作为非瘤脑组织标本，共收集冷冻标本24例（非瘤脑组织6例、脑胶质瘤组织18例）、石蜡标本50例（非瘤脑组织10例、脑胶质瘤组织40例）。收集并分析美国肿瘤基因组图谱数据（TCGA）、中国脑胶质瘤基因组图谱计划（CGGA）和GSE16011数据库胶质瘤数据集中正常脑组织和不同世界卫生组织（WHO）分级胶质瘤组织INPP5B mRNA表达情况以及不同异柠檬酸脱氢酶（IDH）分型胶质瘤组织INPP5B mRNA表达情况。采用蛋白质印迹法检测本院冷冻标本INPP5B蛋白表达量，免疫组织化学法检测石蜡标本INPP5B阳性细胞率。分析CGGA中脑胶质瘤患者及本院石蜡标本脑胶质瘤患者的生存情况。结果 TCGA和CGGA中，WHO Ⅱ级、Ⅲ级、Ⅳ级脑胶质瘤组织INPP5B mRNA表达量呈递增趋势（均P＜0.01）；GSE16011数据库中，WHO Ⅲ级、Ⅳ级脑胶质瘤组织INPP5B mRNA表达量均高于WHO Ⅱ级（均P＜0.05）。TCGA及CGGA中，IDH突变型胶质瘤组织INPP5B mRNA表达量均低于IDH野生型（均P＜0.001）。本院收集的冷冻标本中，WHO Ⅱ级、Ⅲ级、Ⅳ级脑胶质瘤INPP5B蛋白表达量逐渐上升，但非瘤脑组织及各WHO分级脑胶质瘤组织组间比较差异无统计学意义（P=0.494）。本院收集的石蜡标本中，WHO Ⅱ级、Ⅲ级、Ⅳ级脑胶质瘤组织INPP5B阳性细胞率呈递增趋势［（24±13）%、（39±20）%、（53±23）%］，且均高于非瘤脑组织［（23±10）%］（均P＜0.01）；IDH突变型脑胶质瘤组织INPP5B阳性细胞率低于IDH野生型，但差异无统计学意义（P=0.321）。CGGA中，INPP5B mRNA高表达WHO Ⅱ级、Ⅲ级脑胶质瘤患者累积生存率低于低表达患者（P＜0.001、P=0.001）；本院收集的石蜡标本中，INPP5B高表达WHO Ⅱ~Ⅳ级患者累积生存率低于低表达患者，但差异无统计学意义（P=0.155）。结论 INPP5B的表达随脑胶质瘤WHO分级增加而增加，但INPP5B与脑胶质瘤患者预后的关系仍需进一步研究。

• Objective  To investigate the expression and clinical significance of inositol polyphosphate-5-phosphatase B (INPP5B) in human glioma. Methods Surgically resected glioma samples in the Affiliated Hospital of Xuzhou Medical University from February 2016 to August 2021 were collected. Fresh brain tissues resected from patients with craniocerebral trauma were selected as non-tumor brain samples. Finally, 24 cases of frozen samples (6 cases of non-tumor brain tissue and 18 cases of glioma) and 50 cases of paraffin samples (10 cases of non-tumor brain tissue and 40 cases of glioma) were collected. The expression of INPP5B mRNA in normal brain tissues, different World Health Organization (WHO) stage of glioma, and different isocitrate dehydrogenase (IDH) stage of glioma were collected and analyzed from the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and glioma data set of GSE16011 database. Western blotting was used to detect the expression of INPP5B protein in frozen samples from the hospital, and immunohistochemistry was used to detecet INPP5B positive cell rate in paraffin samples. The survival status of glioma patients from CGGA and glioma patients with paraffin samples from the hospital were analyzed. Results In TCGA and CGGA, expressions of INPP5B mRNA in glioma of WHO Ⅱ, Ⅲ and Ⅳ showed an increasing trend (all P<0.01); in GSE16011 database, expressions of INPP5B mRNA in glioma of WHO Ⅲ and Ⅳ were higher than those in WHO Ⅱ (both P<0.05). In TCGA and CGGA, expressions of INPP5B mRNA in IDH mutant type of glioma were lower than those in IDH wild type (both P<0.001). In frozen samples in the hospital, the expression of INPP5B protein was on the rise in glioma of WHO Ⅱ, Ⅲ and Ⅳ, while there was no significant difference among non-tumor brain tissues and different WHO stages of glioma (P=0.494). In paraffin samples in the hospital, INPP5B positive cells rate in glioma of WHO Ⅱ, Ⅲ and Ⅳ showed an increasing trend ［（24±13）%,（39±20）%,（53±23）%］, and the rates were higher than those in non-tumor brain tissues ［（23±10）%］(all P<0.01); INPP5B positive cell rate in IDH mutant type of glioma was lower than that in IDH wild type, while the difference was not statistically significant (P=0.321). In CGGA, the cumulative survival in patients with high INPP5B expression who had glioma of WHO Ⅱ and Ⅲ was lower than that in patients with low INPP5B expression (P<0.001, P=0.001). In paraffin samples in the hospital, the cumulative survival in patients with high INPP5B expression who had glioma of WHO Ⅱ-Ⅳ was lower than that in patients with low INPP5B expression, while the difference was not statistically significant (P=0.155). Conclusion The expression of INPP5B increases with the rise of WHO stage of glioma. However, the association between INPP5B and the prognosis of glioma patients still needs further investigation.