Expression and clinical significance of minichromosome maintenance protein 8 in glioma
ZHOU Chengying1 ZHAO Benhuo2 BAO Lei1 HUA Fang1 YANG Xinxin1
1.Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, Xuzhou 221000, China; 2.Department of Digestive, the Affiliated Hospital of Yangzhou University, Jiangsu Province, Yangzhou 225102, China
Abstract：Objective To analyze the clinical significance and expression of minichromosome maintenance protein 8 (MCM8) in glioma tissues. Methods MRNA data and the differential expression of MCM8 was extracted and analyzed from 17 glioma and four para-cancerous tissues involved in GSE19728, 156 glioma and five para-cancerous tissues involved in TCGA. China Glioma Genome Atlas analyzed the expressions of MCM8 in various pathological types of gliomas and para-cancerous tissues and the effects of MCM8 on the prognosis of glioma. Enrichment analysis of MCM8 co-expression genes in glioma was performed by DAVID. Interaction molecules of MCM8 were analyzed by STRING and PINA. Correlations between MCM8 expression and the immune infiltrations in the microenvironment of glioma were explored by TISIDB database. Results MCM8 expression in glioma was higher than para-cancerous tissues, the difference was statistically significant (P＜0.05). Expressions of MCM8 in gliomas of World Health Organization（WHO） grade Ⅲ and Ⅳ were higher than grade Ⅱ, the differences were highly statistically significant (P＜0.01). The survival rates of glioma patients with high MCM8 expression was lower than those with low expression, the differences were statistically significant (P＜0.05). MCM8 was involved in the regulation of intracellular DNA replication, response to damage stimulus and other processes. MCM8 was closely related to the members of the cell division control protein and DNA polymerase families. MCM8 expression level in glioma was negatively related to the infiltrating levels of activated T cell, B cell, natural killer cell, dendritic cell and macrophagocytes in the tumor microenvironment (r＜0, P＜0.05). Conclusion MCM8 is overexpressed in glioma and closely correlated with the progression and prognosis of glioma.
[1] Alexopoulos G，Zhang J，Karampelas I，et al. Long-Term Time Series Forecasting and Updates on Survival Analysis of Glioblastoma Multiforme：A 1975-2018 Population-Based Study [J]. Neuroepidemiology，2022，56（2）：75-89. [2] Sung H，Ferlay J，Siegel RL，et al. Global Cancer Statistics 2020： GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [J]. CA Cancer J Clin，2021，71（3）：209-249. [3] Nicholson JG，Fine HA. Diffuse Glioma Heterogeneity and Its Therapeutic Implications [J]. Cancer Discov，2021，11（3）：575-590. [4] Ren Z，Li J，Zhao S，et al. Knockdown of MCM8 functions as a strategy to inhibit the development and progression of oste- osarcoma through regulating CTGF [J]. Cell Death Dis，2021， 12（4）：376. [5] Wang X，Zhang L，Song Y，et al. MCM8 is regulated by EGFR signaling and promotes the growth of glioma stem cells through its interaction with DNA-replication-initiating factors [J]. Oncogene，2021，40（27）：4615-4624. [6] Reardon DA，Brandes AA，Omuro A，et al. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma：The CheckMate 143 Phase 3 Randomized Clinical Trial [J]. JAMA Oncol，2020，6（7）：1003-1010. [7] Ghiaseddin AP，Shin D，Melnick K，et al. Tumor Treating Fields in the Management of Patients with Malignant Glio- mas [J]. Curr Treat Options Oncol，2020，21（9）：76. [8] 周江芬，赖名耀，蔡林波.老年高级别胶质瘤临床特点及预后分析[J].中国医药导报，2022，19（23）：27-31. [9] Weller M，van den Bent M，Preusser M，et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adul- thood [J]. Nat Rev Clin Oncol，2021，18（3）：170-186. [10] Franceschi E，Tosoni A，Bartolini S，et al. Histopathological grading affects survival in patients with IDH-mutant grade Ⅱ and grade Ⅲ diffuse gliomas [J]. Eur J Cancer，2020，137： 10-17. [11] Sheng J，He X，Yu W，et al. p53-targeted lncRNA ST7-AS1 acts as a tumour suppressor by interacting with PTBP1 to suppress the Wnt/beta-catenin signalling pathway in gli- oma [J]. Cancer Lett，2021，503：54-68. [12] Hoeijmakers JH. Genome maintenance mechanisms for pre- venting cancer [J]. Nature，2001，411（6835）：366-374. [13] Hoeijmakers JH. Genome maintenance mechanisms are criti- cal for preventing cancer as well as other aging-associated diseases [J]. Mech Ageing Dev，2007，128（7/8）：460-462. [14] Roos WP，Kaina B. DNA damage-induced cell death by ap- optosis [J]. Trends Mol Med，2006，12（9）：440-450. [15] Wong RS. Apoptosis in cancer：from pathogenesis to treat- ment [J]. J Exp Clin Cancer Res，2011，30：87. [16] Lisova AE，Baranovskiy AG，Morstadt LM，et al. Human DNA polymerase alpha has a strong mutagenic potential at the initial steps of DNA synthesis [J]. Nucleic Acids Res，2022， 50（21）：12266-12273. [17] Lin YC，Liu D，Chakraborty A，et al. Orc6 is a component of the replication fork and enables efficient mismatch repair [J]. Proc Natl Acad Sci U S A，2022，119（22）：e2121406119. [18] 赵锛活，吴云江，吴健，等.微小染色体维持蛋白8在食管癌组织的表达及临床意义[J].中华实验外科杂志，2022， 39（8）：1488-1490. [19] Zheng Y，Chen Z，Han Y，et al. Immune suppressive land- scape in the human esophageal squamous cell carcinoma microenvironment [J]. Nat Commun，2020，11（1）：6268. [20] Huang XM，Liu XS，Lin XK，et al. Role of plasmacytoid dendritic cells and inducible costimulator-positive regu- latory T cells in the immunosuppression microenvironment of gastric cancer [J]. Cancer Sci，2014，105（2）：150-158. [21] Zhang D，He W，Wu C，et al. Scoring System for Tumor- Infiltrating Lymphocytes and Its Prognostic Value for Gas- tric Cancer [J]. Front Immunol，2019，10：71. [22] Mantovani A，Allavena P，Sica A，et al. Cancer-related inflammation [J]. Nature，2008，454（7203）：436-444. [23] Chen Z，Feng X，Herting CJ，et al. Cellular and Molecular Identity of Tumor-Associated Macrophages in Gliobla- stoma [J]. Cancer Res，2017，77（9）：2266-2278. [24] Klemm F，Maas RR，Bowman RL，et al. Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells [J]. Cell，2020，181（7）：1643-1660，e1617. [25] Friebel E，Kapolou K，Unger S，et al. Single-Cell Mapping of Human Brain Cancer Reveals Tumor-Specific Instr- uction of Tissue-Invading Leukocytes [J]. Cell，2020，181（7）： 1626-1642，e1620.
2023, Vol. 20 
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