|
|
OGT在胰腺癌中表达及预后的相关研究
|
Abstract:
目的：胰腺癌(Pancreatic cancer, PC)是一种高度侵袭性的恶性肿瘤，对患者的生存率造成严重威胁。越来越多的研究表明，糖基化修饰在胰腺癌的发生和发展中扮演着关键角色。O-连接β-N-乙酰氨基葡萄糖转移酶(O-linked N-acetylglucosamine transferase, OGT)是糖基化的关键调节者，其异常表达与多种癌症相关。本研究旨在探究OGT在胰腺癌中的异常表达，并分析其与胰腺癌预后的相关性。方法：回顾性收集2017年1月至2021年1月就诊于青岛大学附属医院确诊胰腺癌且行手术治疗患者的临床及组织病理资料。临床资料包括患者年龄、性别、身体质量指数(Body mass index, BMI)、烟酒史、糖尿病病史、家族史、肿瘤大小、位置、TNM分期、组织浸润及器官转移情况、癌胚抗原(Carcinoembryonic antigen, CEA)、糖类抗原19-9 (Carbohydrate antigen19-9, CA19-9)水平等信息。应用免疫组织化学染色的方法检测癌组织及癌旁胰腺导管组织中OGT的表达水平，并根据表达量的高低分为高表达组和低表达组，分析其与患者临床病理特征及预后的关系。结果：1) 胰腺癌组织中OGT的表达水平与癌旁组织的表达水平之间存在显著统计学差异(P < 0.001)。2) OGT高表达与淋巴结转移、TNM分期有关(P < 0.05)，与年龄、性别、BMI、吸烟、饮酒情况、糖尿病病史、家族史、肿瘤大小、位置、CEA、CA19-9等因素无相关性(P > 0.05)。3) 生存分析表明，OGT的表达水平与患者不良预后存在明显相关性(P = 0.029)。结论：胰腺癌组织中OGT表达水平明显增加，OGT的高表达与淋巴结转移、TNM分期正相关。胰腺癌中OGT的高表达与胰腺癌患者不良预后相关。
Objective: Pancreatic cancer is a highly aggressive tumor that poses a serious threat to the survival rate of patients. A growing body of research suggests that glycosylation regulation plays a key role in the occurrence and progression of pancreatic cancer. O-linked N-acetylglucosamine transferase (OGT) is a key regulator of glycosylation, and its abnormal expression is associated with various types of cancer. Methods: This study collected the clinical and histopathological data of patients who were diagnosed with pancreatic cancer and underwent surgery in the Affiliated Hospital of Qingdao University from January 2017 to January 2021. Information such as age, gender, Body mass index (BMI), smoking, alcohol consumption, diabetes history, family history, tumor size, location, TNM stage, tissue infiltration and organ metastasis, Carcinoembryonic antigen (CEA) and Carbohydrate antigen19-9 (CA19-9) levels were collected. On this basis, we used immunohistochemical staining to detect the expression levels of OGT in cancer tissues and adjacent normal pancreatic duct tissues, and divided them into high expression group and low expression group according to the expression level, and analyzed their correlation with the clinicopathological characteristics and prognosis of patients. Results: 1) There were statistically significant differences between the expression levels of OGT in pancreatic cancer tissues and those in normal tissues adjacent to the cancer (P < 0.001). 2) High expression of OGT was associated with lymph node metastasis and TNM stage (P < 0.05) and there was no correlation with factors such as age, gender, BMI, smoking, alcohol consumption, history of diabetes mellitus, family
| [1] | Siegel, R.L., Miller, K.D., Wagle, N.S., et al. (2023) Cancer statistics. CA: A Cancer Journal for Clinicians, 73, 17-48. https://doi.org/10.3322/caac.21763 |
| [2] | Kinoshita, R., Ishima, Y., Chuang, V.T.G., et al. (2021) The Therapeutic Effect of Human Serum Albumin Dimer-Doxorubicin Complex against Human Pancreatic Tumors. Pharmaceutics, 13, Article 1209. https://doi.org/10.3390/pharmaceutics13081209 |
| [3] | Pinho, S.S. and Reis, C.A. (2015) Glycosylation in Cancer: Mechanisms and Clinical Implications. Nature Reviews Cancer, 15, 540-555. https://doi.org/10.1038/nrc3982 |
| [4] | Thomas, D., Rathinavel, A.K. and Radhakrishnan, P. (2021) Altered Glycosylation in Cancer: A Promising Target for Biomarkers and Therapeutics. Biochimica et Biophysica Acta (BBA)—Reviews on Cancer, 1875, Article 188464. https://doi.org/10.1016/j.bbcan.2020.188464 |
| [5] | Munkley, J. and Elliott, D.J. (2016) Hallmarks of Glycosylation in Cancer. Oncotarget, 7, 35478-35489. https://doi.org/10.18632/oncotarget.8155 |
| [6] | Bond, M.R. and Hanover, J.A. (2015) A Little Sugar Goes a Long Way: The Cell Biology of O-GlcNAc. Journal of Cell Biology, 208, 869-880. https://doi.org/10.1083/jcb.201501101 |
| [7] | Jiang, K., Gao, Y., Hou, W., et al. (2013) Proteomic Analysis of O-GlcNAcylated Proteins in Invasive Ductal Breast Carcinomas with and without Lymph Node Metastasis. Amino Acids, 48, 365-374. https://doi.org/10.1007/s00726-015-2089-8 |
| [8] | Chaiyawat, P., Chokchaichamnankit, D., Lirdprapamongkol, K., et al. (2015) Alteration of O-GlcNAcylation Affects Serine Phosphorylation and Regulates Gene Expression and Activity of Pyruvate Kinase M2 in Colorectal Cancer Cells. Oncology Reports, 34, 1933-1942. https://doi.org/10.3892/or.2015.4178 |
| [9] | Lin, C.H., Liao, C.C., Wang, S.Y., et al. (2022) Comparative O-GlcNAc Proteomic Analysis Reveals a Role of O-GlcNAcylated SAM68 in Lung Cancer Aggressiveness. Cancers (Basel), 14, Article 243. https://doi.org/10.3390/cancers14010243 |
| [10] | Jang, T.J. and Kim, U.J. (2016) O-GlcNAcylation Is Associated with the Development and Progression of Gastric Carcinoma. Pathology—Research and Practice, 212, 622-630. https://doi.org/10.1016/j.prp.2016.04.002 |
| [11] | Harosh-Davidovich, S.B. and Khalaila, I. (2018) O-GlcNAcylation Affects β-Catenin and E-Cadherin Expression, Cell Motility and Tumorigenicity of Colorectal Cancer. Experimental Cell Research, 364, 42-49. https://doi.org/10.1016/j.yexcr.2018.01.024 |
| [12] | Starska, K., Forma, E., Brzezińska-B？aszczyk, E., et al. (2015) Gene and Protein Expression of O-GlcNAc-Cycling Enzymes in Human Laryngeal Cancer. Clinical and Experimental Medicine, 15, 455-468. https://doi.org/10.1007/s10238-014-0318-1 |
| [13] | Mi, W., Gu, Y., Han, C., et al. (2011) O-GlcNAcylation Is a Novel Regulator of Lung and Colon Cancer Malignancy. Biochimica et Biophysica Acta, 1812, 514-519. https://doi.org/10.1016/j.bbadis.2011.01.009 |
| [14] | Liu, Y., Huang, H., Cao, Y., et al. (2017) Suppression of OGT by microRNA24 Reduces FOXA1 Stability and Prevents Breast Cancer Cells Invasion. Biochemical and Biophysical Research Communications, 487, 755-762. https://doi.org/10.1016/j.bbrc.2017.04.135 |
| [15] | Ning, D., Chen, J., Du, P., et al. (2021) The Crosstalk Network of XIST/miR-424-5p/OGT Mediates RAF1 Glycosylation and Participates in the Progression of Liver Cancer. Liver International, 41, 1933-1944. https://doi.org/10.1111/liv.14904 |
| [16] | Zhang, N., Jiang, H., Zhang, K., et al. (2022) OGT as Potential Novel Target: Structure, Function and Inhibitors. Chemico-Biological Interactions, 357, Article 109886. https://doi.org/10.1016/j.cbi.2022.109886 |
| [17] | Guillaumond, F., Iovanna, J.L. and Vasseur, S. (2014) Pancreatic Tumor Cell Metabolism: Focus on Glycolysis and Its Connected Metabolic Pathways. Archives of Biochemistry and Biophysics, 545, 69-73. https://doi.org/10.1016/j.abb.2013.12.019 |
| [18] | Guillaumond, F., Leca, J., Olivares, O., et al. (2013) Strengthened Glycolysis under Hypoxia Supports Tumor Symbiosis and Hexosamine Biosynthesis in Pancreatic Adenocarcinoma. Proceedings of the National Academy of Sciences of the United States of America, 110, 3919-3924. https://doi.org/10.1073/pnas.1219555110 |
