Objective To investigate the expression levels of centrosomal protein 55 (CEP55) and excitatory amino acid transporter 1 (GLAST) in hepatocellular carcinoma (HCC), and to analyze the relationship between them and recurrence and metastasis in patients with HCC after radical resection. Methods A total of 128 patients with HCC admitted to the hospital from March 2020 to October 2023 were selected. Normal tissues adjacent to the tumor with a distance of at least 5 cm from the tumor edge were collected as control. Immunohistochemistry was used to detect the expression levels of CEP55 and GLAST. The expression of CEP55 and GLAST proteins in cancer tissues and adjacent normal tissues was compared. Spearman correlation analysis was used to analyze the relationship between CEP55 and GLAST protein expression and clinicopathological characteristics. As of October 2024, patients with recurrence or distant metastasis were included in the recurrence and metastasis group. Those without recurrence or metastasis were included in the non-recurrence and metastasis group. The expression of CEP55 and GLAST protein and clinicopathological characteristics of the two groups were compared. Risk factors for recurrent metastasis after HCC were analyzed by using COX multifactorial regression. Kaplan-Meier survival analysis was used to analyze progression-free survival of patients with different expression levels of CEP55 and GLAST. Results Finally, 120 cases were included in the study. The positive rate of CEP55 protein in cancer tissues was higher than that in adjacent tissues, and the positive rate of GLAST protein was lower than that in adjacent tissues (P<0.05). Spearman correlation analysis showed that CEP55 expression was positively correlated with age, tumor diameter, number of tumors, Child-Pugh grading, Barcelona Clinic Liver Cancer (BCLC) staging and preoperative alpha fetoprotein (AFP) level (P<0.05), and negatively correlated with differentiation degree (P<0.05). GLAST expression was negatively correlated with age, tumor diameter, number of tumors, Child-Pugh grade, BCLC stage and preoperative AFP level (P<0.05), and positively correlated with differentiation degree (P<0.05). Among the 120 patients, 32 patients experienced postoperative recurrence and metastasis, with an incidence rate of 26.67%. The CEP55 protein positivity rate in the recurrent metastasis group was higher than that in the non-recurrent metastasis group (P<0.05), and the GLAST protein positivity rate was lower than in the non-recurrent metastasis group (P<0.05). Multifactorial COX regression analysis showed that CEP55 positivity was a risk factor for recurrent metastasis after HCC surgery (P<0.05) and GLAST positivity was a protective factor for recurrent metastasis after HCC surgery (P<0.05). There were statistically significant differences in survival time among patients with different expression levels of CEP55 and GLAST (P=0.000, 0.017). Conclusions The expression levels of CEP55 and GLAST in HCC tissues are closely related to recurrence and metastasis of HCC after radical resection. High expression of CEP55 and low expression of GLAST may indicate an increased risk of recurrence and metastasis in patients with HCC, and significantly shorten progression-free survival.
Key words
Hepatocellular carcinoma /
  /
  /
Radical resection /
  /
  /
Centrosomal protein 55 /
  /
  /
Excitatory amino acid transporter 1 /
  /
  /
Protein expression /
  /
  /
Recurrence and metastasis
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Chidambaranathan-Reghupaty S, Fisher PB, Sarkar D. Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification[J]. Adv Cancer Res,2021,149:1-61. DOI:10.1016/bs.acr.2020.10.001.
[2] Foglia B, Turato C, Cannito S. Hepatocellular Carcinoma: Latest Research in Pathogenesis, Detection and Treatment[J]. Int J Mol Sci,2023,24(15):12224. DOI:10.3390/ijms241512224.
[3] 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. DOI:10.3322/caac.21660.
[4] 谢亚明, 梁磊, 肖遵强, 等. Naples预后评分对肝细胞癌患者肝切除术后预后的影响[J]. 中华肝胆外科杂志, 2024, 30(5):341-346. DOI:10.3760/cma.j.cn113884-20240111-00009.
[5] Zhang X, Wang DJ, Jia L, et al. N6-methyladenosine-mediated LINC01087 promotes lung adenocarcinoma progression by regulating miR-514a-3p to upregulate centrosome protein 55[J]. Kaohsiung J Med Sci, 2024, 40(9): 801-818. DOI:10.1002/kjm2.12879.
[6] 段金炜. 蛛网膜下腔注射Plv-UbC-HPPE/HEK293细胞对骨癌痛大鼠行为学以及脊髓背角GLAST的影响[D]. 山西:山西医科大学, 2012. DOI:10.7666/d.y2127533.
[7] 中华人民共和国卫生和计划生育委员会医政医管局. 原发性肝癌诊疗规范(2017年版)[J]. 中华消化外科杂志, 2017, 16(7): 635-647. DOI:10.3760/cma.j.issn.1673-9752.2017.07.001.
[8] 俞建达, 陈志坚, 林泽润, 等. 肿瘤负荷评分在预测肝癌根治性切除术后复发中的应用[J]. 中华肝胆外科杂志, 2024, 30(10):727-732. DOI:10.3760/cma.j.cn113884-20240401-00092.
[9] Torimura T, Iwamoto H. Treatment and the prognosis of hepatocellular carcinoma in Asia[J]. Liver Int, 2022,42(9):2042-2054. DOI:10.1111/liv.15130.
[10]买尔旦·赛力木, 阿里旦·艾尔肯, 柯于必, 等. 晚期糖基化终末产物受体对原发性肝癌患者根治术后复发转移及死亡的预测价值[J]. 中华实用诊断与治疗杂志, 2022, 36(1):22-26. DOI:10.13507/j.issn.1674-3474.2022.01.006.
[11]Wang G, Chen B, Su Y, et al. CEP55 as a Promising Immune Intervention Marker to Regulate Tumor Progression: A Pan-Cancer Analysis with Experimental Verification[J]. Cells, 2023,12(20):2457. DOI:10.3390/cells12202457.
[12]Hamed KA, El-Fiky SA, M Gawish A, et al. Assessing the Efficacy of Fenugreek Saponin Nanoparticles in Attenuating Nicotine-Induced Hepatotoxicity in Male Rats[J]. ACS Omega, 2023, 8(45):42722-42731. DOI:10.1021/acsomega.3c05526.
[13]Zhou ZX, Xu LJ, Wang HN, et al. EphA4/ephrinA3 reverse signaling mediated downregulation of glutamate transporter GLAST in Müller cells in an experimental glaucoma model[J]. Glia, 2023, 71(3):720-741. DOI:10.1002/glia.24307.
[14]田祯, 庄皓冉, 江楚雯, 等. YAP通过调控EEF1A2的表达促进肝癌细胞的迁移和侵袭[J]. 南京医科大学学报(自然科学版), 2023, 43(1):8-16. DOI:10.7655/NYDXBNS20230102.
[15]Espírito-Santo S, Coutinho VG, Dezonne RS, et al. Astrocytes as a target for Nogo-A and implications for synapse formation in vitro and in a model of acute demyelination[J]. Glia, 2021, 69(6):1429-1443. DOI:10.1002/glia.23971.
[16]王建峰, 王军, 高姗, 等. 老年原发性肝癌患者癌组织中FoxO1、SREBP2及中心体蛋白55表达特点及意义[J]. 中国老年学杂志, 2023, 43(10): 2357-2360. DOI:10.3969/j.issn.1005-9202.2023.10.016.
[17]徐亚丹, 王飞航, 陈凯玲, 等. 基于术前临床及超声特征的预测肝细胞癌切除术后复发的列线图模型构建[J]. 中华肝胆外科杂志, 2024, 30(8):566-571. DOI:10.3760/cma.j.cn113884-20240418-00110.
[18]Tang Y, Thiess L, Weiler SME, et al. α-catenin interaction with YAP/FoxM1/TEAD-induced CEP55 supports liver cancer cell migration[J]. Cell Commun Signal, 2023, 21(1):162. DOI:10.1186/s12964-023-01169-2.
[19]董雪莲, 王建宇, 邹小云. CEP55蛋白在原发性肝细胞癌组织中的表达与临床特征及预后的相关性分析[J]. 标记免疫分析与临床, 2021, 28(11):1898-1904,1945. DOI:10.11748/bjmy.issn.1006-1703. 2021. 11.019.
[20]沈晨, 张景, 马鹏飞, 等. HBV相关肝细胞癌组织GLAST、GS蛋白表达及其与切除术后早期复发转移的关系[J]. 东南大学学报(医学版), 2024, 43(2):236-242. DOI:10.3969/j.issn.1671-6264.2024.02.012.