目的 探究中心体相关蛋白55（CEP55）、兴奋性氨基酸转运体1（GLAST）在肝细胞癌（HCC）中的表达水平，并分析二者与HCC患者根治性切除术后复发转移的关系。 方法 选择2020年3月~2023年10月我院收治的128例HCC患者，以距肿瘤边缘至少5 cm、无明显肝脏病变的癌旁正常组织为对照，采用免疫组化法检测CEP55、GLAST表达水平。比较癌组织、癌旁正常组织CEP55、GLAST蛋白表达，采用Spearman相关性检验分析CEP55、GLAST蛋白表达与临床病理特征的关系。随访截至2024年10月，出现HCC复发或远处转移的患者纳入复发转移组，未出现复发或转移的患者纳入未复发转移组，比较两组CEP55、GLAST蛋白表达及临床病理特征。采用COX多因素回归分析HCC术后复发转移的风险因素。采用Kaplan-Meier生存分析比较CEP55、GLAST不同表达水平患者的无进展生存期。 结果 128例HCC患者最终纳入120例进行分析。HCC癌组织CEP55蛋白阳性率较癌旁组织高（P<0.05），GLAST蛋白阳性率较癌旁组织低（P<0.05）。Spearman相关分析显示，CEP55阳性表达与年龄、肿瘤直径、肿瘤数量、Child-Pugh分级、巴塞罗那（BCLC）分期、术前甲胎蛋白（AFP）水平均呈正相关（P<0.05），与分化程度均呈负相关（P<0.05）；GLAST阳性表达与年龄、肿瘤直径、肿瘤数量、Child-Pugh分级、BCLC分期、术前AFP水平均呈负相关（P<0.05），与分化程度呈正相关（P<0.05）。120例患者中共有32例术后发生复发转移，发生率为26.67%。复发转移组CEP55蛋白阳性率较未复发转移组高，GLAST蛋白阳性率较未复发转移组低（P<0.05）。多因素COX回归分析显示，CEP55阳性是HCC术后复发转移的危险因素（P<0.05），GLAST阳性是HCC术后复发转移的保护因素（P<0.05）。CEP55、GLAST不同表达水平患者生存时间比较差异均有统计学意义（P=0.000、0.017）。 结论 CEP55和GLAST在HCC组织中的表达水平与HCC患者根治性切除术后复发转移密切相关，CEP55高表达和GLAST低表达可能提示HCC患者复发转移风险升高，并显著缩短无进展生存期。
Abstract
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.
关键词
肝细胞癌 /
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根治性切除术 /
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中心体相关蛋白55 /
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兴奋性氨基酸转运体1 /
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蛋白表达 /
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复发转移
Key words
Hepatocellular carcinoma /
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Radical resection /
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Centrosomal protein 55 /
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Excitatory amino acid transporter 1 /
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Protein expression /
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Recurrence and metastasis
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基金
江苏省卫生健康委科研项目(Z2021088)，南通市基础科学研究计划项目(JCZ21092)
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