E3泛素连接酶Cbl家族在子宫颈鳞状细胞癌中的表达及临床意义
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南通市卫健委面上项目(MB2020019)


Expression and clinical significance of E3 ubiquitin ligase Cbl family in cervical squamous cell carcinoma
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    摘要:

    目的:探讨Casitas B细胞淋巴瘤(Casitas B-lineage lymphoma,Cbl)蛋白家族在子宫颈鳞状细胞癌(cervical squamous cell carcinoma,CSCC)中的表达及临床意义。方法:利用免疫组化法检测114例CSCC中c-Cbl、Cbl-b和Cbl-c的表达情况,分析c-Cbl、Cbl-b和Cbl-c表达水平与CSCC患者临床病理特征、无瘤生存期(disease free survival,DFS)和总生存期(overall survival, OS)的关系。结果:114例CSCC患者中,c-Cbl高表达87例,低表达27例;Cbl-b高表达69例,低表达45例;Cbl-c高表达55例,低表达59例。c-Cbl在癌组织和癌旁鳞状上皮组织化学评分(histochemistry score,H-score)分别为143.80 ± 8.76、95.13 ± 6.54,其在癌组织中的表达高于癌旁鳞状上皮(P < 0.001);Cbl-b在癌组织和癌旁鳞状上皮H-score分别为83.95 ± 5.28、93.54 ± 3.91,其在癌和癌旁鳞状上皮中的表达无差异(P=0.146);Cbl-c在癌组织和癌旁鳞状上皮H-score分别为83.62 ± 6.34、36.54 ± 4.64,其在癌组织中的表达高于癌旁鳞状上皮(P < 0.001)。c-Cbl在高~中分化以及最大径 < 4 cm肿瘤中表达较高(P均 < 0.05),但 c-Cbl表达与患者年龄、脉管侵犯、浸润深度、淋巴结转移以及FIGO分期无关(P均 > 0.05)。Cbl-b在浸润深度 > 2/3纤维肌层患者中表达较高(P=0.045),但 Cbl-b 表达与患者年龄、脉管侵犯、肿瘤分化、肿瘤最大径、淋巴结转移以及 FIGO 分期无关(P均 > 0.05)。 Cbl-c在低分化肿瘤中表达较高(P=0.012),但Cbl-c表达与患者年龄、脉管侵犯、浸润深度、肿瘤最大径、淋巴结转移以及FIGO分期无关(P均 > 0.05)。Kaplan-Meier生存分析显示:c-Cbl高表达患者比低表达患者的DFS和OS长(P均 < 0.05);Cbl-b以及Cbl-c表达与患者的DFS和OS均无关(P均 > 0.05)。Cox单因素和多因素分析显示:c-Cbl表达是影响DFS的独立预后因素(P=0.042); c-Cbl表达是影响OS的相关因素,但不是OS的独立预后因素(P=0.096)。结论:c-Cbl高表达CSCC患者比低表达患者的DFS和 OS延长;c-Cbl表达是影响DFS的独立预后因素,但不是OS的独立预后因素。Cbl-b以及Cbl-c表达与CSCC患者的DFS和OS 均无关。检测c-Cbl的表达状态可为预测CSCC患者的预后提供参考。

    Abstract:

    Objective:To investigate the expression and clinical significance of Casitas B-lineage lymphoma(Cbl)protein family in cervical squamous cell carcinoma(CSCC). Methods:Immunohistochemistry was used to detect the expression of c-Cbl,Cbl-b,and Cbl-c in 114 cases of CSCC. The correlations between c-Cbl,Cbl-b,and Cbl-c expression and clinicopathological characteristics,disease free survival(DFS)and overall survival(OS)were analyzed. Results:Of the 114 CSCC patients,87 had high c-Cbl expression and 27 had low c-Cbl expression;69 had high Cbl-b expression and 45 had low Cbl-b expression;55 had high Cbl-c expression and 59 had low Cbl-c expression. The histochemistry score(H - score)of c -Cbl in CSCC tissues and the adjacent normal tissues was 143.80 ± 8.76 and 95.13 ± 6.54,respectively. c-Cbl expression was increased in CSCC compared with the adjacent normal tissues(P < 0.001). The H-score of Cbl-b in CSCC tissues and the adjacent normal tissues was 83.95 ± 5.28 and 93.54 ± 3.91,respectively. There was no significant difference in Cbl-b expression between CSCC tissues and the adjacent normal tissues(P=0.146). The H-score of Cbl-c in CSCC tissues and the adjacent normal tissues was 83.62 ± 6.34 and 36.54 ± 4.64,respectively. Cbl-c expression was increased in CSCC compared with the adjacent normal tissues(P < 0.001). c-Cbl expression was higher in highly to moderately differentiated tumors and tumors with a maximum diameter less than 4 cm(both P < 0.05),but it was not related to the patient’s age,vascular invasion,depth of invasion, lymph node metastasis and FIGO stage(all P >0.05). Cbl - b expression was higher in patients with invasion depth > 2/3 of fibromuscular layer(P=0.045),but it was not related to patient’s age,vascular invasion,tumor differentiation,maximum tumor diameter,lymph node metastasis and FIGO stage(all P > 0.05). Cbl-c expression was higher in poorly differentiated tumors(P=0.012), but it was not related to patient’s age,vascular invasion,depth of invasion,maximum tumor diameter,lymph node metastasis and FIGO stage(all P > 0.05). Kaplan - Meier survival analysis showed that patients with high c - Cbl expression had prolonged DFS and OS compared with those with low c-Cbl protein expression(both P < 0.05). However,the expression levels of Cbl-b and Cbl-c were not related to DFS and OS(P > 0.05). Cox univariate and multivariate analysis showed that c - Cbl expression was an independent prognostic factor for DFS(P=0.042). c -Cbl was a factor affecting OS,but not an independent prognostic factor for OS in CSCC(P= 0.096). Conclusion:Patients with high c -Cbl expression have prolonged DFS and OS compared with those with low c -Cbl protein expression. c-Cbl expression is an independent prognostic factor for DFS,but not an independent prognostic factor for OS in CSCC. The expression levels of Cbl-b and Cbl-c are not related to DFS and OS in CSCC. Detection of the expression status of c-Cbl may provide a reference for predicting the prognosis of CSCC patients.

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张邢松,沈蓉,朱兴华,缪小兵. E3泛素连接酶Cbl家族在子宫颈鳞状细胞癌中的表达及临床意义[J].南京医科大学学报(自然科学版),2023,(1):34-39

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  • 在线发布日期: 2023-01-17
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