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摘要:
目的 探讨泛素连接酶CUL4A、CUL4B的表达与局限期小细胞肺癌(limited small cell lung cancer, L-SCLC)临床病理特征及预后的关系。 方法 采用组织芯片技术及免疫组织化学Envision二步法检测72例L-SCLC组织和14例L-SCLC癌旁组织CUL4A、CUL4B的表达情况。 结果 CUL4A在L-SCLC组织中的阳性率为72.2%(52/72), 显著高于癌旁组织中的阳性率35.7%(5/14)(P < 0.05)。CUL4A的表达与患者吸烟情况密切相关(P < 0.05), 而与性别、年龄、肿瘤大小、淋巴结是否转移、胸膜侵袭、血小板(PLT)和乳酸脱氢酶(LDH)无显著相关性(P > 0.05)。CUL4B在L-SCLC组织中的阳性率分为68.1%(49/72), 显著高于癌旁组织中的阳性率28.6%(4/14)(P < 0.05), CUL4B的表达与患者性别、吸烟情况密切相关(P < 0.05), 而与年龄、肿瘤大小、淋巴结是否转移、胸膜侵袭、PLT升高和LDH升高无显著相关性(P > 0.05)。单因素分析发现, 淋巴结是否转移、CUL4A表达水平、CUL4B表达水平和血液LDH量均与患者的中位无病进展时间(progression-free survival, PFS)和中位生存时间(overall survival, OS)密切相关。多因素结果显示, CUL4B高表达是影响OS的独立危险因素, 而淋巴结转移、血液LDH升高不仅是影响OS, 也是影响PFS的独立危险因素。 结论 CUL4过表达可能是局限期小细胞肺癌发展过程中一个重要的环节, 可以作为预测局限期小细胞肺癌预后的参考指标之一, 并为局限期小细胞肺癌的靶向治疗提供依据。 Abstract:Objective This study aims to investigate the expression levels of CUL4A and CUL4B in limited small cell lung cancer(L-SCLC) and to explore its relationship with clinicopathologic characteristics and clinical outcomes of L-SCLC. Methods The expression levels of CUL4A and CUL4B were detected immunohistochemically in 72 cases of L-SCLC tissues and 14 cases of para-cancerous tissues in tissue microarrays. Results The positive rate of CUL4A was significantly higher in L-SCLC tissues(72.2%)52/72, than in para-cancerous tissues(35.7%5/14;P < 0.05).The expression level of CUL4A was closely related to smoking history(P < 0.05) but not to gender, age, primary tumor size, lymph node status, pleura invasion status, platelet(PLT) count, and lactate dehydrogenase(LDH) activity(P > 0.05).The positive rate of CUL4B was significantly higher in L-SCLC tissues(68.1%49/72) than in para-cancerous tissues(28.6%4/14;P < 0.05).The expression of CUL4B was closely related to gender and smoking history(P < 0.05) but not to age, primary tumor size, lymph node status, pleura invasion status, PLT count, and LDH activity(P > 0.05).In univariate analysis, lymph node status, CUL4A, CUL4B, and LDH were related to progression-free survival(PFS) and overall survival(OS).Multivariate analysis revealed that CUL4B independently influenced OS.However, lymph node status and LDH were independent risk factors of both PFS and OS. Conclusion CUL4 may be a critical factor in L-SCLC progression.Thus, it could be a novel potential bio-marker that can predict the prognosis of L-SCLC and allow for targeted therapeutics. -
Key words:
- limited small cell lung cancer /
- ubiquitin ligases /
- CUL4
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图 1 CUL4A和CUL4B在局限期小细胞肺癌组织和癌旁组织中的表达情况(DAB, ×400)
Figure 1. CUL4A and CUL4B expression in L-SCLC tissues and pa-ra-cancerous tissues(×400)
A: The expression of CUL4A in L-SCLC tissues and para-cancerous tissues; B: The expression of CUL4B in L-SCLC tissues and para-cancerous tissues
图 3 CUL4A低表达组与高表达组的总生存曲线
Figure 3. OS curve of low CUL4A expression group and high CUL4A ex-pression group
图 4 CUL4B低表达组与高表达组的总生存曲线
Figure 4. OS curve of low CUL4B expression group and high CUL4B ex-pression group
表 1 CUL4表达与局限期小细胞肺癌临床病理参数间的关系
Table 1. Association of CUL4 with clinicopathologic characteristics of L-SCLC
表 2 局限期小细胞肺癌患者预后影响因素的单因素分析
Table 2. Univariate analysis of clinical characteristics and survival in L-SCLC
表 3 局限期小细胞肺癌患者预后影响因素的多因素分析
Table 3. Multivariate analysis of clinical characteristics and survival in L-SCLC
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