肝细胞肝癌中CyclinA1的表达及意义

EXPRESSION AND SIGNIFICANCE OF CYCLINA1 IN HEPATOCELLULAR CARCINOMA

目的 探讨细胞周期蛋白A1(CyclinA1)在肝细胞肝癌(HCC)中的表达及意义。方法 应用实时荧光定量PCR(qRT-PCR)和Western blot方法,分别检测新鲜HCC及相应癌旁非瘤组织中CyclinA1 mRNA和蛋白的表达水平;应用组织芯片及免疫组织化学方法,检测HCC及相应癌旁非瘤石蜡包埋组织中CyclinA1蛋白的表达情况。结果 新鲜HCC组织中CyclinA1 mRNA和蛋白质的表达均明显高于相应癌旁非瘤组织(t=4.739、12.690,P<0.01);HCC石蜡包埋组织中CyclinA1的表达高于癌旁非瘤组织(z=-16.019,P<0.001)。CyclinA1的表达水平与HCC分化程度、TNM分期、肿瘤是否多发、脉管侵犯、被膜侵犯和肿瘤大小有关(χ^(2)=4.559~15.551,P<0.05)。生存分析表明,CyclinA1低表达HCC病人的术后总体和无病生存时间较高表达者更长(χ^(2)=15.060、12.930,P<0.05)。Cox多因素回归分析表明,CyclinA1、分化程度、肿瘤是否多发、肿瘤大小是影响HCC病人术后总体及无病生存时间的独立预后因素(β=-1.379~1.453,HR(95%CI)=0.252(0.145~0.436)~4.274(2.188~8.350),P<0.05)。结论 CyclinA1可能促进HCC发生,并且促进肿瘤的生长及侵袭转移;CyclinA1高表达提示病人预后不良,可作为判断HCC病人预后的潜在分子标志物及潜在治疗靶点。

Objective To investigate the expression and significance of CyclinA1 in hepatocellular carcinoma(HCC).Methods Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expressive levels of CyclinA1 in fresh HCC tissue and adjacent non-tumor tissue, and tissue microarray and immunohistochemistry were used to measure the expression level of CyclinA1 in paraffin-embedded tissue samples of HCC tissue and adjacent non-tumor tissue. Results The mRNA and protein expression levels of CyclinA1 in fresh HCC tissue were significantly higher than those in adjacent non-tumor tissue(t=4.739,12.690;P<0.01), and the expression level of CyclinA1 in paraffin-embedded HCC tissue was significantly higher than that in adjacent non-tumor tissue(z=-16.019,P<0.001). The expression level of CyclinA1 in HCC was associated with degree of tumor differentiation, TNM stage, presence or absence of multiple tumors, angiolymphatic invasion, capsular invasion, and tumor size(χ^(2)=4.559-15.551,P<0.05). Survival analysis showed that the HCC patients with low CyclinA1 expression had significantly longer overall survival(OS) time and disease-free survival(DFS) time than those with high CyclinA1 expression(χ^(2)=15.060,12.930;P<0.05). The multivariate Cox regression analysis showed that CyclinA1 expression, degree of tumor diffe-rentiation, presence or absence of multiple tumors, and tumor size were independent influencing factors for OS and DFS in HCC patients(β=-1.379 to 1.453,HR=0.252-4.274,95%CI:(0.145-0.436) to(2.188-8.350),P<0.05). Conclusion Cyc-linA1 may promote the oncogenesis of HCC and the growth, invasion, and metastasis of tumor. High CyclinA1 expression may suggest poor prognosis, and thus CyclinA1 may be used as a potential biomarker for predicting the prognosis of HCC patients and a potential therapeutic target for HCC patients.