Expression and clinical significance of UBE2S in gastric cancer
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摘要:
目的 探讨泛素结合酶2S (UBE2S)在胃癌(GC)组织中的表达情况, 并探讨其与GC患者远期预后的关系。 方法 将2016年1月-2016年12月蚌埠医学院第一附属医院胃肠外科收治的GC患者(101例)列为研究对象, 收集所有患者肿瘤组织及临床信息, 通过免疫组织化学法检测癌及癌旁组织中UBE2S蛋白水平, 分析UBE2S与组织病理学检测值之间的关系, 探讨UBE2S表达对GC预后的影响, 绘制生存曲线。利用生物信息学手段分析UBE2S可能参与肿瘤发生的机制。 结果 免疫组化分析显示, UBE2S在GC组织中的表达显著高于癌旁组织, 与组织病理学参数的关系提示UBE2S的阳性表达与CEA、CA19-9、T分期、N分期均明显相关(均P < 0.01), 多因素分析提示UBE2S高表达为GC的独立危险因素(HR=2.832, 95%CI: 1.361~4.170;P < 0.01)。Kaplan-Meier生存曲线显示, GC患者的术后生存率与UBE2S高低表达组别之间差异有统计学意义(log-rank χ2=27.512, P < 0.01), ROC曲线结果显示AUC=0.789, 敏感度和特异度分别为77.42%和74.36%。 结论 UBE2S高表达于GC中, 其与GC预后密切相关, UBE2S高表达可作为影响GC患者术后生存率的独立危险因素。 Abstract:Objective To investigate the expression of ubiquitin-binding enzyme 2S (UBE2S) in gastric cancer (GC) tissues, and to explore its relationship with the long-term prognosis of GC patients. Methods A total of 101 GC patients admitted to Department of Gastrointestinal Surgery, the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2016 were selected as the study subjects.Tumor tissue and clinical information of all patients were collected.UBE2S protein levels in cancer and adjacent tissues were detected by immunohistochemistry, and the relationship between UBE2S and histopathological detection values was analyzed.The effect of UBE2S expression on GC prognosis was investigated and survival curve was drawn.Bioinformatics methods were used to analyze the possible mechanism of UBE2S involved in tumor. Results Immunohistochemical analysis showed that the expression of UBE2S in GC tissues was significantly higher than that in adjacent tissues.The positive expression of UBE2S was significantly correlated with CEA, CA19-9, T stage and N stage (P < 0.01).Multivariate analysis suggested that UBE2S was an independent risk factor for gastric cancer (HR=2.832, 95%CI: 1.361-4.170, P < 0.01).Kaplan-Meier survival curve showed that the postoperative survival rate of GC patients was discrepant from different UBE2S expression (log-rank χ2=27.512, P < 0.01).ROC curve results showed AUC=0.789, sensitivity and specificity were 77.42% and 74.36%, respectively. Conclusion UBE2S is highly expressed in GC, which is closely related to the prognosis of GC.The high expression of UBE2S may be an independent risk factor for postoperative survival in patients with GC. -
Key words:
- UBE2S /
- Gastric cancer /
- Survival analysis /
- Prognosis /
- Bioinformatics
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图 1 GC组织中UBE2S和Ki67的表达情况
注：使用免疫组织化学ABC法检测；A、B为UBE2S在癌旁组织和GC组织中的表达；C、D为Ki67在癌旁组织和GC组织中的表达。
Figure 1. Expression of UBE2S and Ki67 in GC tissues
图 2 UBE2S和Ki67在GC组织中的表达量及相关性
注：A为UBE2S在不同组织的相对表达量，aP < 0.05；B为Ki67在不同组织的相对表达量，aP < 0.05；C为UBE2S与Ki67相关性分析。
Figure 2. Expression levels and correlation of UBE2S and Ki67 in GC tissues
图 3 K-M分析UBE2S相对表达量对GC根治术后5年生存率的影响
Figure 3. The effect of UBE2S relative expression on 5 year survival rate after radical GC operation analyzed by K-M
图 4 UBE2S表达量对GC根治术后5年生存情况的预判价值
Figure 4. Predictive value of UBE2S expression on 5-year survival after radical GC surgery
表 1 GC患者组织中UBE2S的表达与临床及病理特征的关系[例(%)]
Table 1. Relationship between UBE2S expression and clinical and pathological features in GC patients[cases(%)]
因素 例数 UBE2S χ2值 P值 因素 例数 UBE2S χ2值 P值 低表达(n=51) 高表达(n=50) 低表达(n=51) 高表达(n=50) 性别 2.792 0.095 肿瘤大小(cm) 0.308 0.579 男性 76 42(55.3) 34(44.7) ＜5 66 32(48.5) 34(51.5) 女性 25 9(36.0) 16(64.0) ≥5 35 19(54.3) 16(45.7) 年龄(岁) 2.279 0.131 T分期 5.232 0.022 ＜60 39 16(41.0) 23(59.0) 1~2期 54 33(61.1) 21(38.9) ≥60 62 35(56.5) 27(43.5) 3~4期 47 18(38.3) 29(61.7) CEA(μg/L) 8.471 0.004 N分期 8.320 0.004 ＜5 59 37(62.7) 22(37.3) 0~1期 53 34(64.2) 19(35.8) ≥5 42 14(33.3) 28(66.7) 2~3期 48 17(35.4) 31(64.6) CA19-9(kU/L) 9.637 0.002 ＜37 58 37(63.8) 21(36.2) ≥37 43 14(32.6) 29(67.4) 
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表 2 影响GC根治术后5年生存期的单因素及多因素分析
Table 2. Univariate and multivariate analysis of 5-year survival after radical GC surgery
因素 单因素分析 多因素分析 log-rank χ2值 P值 HR值 95% CI P值 性别(男性vs. 女性) 2.140 0.144 年龄(＜60岁vs. ≥60岁) 0.014 0.905 UBE2S(高表达vs. 低表达) 27.512 < 0.001 2.382 1.361~4.170 0.002 CEA水平(＜5 μg/L vs. ≥5 μg/L) 20.601 < 0.001 1.906 1.120~3.242 0.017 CA19-9 (＜37 kU/L vs. ≥37 kU/L) 23.247 < 0.001 1.897 1.084~3.322 0.025 肿瘤大小(＜5 cm vs. ≥5 cm) 0.022 0.883 T分期(T1~2 vs. T3~4) 17.772 0.898 1.940 1.132~3.324 0.016 N分期(N0~1 vs. N2~3) 21.615 < 0.001 1.839 1.027~3.293 0.041 注：各变量赋值方法如下，性别：男性=1，女性=0；年龄：＜60岁=0，≥60岁=1；UBE2S：低表达组=0，高表达组=1；CEA：＜5 μg/L=0，≥5 μg/L=1；CA19-9：＜37 kU/L=1，≥37 kU/L=1；肿瘤大小：＜5 cm=0，≥5 cm=1；T分期：T1~2=0，T3~4=1；N分期：N0~1=0，N2~3=1。
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