Expression of ITGB2 in gastric cancer and its clinical value
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摘要:
目的 探究ITGB2在胃癌组织中的表达情况及其与胃癌恶性进展的相关性，并利用生物信息学分析ITGB2可能参与的生物学过程。 方法 利用在线数据库分析ITGB2在胃癌组织中的表达水平以及与胃癌恶性进展之间的相关性。纳入2016年2月—2018年12月于蚌埠医科大学第一附属医院接受胃癌根治术的107例胃癌患者。分析ITGB2在胃癌组织中的表达情况及其对胃癌患者预后的影响。采用DAVID数据库分析ITGB2可能参与的生物学过程和信号通路。运用TIMER2.0数据库探究ITGB2表达量与多种免疫细胞浸润的潜在联系。 结果 免疫组化结果显示，ITGB2在胃癌组织中高表达(胃癌组织表达量3.465±1.037，癌旁组织表达量1.000±0.271，t=22.653，P＜0.001)。qRT-PCR实验结果验证ITGB2的mRNA水平在胃癌组织中高于癌旁组织(P＜0.001)。Western blotting实验进一步验证了以上实验结果。ITGB2高表达组患者生存率低于ITGB2低表达组(log-rank χ2=38.394，P＜0.001)。单因素及多因素分析显示胃癌组织中ITGB2高表达、外周血中CEA≥5 μg/L、CA19-9≥37 kU/L、临床T3~T4期及N2~N3期(P＜0.05)是影响胃癌患者预后的独立危险因素。生物信息学分析显示ITGB2参与的生物过程主要涉及免疫反应的调节。 结论 ITGB2在胃癌中呈高表达并参与胃癌恶性演进，与胃癌患者的预后不良及免疫细胞浸润密切相关。 Abstract:Objective To investigate the expression of ITGB2 in gastric cancer tissues and its correlation with malignant progression of gastric cancer, and to analyze the possible biological processes of ITGB2 by bioinformatics. Methods The expression level of ITGB2 in gastric cancer tissues and its correlation with malignant progression of gastric cancer were analyzed using online database. A total of 107 patients with gastric cancer who received radical gastrectomy in the First Affiliated Hospital of Bengbu Medical University from February 2016 to December 2018 were included. The expression of ITGB2 in gastric cancer tissues and its effect on the prognosis of patients with gastric cancer were analyzed. The biological processes and signaling pathways involved in ITGB2 were analyzed using DAVID database. TIMER2.0 database was used to explore the potential relationship between ITGB2 expression and various immune cell infiltration. Results Immunohistochemical results showed that ITGB2 was highly expressed in gastric cancer tissues (3.465±1.037 in gastric cancer tissues and 1.000±0.271 in para-cancerous tissues, t=22.653, P < 0.001). The results of qRT-PCR test confirmed that the mRNA level of ITGB2 in gastric cancer tissue was significantly higher than that in paracancer tissue (P < 0.001). Western blotting test further verified the above experimental results. The survival rate of patients with high ITGB2 expression group was lower than that of patients with low ITGB2 expression group (log-rank χ2=38.394, P < 0.001). Univariate and multivariate analysis showed that high expression of ITGB2 in gastric cancer tissue, CEA≥5 μg/L in peripheral blood, CA19-9≥37 kU/L, clinical T3-T4 and N2-N3 (P < 0.05) were independent risk factors affecting the prognosis of patients with gastric cancer. Bioinformatic analysis showed that ITGB2 was involved in the regulation of immune response. Conclusion ITGB2 is highly expressed in gastric cancer and is involved in the malignant evolution of gastric cancer, which is closely related to the poor prognosis and immune cell infiltration of patients with gastric cancer. -
Key words:
- Gastric cancer /
- Prognosis /
- ITGB2 /
- Immune infiltration
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图 1 基于公共数据库分析ITGB2在胃癌中的表达水平
注：A为ITGB2在泛癌中的表达情况；B、C为公共数据库分析ITGB2在胃癌中的表达情况。
Figure 1. Analysis of ITGB2 expression levels in gastric cancer based on public databases
图 2 人体组织学分析ITGB2在胃癌中的表达水平
注：A、B为免疫组化检测分析ITGB2的表达水平；C~E为PCR及Western blotting分析ITGB2的表达水平；aP<0.001。
Figure 2. Expression level of ITGB2 in gastric cancer through the body histological analysis
图 3 ITGB2表达水平与胃癌恶性进展的关系
注：A为ITGB2表达水平与胃癌分级的关系；B为ITGB2表达水平与胃癌淋巴结转移的关系；C为ITGB2表达水平与胃癌分期的关系。
Figure 3. Relationship between the expression level of ITGB2 and the malignant progression of gastric cancer
图 4 ITGB2表达量对胃癌患者预后的影响
注：A为公共数据库分析ITGB2表达与患者生存期的关系；B为基于本机构临床数据分析ITGB2表达水平对胃癌患者术后5年生存率的影响；C为基于本机构临床数据分析得到的ROC生存曲线。
Figure 4. Effect of ITGB 2 expression on prognosis of gastric cancer patients
图 5 GO和KEGG分析ITGB2可能参与的生物学途径
注：A为ITGB2的GO富集分析；B为ITGB2的KEGG富集分析。
Figure 5. Analysis of possible biological pathways of ITGB2 by GO and KEGG
表 1 ITGB2表达与临床病理参数间的关系(例)
Table 1. Relationship between ITGB2 expression and clinicopathological parameters (cases)
项目 例数 ITGB2 χ2值 P值 高表达(n=53) 低表达(n=54) 性别 0.097 0.755 女性 44 21 23 男性 63 32 31 年龄 2.112 0.146 ＜60岁 45 26 19 ≥60岁 62 27 35 CEA 26.247 ＜0.001 ＜5 μg/L 52 39 13 ≥5 μg/L 55 14 41 CA19-9 11.444 ＜0.001 ＜37 kU/L 53 35 18 ≥37 kU/L 54 18 36 肿瘤大小 7.941 ＜0.001 ＜5 cm 46 30 16 ≥5 cm 61 23 38 病例分型 0.981 0.322 腺癌 89 46 43 其他 18 7 11 T分期 17.409 ＜0.001 T1~T2 57 39 18 T3~T4 50 14 36 N分期 20.688 ＜0.001 N0~N1 55 39 16 N2~N3 52 14 38 
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表 2 胃癌患者预后的影响因素分析
Table 2. Prognostic factors in patients with gastric cancer
变量 单因素分析 多因素分析 log-rank χ2 P值 HR值 95% CI P值 性别(男性vs. 女性) 0.244 0.621 - - - 年龄(＜60岁vs. ≥60岁) 0.147 0.702 - - - ITGB2表达(低表达vs. 高表达) 38.394 ＜0.001 2.312 1.085~4.924 0.030 CEA(＜5 μg/L vs. ≥5 μg/L) 26.237 ＜0.001 2.458 1.231~4.910 0.011 CA19-9(＜37 kU/L vs. ≥37 kU/L) 16.409 ＜0.001 2.109 1.142~3.894 0.017 病理类型(腺癌vs. 其他) 0.195 0.658 - - - 肿瘤大小(＜5 cm vs. ≥5 cm) 5.863 0.015 0.881 0.464~1.675 0.700 T分期(T1~T2 vs. T3~T4) 17.473 ＜0.001 1.832 1.012~3.316 0.045 N分期(N0~N1 vs. N2~N3) 24.081 ＜0.001 2.015 1.062~3.822 0.032 注：“-”为未纳入分析。
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