生存素与细胞分裂周期相关蛋白5在胃癌及胃间质瘤中的表达及其临床意义

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摘要目的：检测生存素与细胞分裂周期相关蛋白5(cell division cycle associated protein 5，CDCA5)在胃癌及胃间质瘤中的表达，分析两者相关性及其对临床病理学参数的评估价值。方法：首先通过GEPIA数据库分析生存素的编码基因BIRC5 mRNA与CDCA5 mRNA在胃癌中的表达及相关性；采用免疫组化检测76例胃癌和63例胃间质瘤中生存素与CDCA5表达，应用Spearman相关检验分析两者相关性，并分析其与患者临床病理特征的相关性。接着，通过PROMO数据库分析可能作用于BIRC5与CDCA5启动子的转录因子。最后，利用HDOCK预测生存素与CDCA5的相互作用。结果： GEPIA数据库分析显示，BIRC5 mRNA和CDCA5 mRNA在胃癌组织中表达均明显高于正常胃组织(P<0.01)，且两者在胃癌组织中的表达呈正相关(r=0.79，P<0.01)；免疫组化结果显示，在胃癌和胃间质瘤中，生存素与CDCA5均在细胞核与细胞质中表达，两者表达量均明显高于对应癌旁/瘤旁组织(P均<0.001)，且两者在胃癌、胃间质瘤组织中的表达呈一定的正相关(r胃癌=0.410，r胃间质瘤=0.347，P均<0.05)。胃癌中，生存素与肿瘤直径、淋巴管侵犯及TNM分期相关(P<0.05)；CDCA5表达与肿瘤分化程度、TNM分期相关(P<0.05)；两者共阳性表达与肿瘤直径、肿瘤分化程度、淋巴管侵犯及TNM分期相关(P<0.05)。胃间质瘤中，生存素与核分裂象及NIH危险度分级相关(P<0.05)；CDCA5与肿瘤直径及NIH危险度分级相关(P<0.05)；两者共阳性表达与肿瘤直径、核分裂象及NIH危险度分级相关(P<0.05)。另外，PROMO发现有13个转录因子可同时调控CDCA5与BIRC5启动子；HDOCK预测发现，生存素蛋白与CDCA5蛋白之间存在多对相互作用。结论：在多种转录因子的共同作用下，生存素与CDCA5在胃癌与胃间质瘤中均呈高表达，且呈正相关；两者均与胃癌、胃间质瘤的部分临床病理学参数相关，且联合检测临床价值大于单个分子的检测。

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	包洁1
	高小姣2
	韩玮3
	王庆华1

关键词 ：胃癌font-family: ????, font-weight: 700, text-align: -webkit-right, ')" href="#">background-color: rgb(212, 226, 255);">, 胃间质瘤font-family: ????, font-weight: 700, text-align: -webkit-right, ')" href="#">background-color: rgb(212, 226, 255);">, 生存素font-family: ????, font-weight: 700, text-align: -webkit-right, ')" href="#">background-color: rgb(212, 226, 255);">, 细胞分裂周期相关蛋白5

Abstract： Objective： To detect the expression of survivin and cell division cycle associated protein 5 (CDCA5) in gastric cancer and gastric stromal tumor, and analyze the correlation between them and their value in the evaluation of clinicopathological parameters. Methods： Firstly, the expression and correlation of survivin coding gene, BIRC5 (baculoviral IAP repeat containing 5) and CDCA5 in gastric cancer were analyzed by GEPIA database. Immunohistochemistry was used to detect the expression of survivin and CDCA5 in 76 cases of gastric cancer and 63 cases of gastric stromal tumor. Spearman′s rank correlation test was used to analyze the correlation between survivin and CDCA5 and clinicopathological features of the patients. Then, PROMO database was used to predict transcription factors that may act on their promoters. Finally, the interaction between survivin and CDCA5 was predicted by HDOCK. Results： GEPIA database analysis showed that the expressions of BIRC5 mRNA and CDCA5 mRNA in gastric cancer tissues were significantly higher than those in normal gastric tissues (P<0.01), and the expressions of BIRC5 mRNA and CDCA5 mRNA in gastric cancer tissues were positively correlated (r=0.79, P<0.01). Immunohistochemical results showed that the expression levels of survivin and CDCA5 were significantly higher than those of the corresponding paracancerous/paratumoral tissues (P<0.001), and the expressions of both were positively correlated in gastric cancer and gastric stromal tumor tissues (rgastric cancer=0.410，rgastric stromal tumor=0.347，both P<0.05). In gastric cancer, survivin was positively correlated with tumor size, lymphatic vessel invasion and TNM stage (all P<0.05); CDCA5 expression was negatively correlated with tumor differentiation (P<0.05) and positively correlated with TNM stage (P<0.05); and the copositive expression was closely related to tumor size, tumor differentiation lymphatic vessel invasion and TNM stage (all P<005). In gastric stromal tumors, survivin was positively correlated with mitosis and National Institute of Health (NIH) risk stratifications (P<0.05); CDCA5 was positively correlated with tumor size and NIH risk stratifications (P<0.05); and the copositive expression was positively correlated with tumor size, mitosis and NIH risk stratifications (P<0.05). In addition, PROMO identified 13 transcription factors that might regulate CDCA5 and BIRC5 promoters simultaneously. And HDOCK predicted that there were multiple pairs of interactions between survivin and CDCA5. Conclusion： Under the co-action of multiple transcription factors, survivin and CDCA5 were up-regulated in gastric cancer and gastric stromal tumour with a positive correlation. Both were related to some clinicopathological parameters of gastric cancer and gastric stromal tumor, and the clinical value of combined detection is greater than that of individual molecular detection.

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收稿日期: 2022-08-28

基金资助: 2018年昆山市市级科技专项(KS1872)；2018年江苏大学医学临床科技发展基金项目(JLY20180107)

通讯作者: 王庆华(通讯作者)，副主任医师，E-mail: ksph_wqh@sina.com

作者简介: 包洁(1980—)，女，硕士，副主任医师，主要从事消化道疾病的研究；

引用本文:

包洁1，高小姣2，韩玮3，王庆华1. 生存素与细胞分裂周期相关蛋白5在胃癌及胃间质瘤中的表达及其临床意义[J]. 江苏大学学报:医学版, 2024, 24(01): 11-18. BAO Jie1, GAO Xiaojiao2, HAN Wei3, WANG Qinghua1. Expression and clinical significance of survivin and cell division cycle associated protein 5 in gastric cancer and gastric stromal tumor. Journal of Jiangsu University(Medicine Edition), 2024, 24(01): 11-18.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2024/V24/I01/11

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