SRGAP1在卵巢癌中的表达及对预后判断的意义

doi:10.12280/gjfckx.20220152

摘要/Abstract

摘要：

目的: 探讨Slit-Robo GTP 酶激活蛋白1（Slit-Robo GTPase-activating protein 1,SRGAP1）在卵巢癌中表达的临床意义。方法: 采用免疫组织化学法分析SRGAP1蛋白在卵巢良性囊肿组织、卵巢癌组织及腹膜转移组织中的表达差异,并通过蛋白质印迹（Western blotting）和实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction,qRT-PCR）技术验证。评估SRGAP1与卵巢癌患者的临床病理参数[年龄、国际妇产科联盟（The International Federation of Gynecology and Obstetrics,FIGO）分期、组织学分型、病理学分级及淋巴结转移]的关系;采用Kaplan Meier plotter分析SRGAP1 mRNA表达水平与患者预后的相关性。结果: 卵巢癌组织中SRGAP1表达高于卵巢良性囊肿组织和腹膜转移组织（P<0.05）。SRGAP1高表达和低表达患者的组织学分型和病理学分级差异有统计学意义（P<0.05）;与SRGAP1低表达患者相比,SRGAP1高表达患者的总生存期（OS）和无进展生存期（PFS）明显缩短,差异有统计学意义（P<0.001）,进展后生存期（PPS）缩短,但差异无统计学意义（P=0.054）。结论: SRGAP1在卵巢癌中表达上调,其高表达与卵巢癌的不良预后有关,可考虑作为卵巢癌预后不良的特异性标志物。

关键词: GTP酶激活蛋白质类, 卵巢肿瘤, 卵巢囊肿, 免疫组织化学, 预后

Abstract:

Objective: To investigate the clinical significance of the expression of Slit-Robo GTPase-activating protein 1 (SRGAP1) in ovarian cancer. Methods: The expression of SRGAP1 protein in benign ovarian cyst tissues, ovarian cancer tissues and peritoneal metastasis tissues was analyzed by immunohistochemistry. The results were verified by Western blotting and quantitative real-time PCR (qRT-PCR). The relationship between SRGAP1 and clinicopathological parameters (age, FIGO stage, histological type, pathological grade and lymph node metastasis) in patients with ovarian cancer was analyzed. Kaplan Meier plotter analyzed the correlation between SRGAP1 mRNA expression level and patient prognosis. Results: The expression of SRGAP1 in ovarian cancer tissues was higher than that in benign ovarian cyst tissues and peritoneal metastasis tissues (P<0.05). There were significant differences in histological types and pathological grades among high and low SRGAP1 expression(P<0.05). Compared with patients with low SRGAP1 expression, patients with high SRGAP1 expression had significantly shorter overall survival (OS) and progression-free survival (PFS), with statistically significant differences (P<0.001), while patients with high SRGAP1 expression had shorter progression-free survival (PPS), with no statistically significant difference (P=0.054). Conclusions: SRGAP1 expression is up-regulated in ovarian cancer, and its high expression is associated with poor prognosis of ovarian cancer, which can be considered as a specific marker of poor prognosis of ovarian cancer.

Key words: GTPase-activating proteins, Ovarian neoplasms, Ovarian cysts, Immunohistochemistry, Prognosis

谢玮薇, 汪希鹏. SRGAP1在卵巢癌中的表达及对预后判断的意义[J]. 国际妇产科学杂志, 2022, 49(3): 307-312.

XIE Wei-wei, WANG Xi-peng. Expression of SRGAP1 in Ovarian Cancer and Its Significance in Prognosis[J]. Journal of International Obstetrics and Gynecology, 2022, 49(3): 307-312.

图/表 4

表1 引物序列表

基因		序列
SRGAP1	上游	5′-ACAAGAAAGACCAGAACCTGTTG-3′
	下游	5′-TGCATGAACCGCATAATCACAT-3′
GAPDH	上游	5′-CTGGGCTACACTGAGCACC-3′
	下游	5′-AAGTGGTCGTTGAGGGCAATG-3′

图1 SRGAP1在卵巢良性囊肿组织、卵巢癌组织和卵巢癌腹膜转移组织中的表达情况注：A SRGAP1在不同组织中的免疫组织化学染色,比例尺,左图为20×,右图为400× ;B 免疫组织化学的H-score统计图。a 与卵巢良性囊肿组织相比,P<0.05;b 与卵巢癌组织相比,P<0.05;C 蛋白质印迹验证SRGAP1在不同组织中的蛋白表达。实验重复3次;D 图C中SRGAP1相对蛋白表达灰度值直方图。a 与卵巢良性囊肿组织SRGAP1蛋白表达水平相比,P<0.05;b 与卵巢癌组织SRGAP1蛋白表达水平相比,P<0.05;E qRT-PCR验证SRGAP1在不同组织中的mRNA表达。实验重复3次。a 与卵巢良性囊肿组织SRGAP1 mRNA相对表达水平相比,P<0.05;b 与卵巢癌组织SRGAP1 mRNA相对表达水平相比,P<0.05。

表2 116例卵巢癌患者SRGAP1表达与临床病理参数的关系 [例（%）]

组别	n	年龄（岁）		FIGO分期		病理学分级		组织学分型		淋巴结转移
组别	n	<50 （n=43）	≥50 （n=73）	Ⅰ~Ⅱ （n=66）	Ⅲ~Ⅳ （n=50）	低级别（n=64）	高级别（n=52）	非上皮性（n=13）	上皮性（n=103）	阳性（n=38）	阴性（n=78）
SRGAP1低表达组	39	20（46.51）	19（26.03）	24（36.36）	15（30.00）	22（34.37）	17（32.69）	6（46.15）	33（32.04）	12（31.58）	27（34.62）
SRGAP1高表达组	77	23（53.49）	54（73.97）	42（63.64）	35（70.00）	42（65.63）	35（67.31）	7（53.85）	70（67.96）	26（68.42）	51（65.38）
χ²		0.662		0.948		8.867		6.432		0.353
P		0.444		0.208		0.005		0.021		0.733

图2 SRGAP1表达与卵巢癌患者预后的生存分析注：A 总生存期（OS）;B 无进展生存期（PFS）;C 进展后生存期（PSS）。

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