FOLR1与MSLN蛋白在上皮性卵巢癌组织中的表达及临床意义

梁振; 董郊; 李凤杰; 杨泽宇; 王延洲; 梁志清

doi:10.16016/j.1000-5404.201908081

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FOLR1与MSLN蛋白在上皮性卵巢癌组织中的表达及临床意义

基础医学 | 更新时间：2026-01-09

- FOLR1与MSLN蛋白在上皮性卵巢癌组织中的表达及临床意义
- Expression of folate receptor 1 and mesothelin proteins in epithelial ovarian cancer and their clinical significance
- 第三军医大学学报 2020年42卷第2期页码：133-140
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)第一附属医院:妇产科
  2.400038 重庆，陆军军医大学(第三军医大学)第一附属医院:全军临床病理学研究所，西南癌症中心
- 作者简介：
  
  [梁志清，E-mail:zhi.lzliang@gmail.com LIANG Zhiqing, E-mail:zhi.lzliang@gmail.com
- 基金信息：
  
  陆军军医大学第一附属医院重大领域技术创新计划项目(SWH2016ZDCX1013)
- DOI：10.16016/j.1000-5404.201908081
  中图分类号： R341;R730.23;R737.31
- 收稿：2019-08-12，
  
  修回：2019-10-30，
  
  纸质出版：2020-01-30
- 稿件说明：
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梁振, 董郊, 李凤杰, 等. FOLR1与MSLN蛋白在上皮性卵巢癌组织中的表达及临床意义[J]. 第三军医大学学报, 2020,42(2):133-140.

Zhen LIANG, Jiao DONG, Fengjie LI, et al. Expression of folate receptor 1 and mesothelin proteins in epithelial ovarian cancer and their clinical significance[J]. Journal of Third Military Medical University, 2020, 42(2): 133-140.
梁振, 董郊, 李凤杰, 等. FOLR1与MSLN蛋白在上皮性卵巢癌组织中的表达及临床意义[J]. 第三军医大学学报, 2020,42(2):133-140. DOI： 10.16016/j.1000-5404.201908081.

Zhen LIANG, Jiao DONG, Fengjie LI, et al. Expression of folate receptor 1 and mesothelin proteins in epithelial ovarian cancer and their clinical significance[J]. Journal of Third Military Medical University, 2020, 42(2): 133-140. DOI： 10.16016/j.1000-5404.201908081.

摘要

目的

研究FOLR1(folate receptor 1)和MSLN(mesothelin)在上皮性卵巢癌(epithelial ovarian cancer

EOC)中的表达和临床意义。

方法

获取GEO、TCGA数据库(Ovarian Cancer TCGA

Provisional; GSE6008; GSE66957; GSE49997)EOC临床样本信息和转录组测序表达矩阵；分析不同组织的表达情况及其与肿瘤的分期、预后的关系；收集本院2018-2019年EOC(105例)、卵巢交界性肿瘤(11例)、正常卵巢组织(30例)；免疫组化法检测FOLR1和MSLN表达情况与卵巢癌患者临床病理特征间的关系。

结果

GEO、TCGA数据库分析显示:EOC组织中FOLR1和MSLN mRNA表达量明显高于正常组织(

0.05)，Ⅲ~Ⅳ期病人表达量明显高于Ⅰ~Ⅱ期卵巢癌(

0.05)，生存分析显示FOLR1高表达的患者预后好(总体生存期:

0.05；无病生存期:

0.05)，MSLN高表达患者预后差(总体生存期:

0.05；无病生存期:

0.05)。146例卵巢组织免疫组化分析显示:FOLR1和MSLN蛋白在正常卵巢组织中低表达，交界性卵巢肿瘤组织中表达上升，在EOC组织中表达明显升高，阳性表达率分别为80.95%、53.33%。不同组织类型的表达具有统计学差异(

0.001)；Ⅲ~Ⅳ期病人阳性率明显高于Ⅰ~Ⅱ期(

0.05)；淋巴结转移的患者MSLN的阳性率明显升高(

0.05)。TCGA数据库亚组生存分析显示在mRNA水平MSLN低表达和FOLR1高表达的患者(M

)预后最好，MSLN高表达和FOLR1低表达的患者(M

)预后最差(中位生存期70.57

25.85个月，

0.000 1)。相比于M

组，M

组早期(

50个月)预后较好，而超过50个月则生存率明显下降，但此种差异无统计学意义。

结论

FOLR1高表达的EOC患者预后好，MSLN高表达的患者预后差。两种蛋白可能共同参与了EOC的进程，联合检测FOLR1和MSLN两种蛋白的表达，有助于EOC的预后判断。

Abstract

Objective

To investigate the expression of folate receptor 1(FOLR1) and mesothelin (MSLN) in epithelial ovarian cancer(EOC) and explore their clinical significance.

Methods

The data of clinical samples and transcriptome sequencing expression matrix of EOC were obtained from TCGA and GEO database(Ovarian Cancer TCGA

Provisional; GSE6008; GSE66957; GSE49997) to analyze the expressions of FOLR1 and MSLN in different tissues and their association with tumor staging and the prognosis of EOC. We also collected paraffin-embedded tissue samples of EOC(105 cases)

ovarian borderline tumor(11 cases)

and normal ovarian tissue(30 cases) from patients undergoing surgeries in our hospital between 2018 and 2019. The expression levels of FOLR1 and MSLN were detected by immunohistochemistry and their correlation with the clinicopathological characteristics of the patients was analyzed.

Results

Analysis of TCGA and GEO databases showed that the mRNA levels of FOLR1 and MSLN were significantly higher in EOC tissues than in normal ovarian tissues(

0.05)

and was also higher in stage Ⅲ~Ⅳ than in stage Ⅰ~Ⅱ EOC(

0.05). Survival analysis showed that the patients with a high expression of FOLR1 had significantly longer overall survival(

0.05) and disease-free survival(

0.05)

while the patients with a high expression of MSLN had significantly shortened overall survival(

0.05) and disease-free survival(

0.05). Immunohistochemical analysis showed that FOLR1 and MSLN proteins were lowly expressed in normal ovarian tissues

and their expressions increased moderately in borderline ovarian tumor and significantly in EOC tissues. The positive expression rates of FOLR1 and MSLN in EOC were 80.95% and 53.33%

respectively. The levels were of FOLR1 and MSLN differed significantly in different tissue types(

0.001)

and their positive rates were significantly higher in stage Ⅲ~Ⅳ than in stage Ⅰ~Ⅱ EOC(

0.05). The positive rate of MSLN was significantly increased in patients with lymph node metastasis(

0.05). Subgroup survival analysis of TCGA database showed that patients with a low MSLN expression and a high FOLR1 expression(M

) at the mRNA level had the best prognosis

while those with a high MSLN expression and a low FOLR1 expression(M

) had the worst prognosis(median survival time 70.57

25.85 months

0.000 1); compared with the M

patients

the M

patients in the early stage(

50 months) had a better prognosis

while beyond 50 months

the survival rate of the patients decreased

but the difference was not statistically

significant.

Conclusion

In patients with EOC

a high expression of FOLR1 indicates a more favorable prognosis while a high expression of MSLN is associated with a poor prognosis. These 2 proteins may participate in the process of EOC

and their combined detection may help in prognostic evaluation of EOC.

关键词

Keywords

references

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