干扰素诱导基因IFIT1与卵巢癌免疫浸润及预后的相关性

王瑞伟; 李凤杰; 梁小龙; 周鑫; 刘丽萍; 李秋蓉; 何明敏; 李宇迪

doi:10.16016/j.2097-0927.202305038

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干扰素诱导基因IFIT1与卵巢癌免疫浸润及预后的相关性

基础医学 | 更新时间：2026-01-09

- 干扰素诱导基因IFIT1与卵巢癌免疫浸润及预后的相关性
- Correlation of interferon-induced gene IFIT1 with immune infiltration and prognosis in ovarian cancer
- 陆军军医大学学报 2024年46卷第10期页码：1132-1141
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院妇产科
- 作者简介：
  
  [李宇迪，E-mail：lydyzj1971@sina.com LI Yudi, E-mail: lydyzj1971@sina.com
- 基金信息：
  
  重庆市卫生适宜技术推广项目(2021jstg010)
- DOI：10.16016/j.2097-0927.202305038
  中图分类号： R394.3;R73-37;R737.31
- 收稿：2023-05-15，
  
  修回：2023-11-24，
  
  纸质出版：2024-05-30
- 稿件说明：
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王瑞伟, 李凤杰, 梁小龙, 等. 干扰素诱导基因IFIT1与卵巢癌免疫浸润及预后的相关性[J]. 陆军军医大学学报, 2024,46(10):1132-1141.

Ruiwei WANG, Fengjie LI, Xiaolong LIANG, et al. Correlation of interferon-induced gene IFIT1 with immune infiltration and prognosis in ovarian cancer[J]. Journal of Army Medical University, 2024, 46(10): 1132-1141.
王瑞伟, 李凤杰, 梁小龙, 等. 干扰素诱导基因IFIT1与卵巢癌免疫浸润及预后的相关性[J]. 陆军军医大学学报, 2024,46(10):1132-1141. DOI： 10.16016/j.2097-0927.202305038.

Ruiwei WANG, Fengjie LI, Xiaolong LIANG, et al. Correlation of interferon-induced gene IFIT1 with immune infiltration and prognosis in ovarian cancer[J]. Journal of Army Medical University, 2024, 46(10): 1132-1141. DOI： 10.16016/j.2097-0927.202305038.

摘要

目的

探讨干扰素诱导基因IFIT1与卵巢癌免疫浸润及预后的相关性。

方法

通过GEO数据库筛选肿瘤免疫相关基因，Kaplan-Meier与Prognoscan预后数据库筛选与卵巢癌预后显著相关的差异基因。GEPIA、Human Protein Atlas与Timer数据库分析IFIT1在卵巢癌组织与正常组织中的表达差异。UALCAN数据库分析IFIT1在不同分级和分期的卵巢癌组织中的表达情况。David数据库对String和Genemania数据库筛选的相互作用基因与蛋白进行GO富集分析。Timer和Tisidb数据库相互验证IFIT1与免疫细胞的相关性。IFIT1干扰质粒成功构建后，利用IFIT1干扰稳转株构建裸鼠移植瘤模型，观察IFIT1敲降后肿瘤生长情况，免疫组化检测中性粒细胞浸润。

结果

GEO数据库、Kaplan-Meier与Prognoscan预后数据库筛选出IFIT1是与卵巢癌预后显著负相关的肿瘤免疫基因。GEPIA、Human Protein Atlas、Timer数据库以及UALCAN数据库表明IFIT1在卵巢癌组织中表达显著高于正常卵巢组织(

＜0.05)，但与肿瘤的分期、分级并不存在显著相关性。String、Genemania、David数据库分析发现IFIT1的互作基因与蛋白富集于2’-5’寡聚腺苷酸合成酶的活化、病毒防御、先天性免疫等过程。Timer数据库表明IFIT1与卵巢癌中CD8

T细胞、B细胞、树突状细胞、中性粒细胞和巨噬细胞浸润呈正相关，其中与中性粒细胞相关性最为明显(

＜0.001)。Tisidb与GSCA均验证了IFIT1与卵巢癌组织的中性粒细胞浸润呈高度正相关(

＜0.05)。RT-qPCR和Western blot证明卵巢癌细胞中IFIT1被成功敲降后，IFIT1干扰细胞的移植瘤生长显著减缓(

＜0.05)，肿瘤中性粒细胞浸润减少。

结论

IFIT1可能促进中性粒细胞浸润影响卵巢癌的恶性进程。

Abstract

Objective

To analyze the correlation of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) with immune infiltration and prognosis of ovarian cancer (OC).

Methods

GEO database was employed to select the tumor immune related genes

and Kaplan-Meier and Prognoscan databases were used to identify the genes significantly associated with OC prognosis. The differential expression of IFIT1 between OC tissue and normal tissue were confirmed with GEPIA

Human Protein Atlas

and Timer databases. The expression level of IFIT1 in OC tissues with different grades and stages were analyzed in the UALCAN database. In addition

based on David database

GO enrichment analysis was used to analyze the interacting genes and proteins of IFIT1 in the String and Genemania databases. Timer and Tisidb databases verified the correlation between IFIT1 and immune cells mutually. Finally

after IFIT1 knockdown xenograft model was constructed based on lentiviral vector of IFIT1 shRNA

the tumor growth was observed in the transplanted nude mice

and infiltration of neutrophils was observed with immunohistochemical assay.

Results

FIT1

a tumor immune gene

selected from the GEO database

Kaplan-Meier and Prognoscan databases

was negatively correlated with the OC prognosis. GEPIA

Human Protein Atlas

Timer database

and UALCAN database indicated that the expression level of IFIT1 was significantly higher in the OC tissues than the normal ovarian tissues

and had no obvious correlation with tumor stage and grade. Analysis in String

Genemania

and David database found the interaction genes and proteins of IFIT1 were enriched in activation of 2'-5' oligonucleotide synthase

virus defense

and innate immunity

and other processes. The Timer database presented that IFIT1 was positively correlated with the infiltration of CD8

T cells

B cells

dendritic cells

neutrophils

and macrophage in OC

with neutrophils having the most significant correlation. Tisidb and GSCA also confirmed the positive correlation between IFIT1 and neutrophil infiltration in OC (

0.05). RT-qPCR and Western blotting confirmed that IFIT1 knockdown resulted in suppressed tumor growth in OC cells xenograft nude mice (

0.05) and reduced neutrophil infiltration in the xenograft tissues.

Conclusion

IFIT1 may influence the malignant progression of OC by promoting neutrophil infiltration.

关键词

Keywords

references

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