SPINT2的高表达促进卵巢癌的免疫浸润和肿瘤进展

IF 0.5 4区 医学 Q4 OBSTETRICS & GYNECOLOGY European journal of gynaecological oncology Pub Date : 2023-01-01 DOI:10.22514/ejgo.2023.086
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引用次数: 0

摘要

本研究旨在探讨丝氨酸肽酶抑制剂Kunitz 2型(SPINT2)在卵巢癌(OC)中的作用及机制。利用基因表达图谱(Gene expression Omnibus, GEO)和癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库分析SPINT2的表达。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)途径分析,确定SPINT2及其相关基因的丰富功能类别。利用Tumor immune Estimation Resource (TIMER) web server分析SPINT2与OC免疫浸润水平的相关性。采用细胞计数试剂盒-8 (CCK-8)和集落形成实验检测SPINT2对细胞增殖的影响。用transwell法检测其对细胞迁移和侵袭的影响。通过迁移实验检测SPINT2在M2巨噬细胞募集中的作用。利用M2巨噬细胞标志物和检测白细胞介素10 (IL-10)释放来评估SPINT2对M2巨噬细胞分化的作用。一项OC队列研究(GSE12470)显示SPINT2在OC中高表达。SPINT2高表达与较短的总生存期(OS)和较差的无复发生存期(RFS)相关。GO和KEGG分析表明,SPINT2相关基因在糖蛋白分解代谢、细胞粘附和T细胞分化中发挥作用。SPINT2在OC中巨噬细胞的浸润中也发挥了关键作用。shSPINT2降低卵巢癌细胞系SK-OV-3细胞的活力和集落形成能力。此外,shSPINT2还能抑制细胞的迁移和侵袭。shSPINT2转染的SK-OV-3细胞与巨噬细胞共培养可抑制M2巨噬细胞的迁移,抑制巨噬细胞从M0向M2极化。这些结果表明SPINT2参与肿瘤相关巨噬细胞(tam)的浸润。SPINT2在巨噬细胞的极化和迁移中也起着重要的作用。这些发现表明,SPINT2有潜力作为OC的生物标志物和潜在靶点进行探索。
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High expression of SPINT2 promotes immune infiltration and tumor progression in ovarian cancer
This study aimed to identify the function and mechanism of Serine Peptidase Inhibitor, Kunitz Type 2 (SPINT2) in ovarian cancer (OC). The expression of SPINT2 was analyzed using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify enriched functional categories of SPINT2 and its correlated genes. Correlation of SPINT2 with OC immune infiltration level was analyzed using the Tumor IMmune Estimation Resource (TIMER) web server. The effect of SPINT2 on cell proliferation was detected using cell counting kit-8 (CCK-8) and colony formation assay. Its effects on cell migration and invasion were examined using the transwell assay. Function of SPINT2 in M2 macrophage recruitment was detected using the migration assay. The role of SPINT2 on M2 macrophage differentiation was evaluated using M2 macrophage markers and by detection of interleukin 10 (IL-10) release. An OC cohort study (GSE12470) showed that SPINT2 was highly expressed in OC. The high SPINT2 expression was related to shorter overall survival (OS) and poor recurrence-free survival (RFS). GO and KEGG analysis indicated that SPINT2 associated genes played roles in glycoprotein catabolism, cell adhesion and T cell differentiation. SPINT2 also played a key role in infiltration of macrophages in OC. shSPINT2 reduced viability and colony formation ability of ovarian cancer cell line SK-OV-3 cells. Moreover, shSPINT2 also inhibited the cell migration and invasion. Co-culture of shSPINT2 transfected SK-OV-3 cells with macrophages inhibited the migration of M2 macrophages, and inhibited macrophages polarization from M0 to M2. These results suggested that SPINT2 is involved in infiltration of tumor-associated macrophages (TAMs). SPINT2 also plays an important role in the polarization and migration of macrophages. These findings suggested that SPINT2 has the potential to be explored as a biomarker for OC and a potential target.
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来源期刊
自引率
25.00%
发文量
58
审稿时长
1 months
期刊介绍: EJGO is dedicated to publishing editorial articles in the Distinguished Expert Series and original research papers, case reports, letters to the Editor, book reviews, and newsletters. The Journal was founded in 1980 the second gynaecologic oncology hyperspecialization Journal in the world. Its aim is the diffusion of scientific, clinical and practical progress, and knowledge in female neoplastic diseases in an interdisciplinary approach among gynaecologists, oncologists, radiotherapists, surgeons, chemotherapists, pathologists, epidemiologists, and so on.
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