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卵巢癌中的PHD指状蛋白20样蛋白1（PHF20L1）：从其在组织中的过表达到腹水微环境对其的上调作用

PHD finger protein 20-like protein 1 (PHF20L1) in ovarian cancer: from its overexpression in tissue to its upregulation by the ascites microenvironment.

作者信息

Alberto-Aguilar Dulce Rosario, Hernández-Ramírez Verónica Ivonne, Osorio-Trujillo Juan Carlos, Gallardo-Rincón Dolores, Toledo-Leyva Alfredo, Talamás-Rohana Patricia

机构信息

Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, 07360, Mexico City, Mexico.

Instituto Nacional de Cancerología, Av. San Fernando No. 22, Col. Sección XVI, Delegación Tlalpan, 07360, Mexico City, Mexico.

出版信息

Cancer Cell Int. 2022 Jan 6;22(1):6. doi: 10.1186/s12935-021-02425-6.

DOI:10.1186/s12935-021-02425-6
PMID:34991589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8740351/
Abstract

BACKGROUND

Ovarian cancer is the most aggressive gynecological malignancy. Transcriptional regulators impact the tumor phenotype and, consequently, clinical progression and response to therapy. PHD finger protein 20-like protein 1 (PHF20L1) is a transcriptional regulator with several isoforms, and studies on its role in ovarian cancer are limited. We previously reported that PHF20L1 is expressed as a fucosylated protein in SKOV-3 cells stimulated with ascites from patients with ovarian cancer.

METHODS

We decided to analyze the expression of PHF20L1 in ovarian cancer tissues, determine whether a correlation exists between PHF20L1 expression and patient clinical data, and analyze whether ascites can modulate the different isoforms of this protein. Ovarian cancer biopsies from 29 different patients were analyzed by immunohistochemistry, and the expression of the isoforms in ovarian cancer cells with or without exposure to the tumor microenvironment, i.e., the ascitic fluid, was determined by western blotting assays.

RESULTS

Immunohistochemical results suggest that PHF20L1 exhibits increased expression in sections of tumor tissues from patients with ovarian cancer and that higher PHF20L1 expression correlates with shorter progression-free survival and shorter overall survival. Furthermore, western blotting assays determined that protein isoforms are differentially regulated in SKOV-3 cells in response to stimulation with ascites from patients with epithelial ovarian cancer.

CONCLUSION

The results suggest that PHF20L1 could play a relevant role in ovarian cancer given that higher PHF20L1 protein expression is associated with lower overall patient survival.

摘要

背景

卵巢癌是最具侵袭性的妇科恶性肿瘤。转录调节因子影响肿瘤表型，进而影响临床进展和对治疗的反应。PHD指蛋白20样蛋白1（PHF20L1）是一种具有多种异构体的转录调节因子，关于其在卵巢癌中作用的研究有限。我们之前报道过，在受到卵巢癌患者腹水刺激的SKOV-3细胞中，PHF20L1表达为一种岩藻糖基化蛋白。

方法

我们决定分析PHF20L1在卵巢癌组织中的表达，确定PHF20L1表达与患者临床数据之间是否存在相关性，并分析腹水是否能调节该蛋白的不同异构体。通过免疫组织化学分析了来自29名不同患者的卵巢癌活检样本，并通过蛋白质印迹分析确定了在有或无肿瘤微环境（即腹水）暴露情况下，卵巢癌细胞中异构体的表达情况。

结果

免疫组织化学结果表明，PHF20L1在卵巢癌患者肿瘤组织切片中的表达增加，且较高的PHF20L1表达与较短的无进展生存期和较短的总生存期相关。此外，蛋白质印迹分析确定，在SKOV-3细胞中，蛋白质异构体在受到上皮性卵巢癌患者腹水刺激后受到不同调节。

结论

结果表明，鉴于较高的PHF20L1蛋白表达与患者较低的总生存期相关，PHF20L1可能在卵巢癌中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/e819d2fc3286/12935_2021_2425_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/85a2f51f9c7c/12935_2021_2425_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/f2ba0518bea6/12935_2021_2425_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/7066a1ea80e0/12935_2021_2425_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/6c67e9403983/12935_2021_2425_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/e819d2fc3286/12935_2021_2425_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/85a2f51f9c7c/12935_2021_2425_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/f2ba0518bea6/12935_2021_2425_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/7066a1ea80e0/12935_2021_2425_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/6c67e9403983/12935_2021_2425_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/028c/8740351/e819d2fc3286/12935_2021_2425_Fig5_HTML.jpg

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