«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

29卷

期数:

2023年04期

页码:

366-371

栏目:

生物信息学专题

出版日期:

2023-07-10

文章信息/Info

Title:

Exploring the mechanism of malignant transformation of endometriosis based on bioinformatics analysis

文章编号:

1006-8147（2023）04-0366-06

作者:

吴桃¹; 呼学敏²; 杨玉芳²; 杜雪²

1.天津医科大学研究生院，天津300070;2.天津市人民医院/南开大学人民医院妇科，天津300121

Author(s):

WU Tao¹; HU Xue-min²; YANG Yu-fang²; DU Xue²

1.Graduate School，Tianjin Medical University，Tianjin 300070，China;2.Department of Gynecology，Tianjin Union Medical Center， Nankai University，Tianjin 300121，China

关键词:

子宫内膜异位症; 恶变; 卵巢透明细胞癌; 细胞焦亡; caspase-3

Keywords:

endometriosis; evil change; ovarian clear cell carcinoma; pyrosis; caspase-3

分类号:

R71

DOI:

-

文献标志码:

A

摘要:

目的：通过生物信息学分析探讨子宫内膜异位症（EMs）恶变为卵巢透明细胞癌（OCCC）的致病机制。方法：通过GEO数据库微阵列表达谱数据集GSE57545，分别将卵巢型EMs（OVE）、EMs相关OCCC与正常女性个体的免疫基因进行差异分析，并对差异表达基因进行GO富集和KEGG信号通路分析、构建差异表达基因的PPI网络并筛选Hub基因。结果：OVE与对照组间共筛选出43个差异表达基因，OCCC与对照组间共筛选出96个差异表达基因。相对于正常女性而言，KEGG信号通路富集显示：癌症通路是OVE与OCCC共有的信号通路。GO富集分析结果示：免疫系统过程、免疫反应、调节免疫系统进程等是OVE与OCCC共有的生物学过程；囊泡、质膜部分、细胞表面是OVE与OCCC的差异表达基因富集的共有细胞组分。CAPS3是OVE与OCCC的交集Hub基因。结论：免疫系统在EMs恶变的过程中起重要作用；CAPS3可能是EMs恶变为OCCC的关键靶点之一。

Abstract:

Objective：To investigate the pathogenesis of malignant transformation of endometriosis（ EMs） into ovarian clear cell carcinoma（ OCCC） by bioinformatics analysis. Methods：Through GEO database microarray expression profile dataset GSE57545，the immune genes of OVE，EMs related OCCC and normal female individuals were analyzed differentially. GO enrichment and KEGG signaling pathway analysis were performed for differentially expressed genes，PPI networks of differentially expressed genes were constructed and Hub genes were screened. Results：A total of 43 differentially expressed genes were screened between OVE and control group，and 96 differentially expressed genes were screened between OCCC and control group. Compared with normal female individuals，the enrichment of KEGG signaling pathway indicated that the cancer pathway was a common signaling pathway of OVE and OCCC. GO enrichment analysis results showed that the immune system process，immune response，regulation of immune system process were common biological processes of OVE and OCCC. The vesicles，plasma membrane and cell surface were the common components of OVE and OCCC enriched in DEGs. CAPS3 was the intersection Hub gene of OVE and OCCC. Conclusion：The immune system plays an important role in the malignant transformation of endometriosis；CAPS3 may be one of the key targets for the malignant transformation of EMs into OCCC.

参考文献/References:

[1] FRANCA PRC，LONTRA ACP，FERNANDES P D. Endometriosis：a disease with few direct treatment options[J]. Molecules，2022， 27（13）：4034.
[2] SZUKIEWICZ D，STANGRET A，RUIZ-RUIZ C，et al. Estrogen-and progesterone （ p4）-mediated epigenetic modifications of en－dometrial stromal cells （ enscs） and/or mesenchymal stem/stromal cells（ mscs） in the etiopathogenesis of endometriosis [J]. Stem Cell Rev Rep，2021，17（ 4）：1174-1193.
[3] YU S Y，LI X L. Pyroptosis and inflammasomes in obstetrical and gynecological diseases [J]. GynecolEndocrinol，2021，37（5）：385-391.
[4] SONG L，XING A，LI Q，et al. High-grade serous carcinoma result－ing from rectal endometriosis and complicated with ovarian cancer [J]. Front Oncol，2019，9：1252.
[5] BULUN S E，WAN Y，MATEI D. Epithelial mutations in endometrio－sis：link to ovarian cancer[J]. Endocrinology，2019，160（3）：626-638.
[6] 张国楠，向阳，王登凤，等.卵巢透明细胞癌临床诊治中国专家共识（ 2022年版）[J].中国实用妇科与产科杂志，2022，38（5）：515-523.
[7] YE Y，DAI Q，QI H. A novel defined pyroptosis-related gene signa－ture for predicting the prognosis of ovarian cancer[J]. Cell Death Discov，2021，7（ 1）：71.
[8] SZKLARCZYK D，FRANCESCHINI A，WYDER S，et al. STRING v10：protein-protein interaction networks，integrated over the tree of life[J]. Nucleic Acids Res，2015，43（ Database issue）：D447-D452.
[9] Cline M S，Smoot M，Cerami E，et al. Integration of biological net－works and gene expression data using cytoscape[J]. Nat Protoc，2007， 2（ 10）：2366-2382.
[10] LEENEN S，HERMENS M，DE VOS VAN STEENWIJK P J，et al. Immunologic factors involved in the malignant transformation of endometriosis to endometriosis-associated ovarian carcinoma [J]. Cancer Immunol Immunother. 2021，70（ 7）：1821-1829.
[11]黄怡，李瑞云，杨媛.细胞焦亡在妇科疾病中的研究进展[J].中国妇产科临床杂志，2022，23（ 4）：436-438.
[12] SCHECK S，PATERSON E S J，HENRY C E. A promising future for endometriosis diagnosis and therapy：extracellular vesicles-a sys－tematic review[J]. Reprod Biol Endocrinol，2022，20（ 1）：174
[13] LUCIDI A，BUCA D，RONSINI C，et al. Role of extracellular vesicles in epithelial ovarian cancer：a systematic review [J]. Int J Mol Sci， 2020，21（ 22）：8762.
[14] ESKANDARI E，EAVES C J. Paradoxical roles of caspase-3 in reg－ulating cell survival，proliferation，and tumorigenesis [J]. J Cell Biol， 2022，221（ 6）：e202201159.
[15] JIANG M，QI L，LI L，et al. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer[J]. Cell Death Discov，2020，6：112.
[16] WANG Y，GAO W，SHI X，et al. Chemotherapy drugs induce pyrop－tosis through caspase-3 cleavage of a gasdermin[J]. Nature，2017， 547（ 7661）：99-103.
[17] KIST M，VUCIC D. Cell death pathways：intricate connections and disease implications [J]. EMBO J，2021，40（ 5）：e106700.
[18] FRANK D，VINCE J E. Pyroptosis versus necroptosis：similarities， differences，and crosstalk[J]. Cell Death Differ，2019，26（1）：99-114.
[19] QI X，CHE X，LI Q，et al. Potential application of pyroptosis in kid－ney renal clear cell carcinoma immunotherapy and targeted therapy[J]. Front Pharmacol，2022，13：918647.
[20] KARKI R，KANNEGANTI T D. Diverging inflammasome signals in tumorigenesis and potential targeting[J]. Nat Rev Cancer，2019，19（4）：197-214.
[21] 廖文欣，李洋，申复进.细胞焦亡在妇科恶性肿瘤中的研究进展[J].中国计划生育和妇产科，2022，14（ 6）：41-45.
[22] LIANG J，ZHOU J，XU Y，et al. Osthole inhibits ovarian carcinoma cells through LC3-mediated autophagy and GSDME-dependent py－roptosis except for apoptosis[J]. Eur J Pharmacol，2020，874：172990.
[23] HANG Y，TAN L，CHEN Q，et al. E3 ubiquitin ligase TRIM24 defi－ciency promotes NLRP3/caspase-1/IL-1beta-mediated pyroptosis in endometriosis [J]. Cell Biol Int，2021，45（ 7）：1561-1570.
[24] YANG Y，LIU P Y，BAO W，et al. Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated py－roptotic pathway[J]. BMC Cancer，2020，20（ 1）：28.
[25] DU T，GAO J，LI P，et al. Pyroptosis，metabolism，and tumor immune microenvironment[J]. Clin Transl Med，2021，11（ 8）：e492.
[26] HUANG Y，LI R，YANG Y. Role of pyroptosis in gynecological on－cology and its therapeutic regulation[J]. Biomolecules，2022，12（ 7）：924.
[27] QIAO L，WU X，ZHANG J，et al. alpha-NETA induces pyroptosis of epithelial ovarian cancer cells through the GSDMD/caspase-4 path－way[J]. FASEB J，2019，33（ 11）：12760-12767.
[28] ZOU J，ZHENG Y，HUANG Y，et al. The versatile gasdermin family：their function and roles in diseases[J]. Front Immunol，2021，12：751533.
[29] RUAN J，WANG S，WANG J. Mechanism and regulation of pyropto－sis-mediated in cancer cell death[J]. Chem Biol Interact，2020，323：109052.

相似文献/References:

[1]刘颂平综述,华克勤审校.巨噬细胞在子宫内膜异位症发生发展中的作用研究现状[J].天津医科大学学报,2018,24(03):271.
[2]刘怡瑾,马平川,朱颖军.腹壁子宫内膜异位症的临床资料分析[J].天津医科大学学报,2018,24(04):336.
　LIU Yi-jin,MA Ping-chuan,ZHU Ying-jun.Clinical analysis of abdominal wall endometriosis[J].Journal of Tianjin Medical University,2018,24(04):336.
[3]耿莉莉,杜雪.子宫内膜息肉恶变的临床因素分析及宫腔镜下特征性差异[J].天津医科大学学报,2021,27(04):392.
　GENG Li-li,DU Xue.Clinical factors analysis of endometrial polyps malignancy and characteristic difference under hysteroscopy[J].Journal of Tianjin Medical University,2021,27(04):392.

备注/Memo

备注/Memo:

作者简介吴桃（1984-），女，硕士在读，研究方向：妇科内分泌；
通信作者：杜雪：E-mail：lanlandetommao@163.com。

常用功能

更新日期/Last Update: 2023-07-10