Yuan Mingwei, Chen Sijing, Liao Zelan, Wang Kana
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
Front Endocrinol (Lausanne). 2025 Mar 17;16:1450892. doi: 10.3389/fendo.2025.1450892. eCollection 2025.
Endometriosis-associated ovarian cancer (EAOC), an aggressive form of malignant ovarian neoplasm with origins in endometriosis (EM), has risen to prominence recently. Despite extensive investigation, the precise pathophysiology remains elusive.This article explores new autophagy-related DEG genes between EM and EAOC, and investigates CXCL12's expression and prognostic relevance across pan-cancer.
From Gene Expression Omnibus (GEO), we retrieved gene sequencing data to uncover DEGs. We carried out enrichment analysis, PPI network construction and explored CXCL12's multi-database expression and prognostic significance employing the analytical tools of ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter. Subsequently, assessing the relationship between CXCL12 expression and immune presence in cancer utilizing GEPIA and TIMER. Lastly, CXCL12, IL17, STAT3, and FOXP3 protein expressions were determined through immunohistochemistry analysis in EAOC, EM, and normal endometrial tissues.
Two DEGs were discovered and enrichment analysis indicated virus-cytokine/receptor interactions, chemokine signaling, and cytokine-cytokine receptor interplay as pivotal in EAOC. Notably, cancerous tissues exhibited reduced CXCL12 levels compared with non-malignant tissues across cancers. CXCL12, IL17, STAT3, Th17/Treg ratio, and FOXP3 expressions were also lower in EAOC than EM and normal tissues. Additionally, CXCL12 expression was related to stage, survival, immune subtype, and molecular classification across cancers.
In conclusion, our study implicates CXCL12 and altered Th17/Treg balance in progression from EM to EAOC. CXCL12 emerges as a predictive marker for cancer progression across various tumors and is associated with inflammatory response.
子宫内膜异位症相关卵巢癌（EAOC）是一种起源于子宫内膜异位症（EM）的侵袭性恶性卵巢肿瘤，近年来备受关注。尽管进行了广泛研究，但其确切病理生理学仍不清楚。本文探讨了EM和EAOC之间新的自噬相关差异表达基因（DEG），并研究了CXCL12在泛癌中的表达及预后相关性。
从基因表达综合数据库（GEO）中检索基因测序数据以发现DEG。我们进行了富集分析、蛋白质-蛋白质相互作用（PPI）网络构建，并使用ONCOMINE、PrognoScan、GEPIA和Kaplan-Meier Plotter等分析工具探索CXCL12的多数据库表达及预后意义。随后，利用GEPIA和TIMER评估CXCL12表达与癌症中免疫状态的关系。最后，通过免疫组织化学分析确定EAOC、EM和正常子宫内膜组织中CXCL12、白细胞介素17（IL17）、信号转导和转录激活因子3（STAT3）以及叉头盒P3（FOXP3）蛋白的表达。
发现了两个DEG，富集分析表明病毒-细胞因子/受体相互作用、趋化因子信号传导和细胞因子-细胞因子受体相互作用在EAOC中起关键作用。值得注意的是，与非恶性组织相比，癌组织中CXCL12水平在各种癌症中均降低。EAOC中CXCL12、IL17、STAT3、辅助性T细胞17（Th17）/调节性T细胞（Treg）比值和FOXP3的表达也低于EM和正常组织。此外，CXCL12表达与各种癌症的分期、生存率、免疫亚型和分子分类有关。
总之，我们的研究表明CXCL12以及Th17/Treg平衡改变参与了从EM到EAOC的进展过程。CXCL12成为各种肿瘤癌症进展的预测标志物，并与炎症反应相关。
