# The expression of autophagy-related gene CXCL12 in endometriosis associated ovarian cancer and pan-cancer analysis

**Authors:** Mingwei Yuan, Sijing Chen, Zelan Liao, Kana Wang

PMC · DOI: 10.3389/fendo.2025.1450892 · Frontiers in Endocrinology · 2025-03-17

## TL;DR

This study investigates the role of the autophagy-related gene CXCL12 in endometriosis-associated ovarian cancer and its relevance across various cancers.

## Contribution

The study identifies CXCL12 as a novel predictive marker for cancer progression and highlights its association with immune response in endometriosis and cancer.

## Key findings

- CXCL12 levels are reduced in cancerous tissues compared to non-malignant tissues across cancers.
- CXCL12 expression correlates with cancer stage, survival, immune subtype, and molecular classification.
- CXCL12 and altered Th17/Treg balance are implicated in the progression from endometriosis to endometriosis-associated ovarian cancer.

## Abstract

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.

## Linked entities

- **Genes:** CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387], IL17A (interleukin 17A) [NCBI Gene 3605], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774], FOXP3 (forkhead box P3) [NCBI Gene 50943]
- **Proteins:** CXCL12 (C-X-C motif chemokine ligand 12), IL17A (interleukin 17A), STAT3 (signal transducer and activator of transcription 3), FOXP3 (forkhead box P3)
- **Diseases:** endometriosis (MONDO:0005133), ovarian cancer (MONDO:0005140)

## Full-text entities

- **Genes:** FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}
- **Diseases:** cancer (MESH:D009369), inflammatory (MESH:D007249), EM (MESH:D004715), EAOC (MESH:D010051)

## Full text

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## Figures

16 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11955448/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC11955448/full.md

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Source: https://tomesphere.com/paper/PMC11955448