# Olink proteomics identifies FGF-19 as a treatment-responsive inflammatory biomarker associated with acupuncture intervention in young females with mild depression

**Authors:** Zhongxian Li, Zitong Jiao, Min Peng, Pan Zhang, Haiyan Xu, Ruiming Chen, Qiaoyu Ji, Jingjing Li, Lihua Chen, Beibei Zhao, Wenbin Fu, Peng Zhou

PMC · DOI: 10.3389/fpsyt.2026.1743771 · Frontiers in Psychiatry · 2026-02-19

## TL;DR

This study finds that FGF-19 is a treatment-responsive inflammatory biomarker linked to acupuncture in young women with mild depression.

## Contribution

FGF-19 is identified as a novel, treatment-responsive inflammatory biomarker for mild depression in young females following acupuncture.

## Key findings

- FGF-19 was significantly downregulated in mild depression and upregulated after acupuncture.
- FGF-19 levels were inversely correlated with depression scores and validated in an expanded cohort.
- Acupuncture modulated inflammatory proteins, with FGF-19 showing a bidirectional expression profile.

## Abstract

Mild depression in women is a distinct disorder with unclear immune mechanisms. This study aims to identify peripheral inflammatory biomarkers and to explore acupuncture’s immunomodulatory effects via Olink proteomics. Thirty female participants (18–45 years) were assigned to healthy controls (HC), mild depression (MD), and acupuncture treatment (ACU). Plasma samples were analyzed using the Olink® Target 96 Inflammation panel for differentially expressed proteins (DEPs) (Approval No. KY-2023-005-02), then analyzed for enrichment using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Correlations between DEPs and Hamilton Depression Rating Scale-17 items (HAMD-17) and Self-Rating Depression Scale (SDS) scores were assessed. Enzyme-linked immunosorbent assay (ELISA) was conducted on an expanded cohort (n=40/group) to validate key findings. Compared with HC, 15 proteins were significantly downregulated in MD (no proteins were upregulated), including FGF-19, SIRT2, and AXIN1. After acupuncture, six proteins were further downregulated, and three (FGF-19, FGF-5, IL-2) were significantly upregulated. ELISA validation confirmed that FGF-19, the sole protein significantly altered, was inversely correlated with depression scores and exhibited decreased expression in MD that was reversed by acupuncture. FGF-19’s bidirectional expression profile positions a promising inflammation-related biomarker and a potential treatment-responsive marker for mild depression in young females, also an indicator of acupuncture efficacy. Clinical Trial Registration Chinese Clinical Trial Registry, identifier ChiCTR2300068054.

https://www.chictr.org.cn/showprojEN.html?proj=189355, identifier ChiCTR2300068054.

Flowchart diagram outlining a study workflow for sample collection in females aged eighteen to forty-five, comparing healthy controls, mild depression cases, and an acupuncture group through bioinformatics analysis, FGF-19 identification, and ELISA validation as a potential inflammatory biomarker.

## Linked entities

- **Proteins:** FGF19 (fibroblast growth factor 19), SIRT2 (sirtuin 2), AXIN1 (axin 1), FGF5 (fibroblast growth factor 5), IL2 (interleukin 2)

## Full-text entities

- **Genes:** IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, LAP (Laryngeal adductor paralysis) [NCBI Gene 7939], IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CD5 (CD5 molecule) [NCBI Gene 921] {aka LEU1, T1}, NRTN (neurturin) [NCBI Gene 4902] {aka NTN}, FGF5 (fibroblast growth factor 5) [NCBI Gene 2250] {aka HBGF-5, Smag-82, TCMGLY}, ADA (adenosine deaminase) [NCBI Gene 100] {aka ADA1}, STAMBP (STAM binding protein) [NCBI Gene 10617] {aka AMSH, MICCAP}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, CCL28 (C-C motif chemokine ligand 28) [NCBI Gene 56477] {aka CCK1, MEC, SCYA28}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, SIRT2 (sirtuin 2) [NCBI Gene 22933] {aka SIR2, SIR2L, SIR2L2}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, AXIN1 (axin 1) [NCBI Gene 8312] {aka AXIN, CMDOH, PPP1R49}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, TNFSF12 (TNF superfamily member 12) [NCBI Gene 8742] {aka APO3L, DR3LG, TNF12, TNLG4A, TWEAK}, DNER (delta/notch like EGF repeat containing) [NCBI Gene 92737] {aka UNQ26, bet}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, FGF19 (fibroblast growth factor 19) [NCBI Gene 9965], SLAMF1 (signaling lymphocytic activation molecule family member 1) [NCBI Gene 6504] {aka CD150, CDw150, IPO3, SLAM}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, EIF4EBP1 (eukaryotic translation initiation factor 4E binding protein 1) [NCBI Gene 1978] {aka 4E-BP1, 4EBP1, BP-1, PHAS-I}, CCL13 (C-C motif chemokine ligand 13) [NCBI Gene 6357] {aka CKb10, MCP-4, NCC-1, NCC1, SCYA13, SCYL1}, CD244 (CD244 molecule) [NCBI Gene 51744] {aka 2B4, NAIL, NKR2B4, Nmrk, SLAMF4}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}
- **Diseases:** Depression (MESH:D003866), bipolar disorder (MESH:D001714), immune dysregulation (OMIM:614878), infectious diseases (MESH:D003141), ACU (MESH:D016609), COVID-19 (MESH:D000086382), Inflammation (MESH:D007249), infectious, cardiovascular, or respiratory diseases (MESH:D012140), HC (MESH:D000067329), alcohol dependence (MESH:D000437), substance abuse (MESH:D019966), psychiatric (MESH:D001523), cancer (MESH:D009369), schizophrenia (MESH:D012559), immunological or inflammatory disorders (MESH:C565684)
- **Chemicals:** TUDCA (MESH:C031655), UDCA (MESH:D014580), DCA (-), bile acid (MESH:D001647), CDCA (MESH:D002635), deoxycholic acid (MESH:D003840), EDTA (MESH:D004492)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** Val66Met

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960610/full.md

## References

25 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960610/full.md

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Source: https://tomesphere.com/paper/PMC12960610