# CXCL12 and eotaxin are independent prognostic serum biomarkers in gastric cancer

**Authors:** Jefim Brodkin, Tuomas Kaprio, Harri Mustonen, Alli Leppä, Arto Kokkola, Marko Salmi, Sirpa Jalkanen, Caj Haglund, Camilla Böckelman

PMC · DOI: 10.1038/s41598-026-46511-z · Scientific Reports · 2026-03-29

## TL;DR

This study identifies CXCL12 and eotaxin as independent blood-based biomarkers that predict survival in gastric cancer patients.

## Contribution

CXCL12 and eotaxin are shown to be novel independent prognostic serum biomarkers for gastric cancer.

## Key findings

- CXCL12 and eotaxin were found to be independent prognostic markers for disease-specific survival in gastric cancer patients.
- Three biomarkers (CXCL12, stem cell factor, and eotaxin) were significantly associated with survival in univariate analysis.
- The study analyzed 48 biomarkers using a cytokine assay to identify prognostic serum markers in gastric cancer.

## Abstract

Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer-related death worldwide. Its poor prognosis primarily results from a late diagnosis and the lack of effective treatments for advanced disease. Thus, we aimed to identify new prognostic serum biomarkers to aid clinical decision-making. Our patient cohort consisted of 240 individuals who underwent surgery for histologically verified gastric adenocarcinoma in the Department of Surgery at Helsinki University Hospital between 2000 and 2009. To determine the serum protein concentrations of cytokines and growth factors, we utilized Bio-Rad’s premixed Bio-Plex Pro Human Cytokine 27- and 21-plex assay kits. Among the 48 biomarkers we analyzed, three emerged as statistically significant prognostic markers for disease-specific survival using the Cox proportional hazards univariate analysis: C-X-C motif chemokine ligand 12 (CXCL12) (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.23–0.63, p < 0.001), stem cell factor (HR 0.38, 95% CI 0.19–0.77, p = 0.007), and eotaxin (HR 0.57, 95% CI 0.37–0.89, p = 0.013). Our multivariate survival analysis revealed that, among the 48 biomarkers analyzed, CXCL12 and eotaxin served as independent prognostic markers among gastric cancer patients. The prognostic effect of inflammatory serum biomarkers in gastric cancer may provide new insights into the immunological microenvironment of disease.

The online version contains supplementary material available at 10.1038/s41598-026-46511-z.

## Linked entities

- **Proteins:** CXCL12 (C-X-C motif chemokine ligand 12), Ccl11 (C-C motif chemokine ligand 11)
- **Diseases:** gastric cancer (MONDO:0001056), gastric adenocarcinoma (MONDO:0005036)

## Full-text entities

- **Genes:** ACKR3 (atypical chemokine receptor 3) [NCBI Gene 57007] {aka CMKOR1, CXC-R7, CXCR-7, CXCR7, GPR159, RDC-1}, RBBP4 (RB binding protein 4, chromatin remodeling factor) [NCBI Gene 5928] {aka NURF55, RBAP48, lin-53}, OSM (oncostatin M) [NCBI Gene 5008], CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, MSH2 (mutS homolog 2) [NCBI Gene 4436] {aka COCA1, FCC1, HNPCC, HNPCC1, LCFS2, LYNCH1}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, IL10RB (interleukin 10 receptor subunit beta) [NCBI Gene 3588] {aka CDW210B, CRF2-4, CRFB4, D21S58, D21S66, IBD25}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, PMS2 (PMS1 homolog 2, mismatch repair system component) [NCBI Gene 5395] {aka HNPCC4, LYNCH4, MLH4, MMRCS4, PMS-2, PMSL2}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, CCR3 (C-C motif chemokine receptor 3) [NCBI Gene 1232] {aka C C CKR3, CC-CKR-3, CD193, CKR 3, CKR3, CMKBR3}, MLH1 (mutL homolog 1) [NCBI Gene 4292] {aka COCA2, FCC2, HNPCC, HNPCC2, LYNCH2, MLH-1}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, IL3 (interleukin 3) [NCBI Gene 3562] {aka IL-3, MCGF, MULTI-CSF}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, ADA (adenosine deaminase) [NCBI Gene 100] {aka ADA1}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, KITLG (KIT ligand) [NCBI Gene 4254] {aka DCUA, DFNA69, FPH2, FPHH, KL-1, Kitl}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, MSH6 (mutS homolog 6) [NCBI Gene 2956] {aka GTBP, GTMBP, HNPCC5, HSAP, LYNCH5, MMRCS3}, TNFRSF8 (TNF receptor superfamily member 8) [NCBI Gene 943] {aka CD30, D1S166E, Ki-1}, IL20 (interleukin 20) [NCBI Gene 50604] {aka IL-20, IL10D, ZCYTO10}
- **Diseases:** adenocarcinoma (MESH:D000230), infection (MESH:D007239), node (MESH:D012804), microsatellite instability (MESH:D053842), GIST (MESH:D046152), lymph node (MESH:D000072717), oral squamous cell cancer (MESH:D018307), intestinal metaplasia (MESH:D007410), metastases (MESH:D009362), gastrointestinal malignancies (MESH:D005770), disease (MESH:D004194), Cancer (MESH:D009369), death (MESH:D003643), TNM (MESH:D008207), breast cancer (MESH:D001943), GS (MESH:D060050), dysplasia (MESH:D015792), GC (MESH:D013274), H. pylori (MESH:D016481), ovarian and colorectal cancer (MESH:D010051), CIN (MESH:D043171), colorectal cancer (MESH:D015179), atrophic gastritis (MESH:D005757), EBV (MESH:D020031), Chronic inflammation (MESH:D007249), chronic gastritis (MESH:D005756), allergic reactions (MESH:D004342), esophagogastric and pancreatic cancer (MESH:D010190)
- **Chemicals:** EOX (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376]

## Full text

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## Figures

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## References

3 references — full list in the complete paper: https://tomesphere.com/paper/PMC13039986/full.md

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Source: https://tomesphere.com/paper/PMC13039986