# Bioinformatics-based analysis of the relationship between STC1 expression and immune infiltration in gastric cancer

**Authors:** Weijun Ma, Xiaoli Ma, Yaoqi Li

PMC · DOI: 10.3389/fgene.2025.1499121 · Frontiers in Genetics · 2025-07-16

## TL;DR

This study explores how STC1 expression in gastric cancer relates to immune cell infiltration and patient outcomes, suggesting it could be a target for immunotherapy.

## Contribution

The study identifies STC1 as a novel biomarker linked to immune infiltration and T-cell exhaustion in gastric cancer.

## Key findings

- STC1 expression is significantly higher in gastric cancer tissues and predicts poor survival.
- STC1 is associated with T-cell exhaustion and immune infiltration in the tumor microenvironment.
- Single-cell RNA sequencing confirms STC1 co-expression with T-cell exhaustion markers.

## Abstract

The study assessed the expression of STC1, and its potential as an immunotherapy target in gastric cancer (GC).

RNAseq data from the TCGA_STAD project and TCGA-GTEx project of UCSC XENA website and microarray data from GEO (GSE66229) were downloaded. Differential STC1 mRNA expression between GC and non-carcinoma tissues was examined. Its relation to clinicopathological characteristics and prognosis was evaluated using univariate and multivariate Cox regression. Tumor infiltrating immune cells (TIICs) in the tumor microenvironment (TME) were assessed by ssGSEA, and T-cell exhaustion by TIMER. Single-cell RNA sequencing (scRNA-seq) analysis was performed to validate the correlation between STC1 expression and T-cell exhaustion markers. Gene Set Enrichment Analysis (GSEA) was also conducted to explore potential functions of STC1 in GC.

STC1 expression was significantly higher in GC tissues and independently predicted poor overall survival. STC1 expression was related to patient T-stage, location, and overall survival events. Immune infiltration analysis showed significant associations between STC1 and multiple immune cells in TME, with strong links to T-cell exhaustion. scRNA-seq analysis confirmed the co-expression of STC1 with T-cell exhaustion markers in specific cell clusters. GSEA identified several signaling pathways, such as “SIGNALING_BY_INTERLEUKINS” and “JAK_STAT_SIGNALING_PATHWAY,” linked to STC1 expression in GC.

STC1 is a promising target for immunotherapy in GC, as its expression is correlated with patient prognosis, immune infiltration, and T-cell exhaustion.

## Linked entities

- **Genes:** STC1 (stanniocalcin 1) [NCBI Gene 6781]
- **Diseases:** gastric cancer (MONDO:0001056), GC (MONDO:0001056)

## Full-text entities

- **Genes:** PDCD1LG2 (programmed cell death 1 ligand 2) [NCBI Gene 80380] {aka B7DC, Btdc, CD273, PD-L2, PDCD1L2, PDL2}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868] {aka CD366, HAVcr-2, KIM-3, SPTCL, TIM3, TIMD-3}, CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}, STC1 (stanniocalcin 1) [NCBI Gene 6781] {aka STC}
- **Diseases:** ovarian cancer (MESH:D010051), hypoxic (MESH:D002534), GC (MESH:D013274), colon cancer (MESH:D015179), lung cancer (MESH:D008175), paraneoplastic (MESH:D010257), breast cancer (MESH:D001943), Helicobacter pylori infection (MESH:D016481), prostate cancer (MESH:D011471), infection (MESH:D007239), inflammation (MESH:D007249), Tumor (MESH:D009369), LSCC (MESH:D000077195)
- **Chemicals:** pablizumab (-), calcium (MESH:D002118), cisplatin (MESH:D002945), phosphorus (MESH:D010758), trastuzumab (MESH:D000068878)
- **Species:** Homo sapiens (human, species) [taxon 9606], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12307138/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12307138/full.md

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Source: https://tomesphere.com/paper/PMC12307138