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Article Open Access

High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma

  • Authors:
    • Jingjing Li
    • Zhiqiang Zong
    • Jian Shen
    • Jiahao Wang
    • Xuan Zhou
    • Wei Shi
    • Jia Li
    • Hong Zhao
    • Yunwen Yan
    • Fanfan Li
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Department of Radiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Department of Breast Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].
  • Article Number: 81
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    Published online on: December 18, 2025
       https://doi.org/10.3892/ol.2025.15434
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Abstract

Breast invasive carcinoma (BRCA) is the most common type of cancer affecting women worldwide. Biomarkers such as estrogen receptor, progesterone receptor and HER2 are currently utilized in clinical practice for breast cancer diagnosis; yet their sensitivity and specificity remain limited. However, Ras‑GTPase‑activating protein SH3 domain‑binding protein 1 (G3BP1), an RNA‑binding protein, has been implicated in tumor progression in various cancers, yet its clinical relevance and mechanistic role in BRCA still remain unclear. The present study integrated multi‑omics data analysis and experimental validation to address this. G3BP1 mRNA and protein expression levels in BRCA were analyzed using The Cancer Genome Atlas, Tumor Immune Estimation Resource (TIMER) and Clinical Proteomic Tumor Analysis Consortium databases. Kaplan‑Meier survival analysis and Cox regression were employed to evaluate the prognostic value of G3BP1. Gene set enrichment analysis (GSEA) was performed to identify associated signaling pathways and immune cell infiltration correlations were assessed using CIBERSORT and TIMER. Additionally, 38 samples of BRCA and adjacent normal tissue were collected for immunohistochemical (IHC) validation and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. G3BP1 was significantly upregulated in BRCA tissues at both mRNA and protein levels (P<0.05). High G3BP1 expression was associated with the advanced cancer lymph node stage (P=0.005) and a poor prognosis [overall survival, disease‑free survival (DFS), distant metastasis‑free survival and post‑progression survival; all P<0.05]. Differential gene analysis identified 67 upregulated and 9 downregulated genes. GSEA revealed G3BP1 enrichment in key pathways such as PI3K/AKT/mTOR signaling and ubiquitin‑mediated proteolysis. Immune analysis showed a significant positive association between G3BP1 and M2 macrophage infiltration (P<0.05) and a significant negative association between G3BP1 and CD8+ T cells (P<0.05). IHC confirmed higher G3BP1 expression in BRCA compared with normal tissues (P<0.001), with an area under the ROC curve (AUC) of 0.777 and a 5‑year DFS prediction AUC of 0.730. The present findings indicate that G3BP1 is a potential independent prognostic biomarker for BRCA. Its upregulation promotes tumor progression by activating the PI3K/AKT/mTOR signaling pathway and modulating the tumor immune microenvironment. These findings provide a theoretical foundation for targeting G3BP1 in BRCA diagnosis and immunotherapy.
View Figures

Figure 1

G3BP1 expression profile for both
transcriptional and protein hierarchies in human tissues. (A) The
G3BP1 mRNA expression in pan-cancers from the TIMER database. (B)
Comparison of G3BP1 expression in normal and breast tumor tissues
in TCGA database. (C) Comparison of G3BP1 expression in normal and
breast tumor tissues in the CPTAC database, Z-value shows standard
deviations from the median of BRCA samples. (D)
Immunohistochemistry of G3BP1 in normal and cancerous breast
tissues in the Human Protein Atlas dataset. *P<0.05;
**P<0.01; ***P<0.001. TIMER, Tumor Immune Estimation
Resource; CPTAC, Clinical Proteomic Tumor Analysis Consortium;
BRCA, breast invasive carcinoma; TCGA, The Cancer Genome Atlas;
G3BP1, Ras-GTPase-activating protein SH3 domain-binding protein 1;
TPM, transcript per million.

Figure 2

Association between G3BP1 expression
levels and clinicopathological characteristics in BRCA. (A) T
stage, (B) N stage, (C) pathological stage, (D) M stage, (E) age
and (F) sex. T, tumor; N, lymph node; M, metastasis; G3BP1,
Ras-GTPase-activating protein SH3 domain-binding protein 1.

Figure 3

High G3BP1 expression is closely
related to a poor prognosis in BRCA. (A) The survival analysis
results from TCGA database showed that overall survival of the high
expression group was markedly worse compared with the low
expression group. (B) The survival analysis results from
Kaplan-Meier plotter database showed that DFS of the high
expression group was also markedly worse compared with the low
expression group. (C) The survival analysis results from
Kaplan-Meier plotter database showed that DMFS of the high
expression group was also markedly worse compared with the low
expression group. (D) The survival analysis results from
Kaplan-Meier plotter database showed that PPS of the high
expression group was also markedly worse compared with the low
expression group. G3BP1, Ras-GTPase-activating protein SH3
domain-binding protein 1; BRCA, breast invasive carcinoma; TCGA,
The Cancer Genome Atlas; DFS, disease free survival; DMFS, distant
metastasis-free survival; PPS, post-progression survival.

Figure 4

Multi-dimensional profiling of
G3BP1-associated transcriptional dysregulation in breast invasive
carcinoma. (A) Differential gene screening via volcano plot. (B)
Stratified gene expression patterns by heatmap. (C) Multi-pathway
gene set enrichment analysis including GO CC, GO BP, GO MF, KEGG,
Hallmark and ImmuneSigDB. GO, Gene Ontology; CC, cellular
components; BP, biological processes; MF, molecular functions;
KEGG, Kyoto Encyclopedia of Genes and Genomes, G3BP1;
Ras-GTPase-activating protein SH3 domain-binding protein 1; NES,
normalized enrichment score; NP, nominal P-value.

Figure 5

Correlation between immune cell
infiltration and G3BP1 in BRCA. (A) Correlation between G3BP1
expression level in BRCA and infiltration of 22 immune cells.
Relationship between G3BP1 expression and infiltration of (B) B
cells, (C) T cells CD4+, (D) T cells CD8+,
(E) neutrophils, (F) macrophages and (G) DCs in the TIMER database.
*P<0.05 and ***P<0.001. BRCA, breast invasive carcinoma; DC,
dendritic cells; G3BP1, Ras-GTPase-activating protein SH3
domain-binding protein 1.

Figure 6

G3BP1 expression, prognosis and
time-dependent ROC for BRCA. (A and B) G3BP1 protein was more
expressed in BRCA compared with normal tissues, analyzed using
immunohistochemistry. (C) The diagnostic value of G3BP1 expression
in BRCA. (D) Kaplan-Meier survival analysis showed that
upregulation G3BP1 had adverse DFS. (E) Time-dependent ROC curve of
G3BP1 expression in predicting 1-, 3- and 5-year DFS.
***P<0.001. BRCA, breast invasive carcinoma; DFS, disease free
survival; AUC, area under curve; G3BP1, Ras-GTPase-activating
protein SH3 domain-binding protein 1; ROC, receiver operating
characteristic; TPR, true positive rate; FPR, false positive
rate.
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Copy and paste a formatted citation
Spandidos Publications style
Li J, Zong Z, Shen J, Wang J, Zhou X, Shi W, Li J, Zhao H, Yan Y, Li F, Li F, et al: High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma. Oncol Lett 31: 81, 2026.
APA
Li, J., Zong, Z., Shen, J., Wang, J., Zhou, X., Shi, W. ... Li, F. (2026). High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma. Oncology Letters, 31, 81. https://doi.org/10.3892/ol.2025.15434
MLA
Li, J., Zong, Z., Shen, J., Wang, J., Zhou, X., Shi, W., Li, J., Zhao, H., Yan, Y., Li, F."High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma". Oncology Letters 31.2 (2026): 81.
Chicago
Li, J., Zong, Z., Shen, J., Wang, J., Zhou, X., Shi, W., Li, J., Zhao, H., Yan, Y., Li, F."High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma". Oncology Letters 31, no. 2 (2026): 81. https://doi.org/10.3892/ol.2025.15434
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Zong Z, Shen J, Wang J, Zhou X, Shi W, Li J, Zhao H, Yan Y, Li F, Li F, et al: High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma. Oncol Lett 31: 81, 2026.
APA
Li, J., Zong, Z., Shen, J., Wang, J., Zhou, X., Shi, W. ... Li, F. (2026). High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma. Oncology Letters, 31, 81. https://doi.org/10.3892/ol.2025.15434
MLA
Li, J., Zong, Z., Shen, J., Wang, J., Zhou, X., Shi, W., Li, J., Zhao, H., Yan, Y., Li, F."High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma". Oncology Letters 31.2 (2026): 81.
Chicago
Li, J., Zong, Z., Shen, J., Wang, J., Zhou, X., Shi, W., Li, J., Zhao, H., Yan, Y., Li, F."High expression of G3BP1 is associated with poor prognosis in breast invasive carcinoma". Oncology Letters 31, no. 2 (2026): 81. https://doi.org/10.3892/ol.2025.15434
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