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Article Open Access

POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer

  • Authors:
    • Ching Hei To
    • Fuda Xie
    • Peiyao Yu
    • Jialin Wu
    • Yang Lyu
    • Bonan Chen
    • Tiejun Feng
    • Hoi Wing Leung
    • Wei Kang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR 999077, P.R. China, Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR 999077, P.R. China
    Copyright: © To et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 82
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    Published online on: July 8, 2025
       https://doi.org/10.3892/mco.2025.2877
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Abstract

Drug resistance significantly impairs the prognosis of patients with gastric cancer (GC). As a key player in the acquisition of drug resistance, understanding the detailed evolution of the GC tumor microenvironment (TME) is crucial for improving therapeutic effectiveness. The clinical significance of markers related to cancer‑associated fibroblast (CAF) proliferation and extracellular matrix remodeling were analyzed using public databases and immunohistochemistry staining on an in‑house cohort of patients with GC. Combining this with single‑cell RNA sequencing data revealed the expression patterns of all candidate markers, highlighting POSTN due to its pronounced upregulation in CAFs and its strong correlation with poor prognosis in patients with GC. Mechanistically, POSTN is directly regulated by the YAP1/TEAD1 co‑transcription factor and is demonstrated to play significant roles in fibroblast proliferation and migration processes. The present study underscores POSTN as a promising marker for predicting GC prognosis and a powerful regulator that can augment the tumorigenic phenotypes of CAFs, providing a potential target to mitigate CAF‑originated drug resistance.
View Figures

Figure 1

Expression distribution of POSTN in
the GC primary samples in a single-cell resolution. (A) The UMAP
landscape of all cell types within GC tumor microenvironment. (B)
POSTN demonstrates exclusive upregulation in fibroblasts.
POSTN, periostin; GC, gastric cancer; pDC, plasmatocytoid dendritic
cells.

Figure 2

POSTN expression pattern among
molecular subtypes of GC CAFs. (A) The UMAP landscape of GC CAFs
with four subtypes. (B) POSTN exhibits dominant expression
in matrix-remodeling CAFs, along with a minor cluster in
inflammatory CAFs. POSTN, periostin; GC, gastric cancer; CAFs,
cancer-associated fibroblasts.

Figure 3

Kaplan-Meier survival curves based on
the mRNA expression level of periostin in (A) all patients with GC;
(B) patients with intestinal type GC; and (C) patients with diffuse
type GC from TCGA cohort, respectively. GC, gastric cancer; TCGA,
The Cancer Genome Atlas.

Figure 4

Representative immunohistochemical
images of negative and positive POSTN gastric cancer cases. (A)
POSTN-negative cases. (B) POSTN-positive cases. Scale bar, 100 µm
for low magnification and 10 µm for high magnification. POSTN,
periostin.

Figure 5

Kaplan-Meier survival curves based on
the protein expression level of periostin in (A) all patients with
GC; (B) patients with intestinal type GC; and (C) patients with
diffuse type GC from the Hong Kong cohort, respectively. GC,
gastric cancer.

Figure 6

Bioinformatic analysis revealing the
potential of POSTN in extracellular matrix remodeling by enhancing
fibroblast proliferation and migration. (A) Volcano plot
demonstrating the differentially expressed genes between
POSTN+ and POSTN-samples in TCGA cohort. (B) Pearson's
correlation heatmap demonstrates the relevance between the
expression level of POSTN and fibroblast proliferation- and
migration-related markers. (C) Normalized expression heatmap
showcasing the relative expression level of the same genes in
POSTN+ and POSTN-samples. (D) Gene Ontology biological
processes enriched in POSTN+ samples. (E) KEGG pathways
enriched in POSTN+ samples by GSEA. (F) Deletion of
POSTN significantly inhibited the cell viability of CAFs. (G and H)
The invasion ability was impaired by POSTN deletion. (I) The
expression levels of pRb and cyclin D1 were downregulated in
POSTN-deleted CAFs, while p21 and cleaved-PARP demonstrated
upregulated expression. (J) Scheme of the in vivo xenograft
formation assay (Generated by BioRender.com). (K) Cancer cells mixed with
POSTN-deleted CAFs generated smaller xenografts.
*P<0.05 and ***P<0.001. POSTN,
periostin; TCGA, The Cancer Genome Atlas; KEGG, Kyoto Encyclopedia
of Genes and Genomes; GSEA, Gene Set Enrichment Analysis; CAFs,
cancer-associated fibroblasts; si-, small interfering; sh-, short
hairpin.

Figure 7

POSTN is directly regulated by the
YAP1-TEAD1 transcription complex. (A) Pearson's correlation
analysis between the mRNA expression levels of YAP1-POSTN and
TEAD1-POSTN. (B) Presence prediction of YAP1-TEAD1 binding motif on
the promoter region of POSTN. (C and D) Chronological correlation
between the expression levels of POSTN, YAP1 signaling signatures
and cell proliferation/migration marker genes. (E) Distribution of
YAP1-TEAD1-POSTN-positive CAFs in GC single-cell RNA sequencing
atlas. (F and G) Western blot analysis on the YAP1- and
TEAD1-knockdown CAFs. POSTN, periostin; CAFs, cancer-associated
fibroblasts
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Copy and paste a formatted citation
Spandidos Publications style
To CH, Xie F, Yu P, Wu J, Lyu Y, Chen B, Feng T, Leung HW and Kang W: POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer. Mol Clin Oncol 23: 82, 2025.
APA
To, C.H., Xie, F., Yu, P., Wu, J., Lyu, Y., Chen, B. ... Kang, W. (2025). POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer. Molecular and Clinical Oncology, 23, 82. https://doi.org/10.3892/mco.2025.2877
MLA
To, C. H., Xie, F., Yu, P., Wu, J., Lyu, Y., Chen, B., Feng, T., Leung, H. W., Kang, W."POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer". Molecular and Clinical Oncology 23.3 (2025): 82.
Chicago
To, C. H., Xie, F., Yu, P., Wu, J., Lyu, Y., Chen, B., Feng, T., Leung, H. W., Kang, W."POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer". Molecular and Clinical Oncology 23, no. 3 (2025): 82. https://doi.org/10.3892/mco.2025.2877
Copy and paste a formatted citation
x
Spandidos Publications style
To CH, Xie F, Yu P, Wu J, Lyu Y, Chen B, Feng T, Leung HW and Kang W: POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer. Mol Clin Oncol 23: 82, 2025.
APA
To, C.H., Xie, F., Yu, P., Wu, J., Lyu, Y., Chen, B. ... Kang, W. (2025). POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer. Molecular and Clinical Oncology, 23, 82. https://doi.org/10.3892/mco.2025.2877
MLA
To, C. H., Xie, F., Yu, P., Wu, J., Lyu, Y., Chen, B., Feng, T., Leung, H. W., Kang, W."POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer". Molecular and Clinical Oncology 23.3 (2025): 82.
Chicago
To, C. H., Xie, F., Yu, P., Wu, J., Lyu, Y., Chen, B., Feng, T., Leung, H. W., Kang, W."POSTN is exclusively activated in cancer‑associated fibroblasts and leads to unfavorable prognosis of patients with gastric cancer". Molecular and Clinical Oncology 23, no. 3 (2025): 82. https://doi.org/10.3892/mco.2025.2877
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