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Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis

  • Authors:
    • Biran Ding
    • Yiqiu Wan
    • Yao Wu
    • Zhan Zhang
    • Ying Ma
    • Zuo Wang
    • Runqiu Jiang
    • Tao Li
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230011, P.R. China, Department of Clinical Laboratory, Anhui Feixi County Traditional Chinese Medicine Hospital, Feixi, Anhui 231200, P.R. China, Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230011, P.R. China, Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230011, P.R. China
    Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 107
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    Published online on: January 14, 2026
       https://doi.org/10.3892/ol.2026.15460
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Abstract

Aggressive invasion and metastatic dissemination of gastric cancer (GC) are two major clinical challenges that frequently arise following standard treatments, markedly compromising patient outcomes. Elucidating the molecular drivers of GC progression would be key to developing effective therapeutic strategies. The present study employed an integrated approach combining bioinformatics analysis and immunohistochemical (IHC) validation to identify the key molecular players in GC metastasis. The Cancer Genome Atlas (TCGA) database analysis demonstrated marked upregulation of both epidermal growth factor receptor (EGFR) and matrix metalloproteinase 7 (MMP7) in gastric adenocarcinoma and elevated expression levels notably associated with poor patient prognosis. MMP7 expression exhibited a particularly robust association with metastatic progression, highlighting its potential role in facilitating tumor dissemination and experimental validation using IHC analysis of clinical specimens confirmed the coordinated involvement of both phosphorylated (p)‑EGFR and MMP7 in metastatic processes. Notably, the present study identified a positive correlation between p‑EGFR and MMP7 expression, suggesting a potential mechanistic interplay between these molecules in driving GC metastasis. These findings provide notable evidence that p‑EGFR and MMP7 collectively contribute to GC progression and metastasis. The correlation between these markers offered novel insights into potential cooperative signaling pathways and presented a rational basis for the development of dual‑targeted therapeutic approaches. The present study established a key foundation for future research aimed at disrupting the metastatic pathways in GC through targeted inhibition of p‑EGFR and MMP7.

View Figures

Figure 1

Bioinformatics analysis of MMP7
expression in gastric cancer. (A) Gene profile of upregulation in
GC, showing the top 25 upregulated genes. (B) TCGA analysis: MMP7
expression in GC and normal tissue. The error bars indicate the
non-outlier data range, the box shows the interquartile range and
the internal line marks the median. Individual dots represent
outliers. (C) Survival prognosis of patients with GC based on MMP7
expression: An analysis of TCGA data. MMP7, matrix
metalloproteinase 7; GC, gastric cancer; TCGA, The Cancer Genome
Atlas; STAD, stomach adenocarcinoma; HR, hazard ratio; TPM,
transcripts per million.

Figure 2

Bioinformatics analysis of MMP7
expression in gastric cancer. (A) Expression level of MMP7 in
different stages of GC. (B) Expression level of MMP7 in different
grades of GC and normal tissues. (C) Expression level of MMP7 in
male and female patients with GC. (D) Expression level of MMP7 in
different lymph node states of GC. For all box plots, error bars
depict the variability of the data outside the interquartile range,
extending to the farthest non-outlier data points. The box shows
the interquartile range and the internal line marks the median.
MMP7, matrix metalloproteinase 7; GC, gastric cancer; STAD, stomach
adenocarcinoma.

Figure 3

Bioinformatics analysis of EGFR
expression in gastric cancer. Upregulation of EGFR in gastric
adenocarcinoma is associated with worse patient prognosis. (A)
Expression level of EGFR between normal and GC samples. The box
plot shows the median, interquartile range and full data range
(error bars). Individual data points are overlaid. (B) Analysis of
survival prognosis of EGFR in GC. EGFR, epidermal growth factor
receptor; TCGA, The Cancer Genome Atlas; STAD, stomach
adenocarcinoma; HR, hazard ratio.

Figure 4

Expression levels of MMP7 and p-EGFR
are higher in metastatic gastric adenocarcinoma tissues. (A) IHC
and H&E analysis for the differential expression levels of
p-EGFR and MMP7 in metastatic and non-metastatic GC and normal
tissues. Patients 1–2 were classified as non-metastatic, while
patients 3–4 were categorized as metastatic (scale bar, 200 µm).
(B) Quantitative analysis of p-EGFR expression (AOD) using IHC
staining between metastatic (n=17) and non-metastatic (n=15).
****P<0.0001. (C) Quantitative analysis of MMP7 expression (AOD)
using IHC staining between metastatic (n=17) and non-metastatic
(n=15). ****P<0.0001. Error bars represent the SD from the mean
of three independent experiments. MMP7, matrix metalloproteinase 7;
p-EGFR, phosphorylated-epidermal growth factor receptor; GC,
gastric cancer; AOD, average optical density; IHC,
immunohistochemical; H&E, hematoxylin-eosin.

Figure 5

p-EGFR and MMP7 are positively
correlated in gastric adenocarcinoma tissue. (A) IHC analysis for
p-EGFR and MMP7 expression and H&E staining in GC tissues and
normal tissues (scale bar, 200 µm). (B) Quantitative analysis of
p-EGFR expression (AOD) using IHC staining between GC and
corresponding normal tissues. (C) Quantitative analysis of MMP7
expression (AOD) using IHC staining between GC and corresponding
normal tissues. (D) Correlation between p-EGFR and MMP7 expression
in GC tissues, with the orange part representing a 95% confidence
interval. ****P<0.0001. Error bars represent the SD from the
mean of three independent experiments. MMP7, matrix
metalloproteinase 7; p-EGFR, phosphorylated-epidermal growth factor
receptor; GC, gastric cancer; AOD, average optical density; IHC,
immunohistochemical; HE, hematoxylin-eosin.
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Copy and paste a formatted citation
Spandidos Publications style
Ding B, Wan Y, Wu Y, Zhang Z, Ma Y, Wang Z, Jiang R and Li T: <p>Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis</p>. Oncol Lett 31: 107, 2026.
APA
Ding, B., Wan, Y., Wu, Y., Zhang, Z., Ma, Y., Wang, Z. ... Li, T. (2026). <p>Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis</p>. Oncology Letters, 31, 107. https://doi.org/10.3892/ol.2026.15460
MLA
Ding, B., Wan, Y., Wu, Y., Zhang, Z., Ma, Y., Wang, Z., Jiang, R., Li, T."<p>Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis</p>". Oncology Letters 31.3 (2026): 107.
Chicago
Ding, B., Wan, Y., Wu, Y., Zhang, Z., Ma, Y., Wang, Z., Jiang, R., Li, T."<p>Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis</p>". Oncology Letters 31, no. 3 (2026): 107. https://doi.org/10.3892/ol.2026.15460
Copy and paste a formatted citation
x
Spandidos Publications style
Ding B, Wan Y, Wu Y, Zhang Z, Ma Y, Wang Z, Jiang R and Li T: <p>Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis</p>. Oncol Lett 31: 107, 2026.
APA
Ding, B., Wan, Y., Wu, Y., Zhang, Z., Ma, Y., Wang, Z. ... Li, T. (2026). <p>Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis</p>. Oncology Letters, 31, 107. https://doi.org/10.3892/ol.2026.15460
MLA
Ding, B., Wan, Y., Wu, Y., Zhang, Z., Ma, Y., Wang, Z., Jiang, R., Li, T."<p>Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis</p>". Oncology Letters 31.3 (2026): 107.
Chicago
Ding, B., Wan, Y., Wu, Y., Zhang, Z., Ma, Y., Wang, Z., Jiang, R., Li, T."<p>Phosphorylated‑EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis</p>". Oncology Letters 31, no. 3 (2026): 107. https://doi.org/10.3892/ol.2026.15460
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