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TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways

  • Authors:
    • Jiming Gu
    • Dongming Zhu
    • Fan Chen
    • Tongguo Shi
    • Suhua Xia
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China, Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
    Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 36
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    Published online on: November 18, 2025
       https://doi.org/10.3892/ol.2025.15390
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Abstract

Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is highly expressed in several cancer types, including lung, brain, prostate, breast and colon cancer, and is associated with a poor prognosis. However, further comprehensive research is required. The present study aimed to explore TIMP1 expression in colorectal cancer (CRC), its prognostic relationship and its connection to tumor immunity, using data from The Cancer Genome Atlas database and clinical samples. The present study evaluated the correlation between TIMP1 expression and CRC by integrating RNA sequencing data, and clinical information from The Cancer Genome Atlas (TCGA), UALCAN and GEPIA2 databases, as well as clinical samples. The findings demonstrated that TIMP1 is highly expressed in CRC tissues and is associated with a poor prognosis. Notably, high TIMP1 levels in CRC were positively correlated with the numbers of CD4+ and CD8+ T cells based on the immune scores, as well as with tumor mutation burden/microsatellite instability. In addition, TIMP1 may be involved in pathways such as those associated with epithelial‑mesenchymal transition, extracellular matrix‑related processes, collagen formation, angiogenesis, apoptosis and ferroptosis. TIMP1 may also be involved in pathways associated with genes upregulated by reactive oxygen species, tumor inflammation and in the TGF‑β signaling pathway. Overall, the results indicate that TIMP1 is associated with prognosis, tumor immunity and several pathways in CRC, potentially offering novel theoretical insights for the treatment of CRC.
View Figures

Figure 1

TIMP1 expression in several types of
cancer. (A) UALCAN database was used to analyze the expression
levels of TIMP1 in several types of pan-cancer tissues (indicated
by the red box) and their corresponding normal tissues (indicated
by the blue box). (B) Expression of TIMP1 was significantly
upregulated in colon cancer tissues compared with that in normal
tissues. (C) Expression level of TIMP1 was significantly
upregulated in colon tissues compared with that in normal tissues,
based on TCGA data from the Gene Expression Profiling Interactive
Analysis 2.0 database. (D) Expression level of TIMP1 was
significantly upregulated in colon tissues (G2) compared with in
normal tissues (G1) in the GSE24550 dataset. (E) Protein expression
of TIMP1 in colon tissues from CPTAC data based on the UALCAN
database. *P<0.05; ****P<0.0001. TIMP1, tissue inhibitor of
matrix metalloproteinase 1; UALCAN, University of Alabama at
Birmingham CANcer data analysis Portal; TCGA, The Cancer Genome
Atlas; CPTAC, Clinical Proteomic Tumor Analysis Consortium; TPM,
transcripts per million; G, grade; COAD, colon adenocarcinoma.

Figure 2

Association between TIMP1 expression
and survival prognosis of patients with CRC. (A) Association
between TIMP1 expression and the overall survival of patients with
CRC was analyzed using the GEPIA 2.0 database. (B) Association
between TIMP1 expression and the overall survival of patients with
colon cancer was analyzed using the University of Alabama at
Birmingham CANcer data analysis Portal database. (C) Kaplan-Meier
survival curve for TIMP1 in CRC-The Cancer Genome Atlas data, with
different groups compared using the log-rank test. (D) Association
between TIMP1 expression and the disease-free survival of patients
with CRC was analyzed using the GEPIA 2.0 database. TIMP1, tissue
inhibitor of matrix metalloproteinase 1; CRC, colorectal cancer;
GEPIA, Gene Expression Profiling Interactive Analysis; HR, hazard
ratio; CI, confidence interval; COAD, colon adenocarcinoma.

Figure 3

TIMP1 serves as a prognostic factor
for overall survival in CRC. (A) Univariate and (B) multivariate
Cox analyses of TCGA data of patients with CRC for TIMP1 expression
and clinical characteristics. (C) Nomogram formulated to predict
1-year overall survival for patients with CRC from TCGA data. (D)
Calibration curve for the overall survival nomogram model in the
discovery cohort, where the diagonal dashed line denotes the ideal
nomogram, and the red line represent the observed 1-year nomograms.
TIMP1, tissue inhibitor of matrix metalloproteinase 1; CRC,
colorectal cancer; TCGA, The Cancer Genome Atlas; HR, hazard ratio;
CI, confidence interval; p, pathological; T, tumor; N, node; M,
metastasis.

Figure 4

Association between TIMP1 expression
and immunity in CRC. Heatmap illustrates the correlation analysis
of TIMP1 expression with (A) TIMER and (B) EPIC scores. Red
signifies a positive correlation, whilst blue indicates a negative
correlation. The intensity of the red or blue color reflects the
strength of the correlation, and the size of the circle indicates
the magnitude of the correlation. In the schematic, a red line
denotes a negative correlation between model scores/gene expression
and immune scores, whereas a green line denotes a positive
correlation. (C) Spearman's correlation analysis of TIMP1
expression with CD4+ and CD8+ T cells in CRC
from The Cancer Genome Atlas database. (D) Spearman's correlation
analysis of TIMP1 expression with TMB/MSI score distribution is
shown. TIMP1, tissue inhibitor of matrix metalloproteinase 1; CRC,
colorectal cancer; TMB, tumor mutation burden; MSI,/microsatellite
instability; NK, natural killer.

Figure 5

Correlation of TIMP1 and signaling
pathways in CRC. Spearman's correlation analysis plots reveal the
correlation between pathway scores and TIMP1 expression in CRC
samples from The Cancer Genome Atlas database. TIMP1, tissue
inhibitor of matrix metalloproteinase 1; CRC, colorectal cancer;
TPM, transcripts per million; EMT, epithelial-mesenchymal
transition; ECM, extracellular matrix.

Figure 6

TIMP1 protein expression in the
colorectal cancer cohort in the present study. (A) Representative
images of IHC analysis of TIMP1 protein expression of NAT (n=78)
and CC (n=78) tissue sections. Scale bar, 100 µm. (B) TIMP1 protein
expression based on their staining index in NAT and CC specimens.
(C) Patients with CC with high TIMP1 expression (IHC score ≥4) had
a significantly worse prognosis than patients with low TIMP1
expression (IHC score <4). ***P<0.001. TIMP1, tissue
inhibitor of matrix metalloproteinase 1; IHC, immunohistochemistry;
NAT, nonmalignant adjacent tissues; CC, colon cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Gu J, Zhu D, Chen F, Shi T and Xia S: TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways. Oncol Lett 31: 36, 2026.
APA
Gu, J., Zhu, D., Chen, F., Shi, T., & Xia, S. (2026). TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways. Oncology Letters, 31, 36. https://doi.org/10.3892/ol.2025.15390
MLA
Gu, J., Zhu, D., Chen, F., Shi, T., Xia, S."TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways". Oncology Letters 31.1 (2026): 36.
Chicago
Gu, J., Zhu, D., Chen, F., Shi, T., Xia, S."TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways". Oncology Letters 31, no. 1 (2026): 36. https://doi.org/10.3892/ol.2025.15390
Copy and paste a formatted citation
x
Spandidos Publications style
Gu J, Zhu D, Chen F, Shi T and Xia S: TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways. Oncol Lett 31: 36, 2026.
APA
Gu, J., Zhu, D., Chen, F., Shi, T., & Xia, S. (2026). TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways. Oncology Letters, 31, 36. https://doi.org/10.3892/ol.2025.15390
MLA
Gu, J., Zhu, D., Chen, F., Shi, T., Xia, S."TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways". Oncology Letters 31.1 (2026): 36.
Chicago
Gu, J., Zhu, D., Chen, F., Shi, T., Xia, S."TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways". Oncology Letters 31, no. 1 (2026): 36. https://doi.org/10.3892/ol.2025.15390
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