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Regulation, Function, and Expression of Matrix Metalloproteinase-9 in Colon, Lung, and Breast Cancers In Silico and Experimental Methods From Iraqi Metastatic Patients Cover

Regulation, Function, and Expression of Matrix Metalloproteinase-9 in Colon, Lung, and Breast Cancers In Silico and Experimental Methods From Iraqi Metastatic Patients

Open Access
|Jun 2025

Figures & Tables

Table 1:

Anthropometric and clinical features of participants.

CountPercentageP-value
Age groups (years)25–3433.30%P<0.001***
35–4477.80%
45–542730.00%
55–643133.30%
>642425.60%
GenderMales3033.30%P<0.001***
Females6066.70%
GroupsColon cancer1516.70%P<0.001***
Lung cancer3033.30%
Breast cancer3538.90%
Controls1011.10%
StageLate7391.25%P<0.001***
Early78.75%
Response to chemotherapyDisease progression7391.25%P<0.001***
Stable disease78.75%
Figure 1:

Expression and protein analysis of MMP9. (A) Means of the study groups when compared using the Duncan test; a,b Significant differences (p < 0.05). (B) Comparative mean levels of MMP9 among study groups. (C) Sensitivity and specificity graph of colon cancer. (D) Sensitivity and specificity graph of lung cancer. (E) Sensitivity and specificity graph of breast cancer. (F) Differential gene expression of MMP9 in LUAD, COAD, and BRCA tumors. (G) Protein concentrations of MMP9 in each cancer. (H) PPI analysis through STRING. (I) PPI analysis through protein atlas.

Table 2:

Comparative mean levels of MMP9 between late- and early-stage diseases.

StagesnMeanStd deviation
MMP9Late730.430.21
Early70.360.19
P-valueP > 0.05
Table 3:

Comparative mean levels of MMP9 between disease progression and stable disease.

Response to chemotherapynMeanStd deviation
MMP9Disease progression730.410.21
Stable disease70.60.29
P-valueP > 0.05
Table 4:

ROC curve, sensitivity, and specificity of MMP9 in screening cancer patients.

Cancer typeAUCStd errorP-valueCutoffSensitivity %Specificity %
Colon0.8670.0750.05*0.3980%90%
Lung0.690.0930.080.3760%90%
Breast0.5770.0990.460.349%50%
AUC: area under the curve
Table 5:

Genes and pathways implicated with MMP9 in lung, colon, and breast cancers.

Lung cancer
GenesPathways
  • 1. CRKL

  • 2. URGCP

  • 3. SDF-1α

  • 4. SEMA4b

  • 5. ATDC

  • 6. PTTG1

  • 7. FAK

  • 8. TIMP2

  • 9. MMP3

  • 10. TCF2 (HNF1β)

  • 11. KISS1

  • 1. Plasmin-dependent pathway

  • 2. NF-κB

  • 3. CXCR4/ERK/NF-κB

  • 4. EGFR signaling pathway

  • 5. JNK pathways

Colon cancer
GenesPathways
  • 1. TSP1

  • 2. Clusterin (CLU)

  • 3. RasGRF2

  • 4. piwi-like protein 2 (Piwil2)

  • 5. CTHRC1

  • 6. VEGF

  • 7. TIMP2

  • 8. MMP2

  • 9. uPA

  • 1. Src/PI 3-kinase

  • 2. NF-κB pathway

  • 3. MAPK/ERK

  • 4. PI3K/Akt

  • 5. JNK-activated AP-1

  • 6. ROS-dependent ERK1/2

  • 7. p38-MAPK-activated

  • 8. NOTCH1 signaling

Breast cancer
GenesPathways
  • 1. Heregulin- β1(NRG-1)

  • 2. P53

  • 3. CDC42

  • 4. CD44

  • 5. EGF

  • 6. Ets-1

  • 7. TGF β

  • 8. EGFR

  • 9. TNF-β

  • 10. MMP2

  • 11. TIMP1

  • 12. TIMP2

  • 13. Syndecan-2

  • 14. Syndecan-4

  • 1. ERK

  • 2. MAPK

  • 3. PI3K

  • 4. PKC

  • 5. p38 kinase

  • 6. JAK3/ERK

  • 7. PI3K/AKT

  • 8. NF-κB

Table 6:

MMP9 functional partners and their respective scores.

Functional partnersScore
TIMP10.999
TIMP20.998
LCN20.998
CD440.998
THBS10.997
TIMP30.995
CTSG0.992
DMP10.982
ELN0.979
MMP10.974
Table 7:

Top 15 nearest neighbors based on tissue RNA expression.

NeighborDescriptionCorrelationCluster
NKG7Natural killer cell granule protein 70.98426
CLEC12AC-type lectin domain family 12 member A0.982581
CTSWCathepsin W0.982581
NFE2Nuclear factor, erythroid 20.978981
GNLYGranulysin0.977277
PIK3R5Phosphoinositide-3-kinase regulatory subunit 50.977277
RETNResistin0.97546
PADI4Peptidyl arginine deiminase 40.97546
IL18RAPInterleukin 18 receptor accessory protein0.973781
FMNL1Formin-like 10.973781
FOLR3Folate receptor gamma0.96846
SLFN14Schlafen family member 140.96676
ADGRG3Adhesion G protein-coupled receptor G30.96676
HK3Hexokinase 30.963281
GYPEGlycophorin E (MNS blood group)0.963277
DOI: https://doi.org/10.2478/fco-2024-0003 | Journal eISSN: 1792-362X | Journal ISSN: 1792-345X
Language: English
Page range: 19 - 28
Submitted on: Jun 17, 2024
Accepted on: Nov 18, 2024
Published on: Jun 10, 2025
Published by: Helenic Society of Medical Oncology
In partnership with: Paradigm Publishing Services

© 2025 Hamad Ali Hamad, Yamama Farouk Shakir, Omar Tareq Zaidan, Aymen Adnan Rafea, Nur Fariesha Md Hashim, published by Helenic Society of Medical Oncology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.