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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

Hamad Ali Hamad

Hamad Ali Hamad

  • Department of Pathological Analysis, College of Applied Sciences, University of FallujahAlanbar, Iraq
  • Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra MalaysiaSerdang, Malaysia
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Hamad, Hamad Ali
, 
Yamama Farouk Shakir

Yamama Farouk Shakir

Ibn Sina University of Medical and Pharmaceutical SciencesBaghdad, Iraq
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Shakir, Yamama Farouk
, 
Omar Tareq Zaidan

Omar Tareq Zaidan

Department of Applied Chemistry, College of Applied Sciences, University of FallujahAlanbar, Iraq
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Zaidan, Omar Tareq
, 
Aymen Adnan Rafea

Aymen Adnan Rafea

Department of Medical Oncology, Anbar Cancer Centre, Anbar Health DirectorateIraq
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Rafea, Aymen Adnan
 und 
Nur Fariesha Md Hashim

Nur Fariesha Md Hashim

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra MalaysiaSerdang, Malaysia
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Md Hashim, Nur Fariesha
  
10. Juni 2025
Regulation, Function, and Expression of Matrix Metalloproteinase-9 in Colon, Lung, and Breast Cancers In Silico and Experimental Methods From Iraqi Metastatic Patients's Cover Image
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Artikel-Kategorie: Research Article
Online veröffentlicht: 10. Juni 2025
Seitenbereich: 19 - 28
Eingereicht: 17. Juni 2024
Akzeptiert: 18. Nov. 2024
DOI: https://doi.org/10.2478/fco-2024-0003
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© 2024 Hamad Ali Hamad et al., published by Sciendo
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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.
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.

MMP9 functional partners and their respective scores_

Functional partners Score
TIMP1 0.999
TIMP2 0.998
LCN2 0.998
CD44 0.998
THBS1 0.997
TIMP3 0.995
CTSG 0.992
DMP1 0.982
ELN 0.979
MMP1 0.974

Comparative mean levels of MMP9 between disease progression and stable disease_

Response to chemotherapy n Mean Std deviation
MMP9 Disease progression 73 0.41 0.21
Stable disease 7 0.6 0.29
P-value P > 0.05

ROC curve, sensitivity, and specificity of MMP9 in screening cancer patients_

Cancer type AUC Std error P-value Cutoff Sensitivity % Specificity %
Colon 0.867 0.075 0.05* 0.39 80% 90%
Lung 0.69 0.093 0.08 0.37 60% 90%
Breast 0.577 0.099 0.46 0.3 49% 50%
AUC: area under the curve

Anthropometric and clinical features of participants_

Count Percentage P-value
Age groups (years) 25–34 3 3.30% P<0.001***
35–44 7 7.80%
45–54 27 30.00%
55–64 31 33.30%
>64 24 25.60%
Gender Males 30 33.30% P<0.001***
Females 60 66.70%
Groups Colon cancer 15 16.70% P<0.001***
Lung cancer 30 33.30%
Breast cancer 35 38.90%
Controls 10 11.10%
Stage Late 73 91.25% P<0.001***
Early 7 8.75%
Response to chemotherapy Disease progression 73 91.25% P<0.001***
Stable disease 7 8.75%

Top 15 nearest neighbors based on tissue RNA expression_

Neighbor Description Correlation Cluster
NKG7 Natural killer cell granule protein 7 0.9842 6
CLEC12A C-type lectin domain family 12 member A 0.9825 81
CTSW Cathepsin W 0.9825 81
NFE2 Nuclear factor, erythroid 2 0.9789 81
GNLY Granulysin 0.9772 77
PIK3R5 Phosphoinositide-3-kinase regulatory subunit 5 0.9772 77
RETN Resistin 0.9754 6
PADI4 Peptidyl arginine deiminase 4 0.9754 6
IL18RAP Interleukin 18 receptor accessory protein 0.9737 81
FMNL1 Formin-like 1 0.9737 81
FOLR3 Folate receptor gamma 0.9684 6
SLFN14 Schlafen family member 14 0.9667 6
ADGRG3 Adhesion G protein-coupled receptor G3 0.9667 6
HK3 Hexokinase 3 0.9632 81
GYPE Glycophorin E (MNS blood group) 0.9632 77

Comparative mean levels of MMP9 between late- and early-stage diseases_

Stages n Mean Std deviation
MMP9 Late 73 0.43 0.21
Early 7 0.36 0.19
P-value P > 0.05

Genes and pathways implicated with MMP9 in lung, colon, and breast cancers_

Lung cancer
Genes Pathways

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
Genes Pathways

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
Genes Pathways

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
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