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TNM staging for GIT cancers is correlated with the level of MMPs and TGF-β1

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Abstract

Gastrointestinal (GIT) cancers represent the third common cancers worldwide, characterized by rapid progression and higher mortality rate. Matrix metalloproteinases (MMPs) play an important role in cancer metastases. The present study was conducted to estimate and evaluate the role of MMP-7, -9, -10 and -12 and TGF β1 along with conventional biomarkers (CEA and CA19-9) in gastric (GC), pancreatic (PC) and colorectal cancer (CRC) staging system according to tumor size (T), included lymph node (N) and metastasis (M). Seventy-five patients were divided into GC group (n = 25), PC group (n = 25), CRC group (n = 25) and twenty-five healthy subjects (control group). Serum levels of MMP-7, -10 and -12 were assayed simultaneously using luminex multiplex technique. Also, MMP-9, TGF-β1, CA19-9 and CEA were determined by ELISA. MMP-7,-9,-10, -12, TGF-β1 and CEA levels were significantly (p < 0.001) higher in GIT cancer groups compared with control. CA19-9 was significantly (p < 0.001) higher in PC and CRC groups compared with control. MMP-9 was positively correlated with TNM staging in PC patients. MMP-12 was negatively correlated with T in PC and positively correlated with M in CRC group. CA 19-9 was positively correlated with M grade in CRC. Depending on the estimated cutoff values of area under receiver curve; CA19-9 and MMP-7 were excellent diagnostic markers in PC, CEA and MMP-7 were excellent in CRC, and MMP-7 and MMP-9 were excellent in GC. Our findings indicated the clinical utility of MMPs in diagnosis and TNM staging of GIT cancers along with CEA and CA19-9.

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Abbreviations

GIT:

Gastrointestinal

MMP:

Matrix metalloproteinases

PC:

Pancreatic cancer

CRC:

Colorectal cancer

GC:

Gastric cancer

HCC:

Hepatocellular carcinoma

VEGF:

Vascular endothelial growth factor

EGF:

Epidermal growth factor

TGF-β1:

Transforming growth factor beta-1

TIMP:

Tissue inhibitors of metalloproteinases

CEA:

Carcinoembryonic antigen

CA19-9:

Carbohydrate antigen 19-9

ELISA:

Enzyme-linked immunosorbent assay

ROC:

Receiver operating characteristic

AUC:

Area under the curve

DSe:

Diagnostic sensitivity

DSp:

Diagnostic specificity

EGFR:

Epidermal growth factor receptor

MEK–ERK:

Mitogen-activated protein kinase–extracellular signal regulated protein kinase

TJ:

Tight junctions

S100A4:

S100 calcium-binding protein A4

PAI:

Plasminogen activator inhibitor

HB-EGF:

Heparin-binding epidermal growth factor

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Acknowledgements

The authors gratefully acknowledged the medical staff of Oncology center, Mansoura University, Mansoura, Egypt, for their help in collecting patient’s data and samples for analysis.

Funding

The research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors funded the research.

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Author notes

  1. Nahla E. El-Ashmawy, Naglaa F. Khedr, Mohamed G. Mansour and Ghada M. Al-Ashmawy have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt

    Nahla E. El-Ashmawy, Naglaa F. Khedr & Ghada M. Al-Ashmawy

  2. Clinical Pharmacy Department, Oncology Center, Mansoura University, Mansoura, 35516, Egypt

    Mohamed G. Mansour

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  1. Nahla E. El-Ashmawy
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  2. Naglaa F. Khedr
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Contributions

El-Ashmawy NE conceived the presented idea, analyzed the data and approved the manuscript in final version for publication. Khedr NF planned the experiments, wrote and reviewed the manuscript and approved it for publication. Al-Ashmawy GM designed the study, reviewed the manuscript and approved it for publication. Mansour MG conducted the research, drafted the manuscript and approved it for final approval.

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Correspondence to Naglaa F. Khedr or Mohamed G. Mansour.

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El-Ashmawy, N.E., Khedr, N.F., Mansour, M.G. et al. TNM staging for GIT cancers is correlated with the level of MMPs and TGF-β1. Clin Exp Med 20, 545–555 (2020). https://doi.org/10.1007/s10238-020-00651-2

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