Correlation of TIMP1-MMP2/MMP9 Gene Expression Axis Changes with Treatment Efficacy and Survival of NSCLC Patients

Sep 24, 2026

Lung cancer development involves transformation of normal cells and remodeling of the tumor microenvironment, including the extracellular matrix (ECM). The study examines how therapy-related changes in gene expression of MMP2, MMP9, and the tissue inhibitor TIMP1 occur in the blood of NSCLC patients one year after surgical resection, and how expression differs between tumor and non-cancerous tissue. Blood tests showed no expression differences during therapy, whereas cancerous tissue showed higher MMP2 and MMP9 with unchanged TIMP1, and higher expression of each investigated gene correlated with shorter survival.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Study focus and molecular background

Abstract Findings

Blood vs. tumor tissue gene expression

Prognostic links to survival

biomedicines Article Correlation of TIMP1-MMP2/MMP9 Gene Expression Axis Changes with Treatment Efﬁcacy and Survival of NSCLC Patients Jacek Pietrzak 1, Agnieszka Wosiak 1, *, Dagmara Szmajda-Krygier 1, Rafał ´Swiechowski 1, Mariusz Łochowski 2, Milena Pa˛zik 1 and Ewa Balcerczak 1 Citation: Pietrzak, J.; Wosiak, A.; Szmajda-Krygier, D.; ´Swiechowski, R.; Łochowski, M.; Pa˛zik, M.; Balcerczak, E. Correlation of TIMP1-MMP2/MMP9 Gene Expression Axis Changes with Treatment Efﬁcacy and Survival of NSCLC Patients. Biomedicines 2023, 11, 1777. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biomedicines11071777 Academic Editor: Eric Huet Received: 12 May 2023 Revised: 16 June 2023 Accepted: 17 June 2023 Published: 21 June 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Laboratory of Molecular Diagnostics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, BRaIN Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland 2 Department of Thoracic Surgery, Copernicus Memorial Hospital, Medical University of Lodz, Pabianicka 62, 93-513 Lodz, Poland * Correspondence: [agnieszka.wosiak@umed.lodz.pl](agnieszka.wosiak@umed.lodz.pl) Abstract: In the course of lung cancer, normal cells are transformed into cancerous ones, and changes occur in the microenvironment, including the extracellular matrix (ECM), which is not only a scaffold for cells, but also a reservoir of cytokines, chemokines and growth factors. Metalloproteinases (MMPs) are among the elements that enable ECM remodeling. The publication focuses on the problem of changes in the gene expression of MMP2, MMP9 and tissue inhibitor of metalloproteinases (TIMP1) in the blood of NSCLC patients during therapy (one year after surgical resection of the tumor) . The paper also analyzes differences in the expression of the studied genes in the tumor tissue, as well as data collected in publicly available databases. The results of blood tests showed no differences in the expression of the tested genes during therapy; however, changes were observed in cancerous tissue, which was characterized by higher expression of MMP2 and MMP9, compared to non-cancerous tissue, and unchanged expression of TIMP1 . Nevertheless, higher expression of each of the studied genes was associated with shorter patient survival. Interestingly, it was not only the increased expression of metalloproteinase genes, but also the increased expression of the metalloproteinase inhibitor (TIMP1) that was unfavorable for patients. Keywords: lung cancer; NSCLC; metalloproteinases; tissue inhibitors of metalloproteinases; lung cancer treatment; NSCLC survival 1. Introduction In 2020, more than 2.2 million people worldwide were diagnosed with lung cancer, which was the second most common type of cancer in the population. However, this cancer was characterized by the highest death rate [1] . Most lung cancer cases are mainly related to environmental factors, with smoking considered as crucial. In highly developed countries, the number of cases is decreasing due to lifestyle changes, but in lower-income countries, an increasing trend has been observed. However, lung cancer is not diagnosed in people exposed to tobacco smoke only [2] . The most frequent type is non-small-cell lung cancer (NSCLC), occurring in about 85% of patients. There are two most common histological subtypes observed, i.e., adenocarcinoma and squamous cell carcinoma [3] . A signiﬁcant percentage of patients with diagnosed lung cancer present mutations in K-ras and the EGFR, ALK, BRAF, MEK, MET and TP53 oncogenes [4] . Their status is a marker fo

FAQs

Which genes were analyzed in NSCLC patients during therapy?

The study focused on MMP2, MMP9, and TIMP1 gene expression changes during treatment.

How did gene expression differ between blood and tumor tissue?

Blood tests showed no differences in expression during therapy, but tumor tissue exhibited higher MMP2 and MMP9 compared with non-cancerous tissue, with TIMP1 remaining unchanged.

What was the relationship between gene expression levels and patient survival?

Higher expression of each studied gene (including TIMP1) was associated with shorter patient survival.

Sep 24, 2026

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