Dataset Information

Relevance of matrix metalloproteases in non-small cell lung cancer diagnosis.

ABSTRACT: The need for novel biomarkers that could aid in non-small cell lung cancer (NSCLC) detection, together with the relevance of Matrix Metalloproteases (MMPs) -1, -2, -7, -9 and -10 in lung tumorigenesis, prompted us to assess the diagnostic usefulness of these MMPs and the Tissue Inhibitor of Metalloproteinase (TIMP) -1 in NSCLC patients.Markers were evaluated in an initial study cohort (19 NSCLC cases and 19 healthy controls). Those that better performed were analyzed in a larger sample including patients with benign lung diseases. Serum MMPs and TIMP-1 were determined by multiplexed immunoassays. Logistic regression was employed for multivariate analysis of biomarker combinations.MMPs and TIMP-1 were elevated in the serum of NSCLC patients compared to healthy controls. MMP-1, -7 and -9 performed at best and were further evaluated in the sample including benign pathologies, corroborating the superiority of MMP-9 in NSCLC discrimination, also at early-stage NSCLC. The optimal diagnostic value was obtained with the model including MMP-9, gender, age and smoking history, that demonstrated an AUC of 0.787, 85.54% sensitivity and 64.89% specificity.Our results suggest that MMP-9 is a potential biomarker for NSCLC diagnosis and its combined measurement with other biomarkers could improve NSCLC detection.

SUBMITTER: Blanco-Prieto S

PROVIDER: S-EPMC5718060 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Relevance of matrix metalloproteases in non-small cell lung cancer diagnosis.

Blanco-Prieto Sonia S Barcia-Castro Leticia L Páez de la Cadena María M Rodríguez-Berrocal Francisco Javier FJ Vázquez-Iglesias Lorena L Botana-Rial María Isabel MI Fernández-Villar Alberto A De Chiara Loretta L

BMC cancer 20171205 1

<h4>Background</h4>The need for novel biomarkers that could aid in non-small cell lung cancer (NSCLC) detection, together with the relevance of Matrix Metalloproteases (MMPs) -1, -2, -7, -9 and -10 in lung tumorigenesis, prompted us to assess the diagnostic usefulness of these MMPs and the Tissue Inhibitor of Metalloproteinase (TIMP) -1 in NSCLC patients.<h4>Methods</h4>Markers were evaluated in an initial study cohort (19 NSCLC cases and 19 healthy controls). Those that better performed were an ...[more]

PMID: 29207990

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Project description:Interactions between cancer cells and the surrounding microenvironment are crucial determinants of cancer progression. During this process, bi-directional communication among tumor cells and cancer associated fibroblasts (CAF) regulate extracellular matrix (ECM) deposition and remodeling. As a result of this dynamic process, soluble ECM proteins can be released into the bloodstream and may represent novel circulating biomarkers useful for cancer diagnosis. The aim of the present study was to measure the levels of three circulating ECM related proteins (COL11A1, COL10A1 and SPARC) in plasma samples of lung cancer patients and in healthy heavy-smokers controls and test whether such measurements have diagnostic or prognostic value.Gene expression profiling of lung fibroblasts isolated from paired normal and cancer tissue of NSCLC patients was performed by gene expression microarrays. The prioritization of the candidates for the study of circulating proteins in plasma was based on the most differentially expressed genes in cancer associated fibroblasts. Soluble ECM proteins were assessed by western blot in the conditioned medium of lung fibroblasts and by ELISA assays in plasma samples.Plasma samples from lung cancer patients and healthy heavy-smokers controls were tested for levels of COL11A1 and COL10A1 (n?=?57 each) and SPARC (n?=?90 each). Higher plasma levels of COL10A1 were detected in patients (p???0.001), a difference that was driven specifically by females (p?<?0.001). No difference in COL11A1 levels between patients and controls was found. SPARC levels were also higher in plasma patients than controls (p?<?0.001) with good performance in discriminating the two groups (AUC?=?0.744). No significant association was observed between plasma proteins levels and clinicopathological features or survival.Soluble factors related to proficient tumor-stroma cross-talk are detectable in plasma of primary lung cancer patients and may represent a valuable complementary diagnostic tool to discriminate lung cancer patients from healthy heavy-smokers individuals as shown for the SPARC protein.

Dataset Information

Relevance of matrix metalloproteases in non-small cell lung cancer diagnosis.

Publications

Relevance of matrix metalloproteases in non-small cell lung cancer diagnosis.

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