The online version of this article (https://doi.org/10.1186/s12885-018-4772-0) contains supplementary material, which is available to authorized users.
Francesca Andriani and Elena Landoni contributed equally to this work.
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.
Additional file 1: Table S1. Quantile regression multivariable analysis of association between COL11A1 and COL10A1 levels and the characteristics of 57 lung cancer patients and 57 healthy controls. (DOCX 15 kb)12885_2018_4772_MOESM1_ESM.docx
Additional file 2: Figure S1. COL11A and COL10A levels are not associated with overall survival. Kaplan Meier overall survival (OS) curves for COL11A1 and COL10A1 levels divided into three categories (≤1st tertile, 1st-2nd tertile, >2nd tertile) on the entire case series p = log-rank test p-value. (PPTX 51 kb)12885_2018_4772_MOESM2_ESM.pptx
Additional file 3: Table S2. Sensitivity and specificity data for SPARC cutoffs. (DOCX 18 kb)12885_2018_4772_MOESM3_ESM.docx
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- Diagnostic role of circulating extracellular matrix-related proteins in non-small cell lung cancer
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Mario Paolo Colombo
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