Levels and prognostic impact of circulating markers of inflammation, endothelial activation and extracellular matrix remodelling in patients with lung cancer and chronic obstructive pulmonary disease

Abstract

BackgroundThe development of both chronic obstructive pulmonary disease (COPD) and lung cancer (LC) is influenced by smoking related chronic pulmonary inflammation caused by an excessive innate immune response to smoke exposure. In addition, the smoking induced formation of covalent bonds between the carcinogens and DNA and the accumulation of permanent somatic mutations in critical genes are important in the carcinogenic processes, and can also induce inflammatory responses.How chronic inflammation is mirrored by serum markers in COPD and LC and if these markers reflect prognosis in patients with LC is, however, largely unknown.MethodsSerum levels of 18 markers reflecting inflammation, endothelial activation and extracellular matrix remodelling were analysed in 207 patients with non-small lung carcinoma (NSCLC) before surgery and 42 COPD patients. 56% of the LC patients also suffered from COPD. The serum samples were analysed by enzyme immunoassays.ResultsSerum levels of OPG, PTX3, AXL, ALCAM, sCD163, CD147, CatS and DLL1 were significantly higher in patients with COPD as compared to patients with LC. High sTNFR1 levels were associated with improved progression free survival (PFS) and overall survival (OS) in LC patients with (PFS hazard ratio (HR) 0.49, OS HR 0.33) and without COPD (OS HR 0.30). High levels of OPG were associated with improved PFS (HR 0.17) and OS (HR 0.14) for LC with COPD. CRP was significantly associated with overall survival regardless of COPD status.ConclusionSeveral markers reflecting inflammation, endothelial activation and extracellular matrix remodelling are elevated in serum from patients with COPD compared to LC patients. Presence of COPD might influence the levels of circulating biomarkers. Some of these markers are also associated with prognosis.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4659-0) contains supplementary material, which is available to authorized users.

CD147 increases mucus secretion induced by cigarette smoke in COPD

“…What is more, previous studies have demonstrated the role of CD147 in regulating inflammatory responses in a variety of diseases, including lung inflammation [18–20]. Berg et al found that serum levels of CD147 were high in COPD patients [21]. Since MMP9 and p38 MAPK are indispensable signaling molecules in the regulation of MUC5AC secretion, we hypothesize that CD147 may take part in MUC5AC production in COPD through these signaling molecules.…”

Nidogen 1‐Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1

“…In contrast, a higher level of sTNFR1 is associated with better survival in lung cancer patients with and without chronic obstructive pulmonary disease. [51] In addition to its role in cancer, sTNFR1 is strongly associated with other diseases, such as cardiovascular mortality [52] and nonrelapse mortality after hematopoietic cell transplantation. [53] EVs are regarded as a molecular signature of the parental cells and provide insight about the origin and functions of the parental cells.…”

The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer

“…In addition, ROC analysis indicated that PTX3 could discriminate between cancer patients and heavy smokers at high risk for lung cancer (127). Similarly, high PTX3 levels were correlated with worse progression-free survival in patients with lung cancer and chronic obstructive pulmonary disease (132), and with overall survival and disease-free survival in small-cell lung carcinoma (SCLC) (133). A recent study on 1358 individuals at high risk for lung cancer demonstrated that PTX3 levels were not predictive of pathology occurrence (128).…”