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Plasma and Cellular Forms of Fibronectin as Prognostic Markers in Sepsis.

ABSTRACT: Background:There is a pressing need for specific prognostic markers that could be used to monitor the severity of sepsis. The aims of our study were to investigate changes in the expression of different molecular forms of fibronectin in sepsis and to assess their relationship to the clinical severity and mortality of patients. Material and Methods. Forms of fibronectin: plasma (pFN), cellular (EDA-FN), FN-fibrin complexes, and fibronectin fragments were analyzed in 71 sepsis patients (survivors and nonsurvivors) and in the control by ELISA and immunoblotting. Results:The baseline pFN concentration of patients with sepsis was significantly lower than in the control (133.0?mg/L vs. 231.2?mg/L) (P < 0.001), and in nonsurvivors, it was lower than in survivors (106.0?mg/L vs. 152.8?mg/L) (P = 0.004). The baseline EDA-FN was significantly elevated in both sepsis groups (survivors: 6.7?mg/L; nonsurvivors: 9.4?mg/L) compared to the control (1.4?mg/L) (P < 0.001). It should be noted that among patients with more severe sepsis, the EDA-FN level was higher in nonsurvivors than in survivors. Furthermore, molecular FN-fibrin complexes as well as FN fragments occurred much more frequently in nonsurvivors than in survivors. Conclusion:The study showed that in sepsis, changes in plasmatic and cellular form of fibronectin were associated with the severity of sepsis and may be useful predictors of outcome.

SUBMITTER: Lemanska-Perek A

PROVIDER: S-EPMC7416265 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Plasma and Cellular Forms of Fibronectin as Prognostic Markers in Sepsis.

Lemańska-Perek Anna A Krzyżanowska-Gołąb Dorota D Skalec Tomasz T Adamik Barbara B

Mediators of inflammation 20200801

<h4>Background</h4>There is a pressing need for specific prognostic markers that could be used to monitor the severity of sepsis. The aims of our study were to investigate changes in the expression of different molecular forms of fibronectin in sepsis and to assess their relationship to the clinical severity and mortality of patients. <i>Material and Methods</i>. Forms of fibronectin: plasma (pFN), cellular (EDA-FN), FN-fibrin complexes, and fibronectin fragments were analyzed in 71 sepsis patie ...[more]

PMID: 32801997

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Project description:Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan-Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02-4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian-epithelial origin of the tumor.

Project description:BACKGROUND:Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular and immune function. NO is generated by nitric oxide synthases (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NOS. Increased inhibitor blood concentrations lead to reduce NO bioavailability. The aim of this study was to determine whether plasma concentrations of SDMA and ADMA are markers for sepsis survival. METHOD:This prospective, single center study involved 120 ICU patients with sepsis. Plasma SDMA and ADMA were measured on admission (day 1), day 3 and day 7 by mass spectrometry together with other laboratory markers. The sequential organ failure assessment (SOFA) score was used to evaluate sepsis severity. Survival was documented until day 28. Groups were compared using the Mann-Whitney U test, chi-squared test or non-parametric analysis of variance (ANOVA). Mortality was assessed using Kaplan-Meier curves and compared using the log-rank test. Specific risk groups were identified using a decision tree algorithm. RESULTS:Median plasma SDMA and ADMA levels were significantly higher in non-survivors than in survivors of sepsis: SDMA 1.14 vs. 0.82 ?mol/L (P?=?0.002) and ADMA 0.93 vs. 0.73 ?mol/L (P?=?0.016). ANOVA showed that increased plasma SDMA and ADMA concentrations were significantly associated with SOFA scores. The 28-day mortality was compared by chi-square test: for SDMA the mortality was 12% in the lower, 25% in the intermediate and 43% in the 75th percentile (P?=?0.018); for ADMA the mortality was 18-20% in the lower and intermediate but 48% in the 75th percentile (P?=?0.006). The highest mortality (61%) was found in patients with plasma SDMA >?1.34 together with ADMA levels >?0.97 ?mol/L. CONCLUSIONS:Increased plasma concentrations of SDMA and ADMA are associated with sepsis severity. Therefore, our findings suggest reduced NO bioavailability in non-survivors of sepsis. One may use individual SDMA and ADMA levels to identify patients at risk. In view of the pathophysiological role of NO we conclude that the vascular system and immune response are most severely affected when SDMA and ADMA levels are high.

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Plasma and Cellular Forms of Fibronectin as Prognostic Markers in Sepsis.

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Plasma and Cellular Forms of Fibronectin as Prognostic Markers in Sepsis.

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