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Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome.

ABSTRACT: Previously, we reported that proteomic fingerprints were present in sera of patients with severe acute respiratory syndrome (SARS), and could separate patients into subgroups with different prognoses. In the present study, we examined the prognostic values of the SARS-associated proteomic features by biostatistical analysis, and deciphered the identities of those with prognostic values. Data of 20 SARS-associated serum proteomic features and ten serological variables from 38 SARS adult patients before treatment were subjected to multivariate logistic regression. Proteomic features of m/z 6634, m/z 7769, m/z 8635, and m/z 8865 were identified as independent prognostic markers. After purification by cation-exchange chromatography and gel electrophoresis, proteomic features of m/z 7769 and m/z 8865 were found to be platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) by tandem mass spectrometry, respectively. The associations of decreased serum PF4 and increased serum beta-TG levels with poor prognosis were confirmed by Western blot. Previous studies suggest that PF4 and beta-TG are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) in a negative and positive way, respectively. Our results suggest that PF4 and beta-TG may also play similar roles in the development of ARDS in SARS patients.

SUBMITTER: Poon TC

PROVIDER: S-EPMC7163558 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome.

Poon Terence C W TC Pang Ronald T K RT Chan K C Allen KC Lee Nelson L S NL Chiu Rossa W K RW Tong Yu-Kwan YK Chim Stephen S C SS Ngai Sai M SM Sung Joseph J Y JJ Lo Y M Dennis YM

Electrophoresis 20120701 12

Previously, we reported that proteomic fingerprints were present in sera of patients with severe acute respiratory syndrome (SARS), and could separate patients into subgroups with different prognoses. In the present study, we examined the prognostic values of the SARS-associated proteomic features by biostatistical analysis, and deciphered the identities of those with prognostic values. Data of 20 SARS-associated serum proteomic features and ten serological variables from 38 SARS adult patients ...[more]

PMID: 22740477

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Project description:The present study aimed to discover potential biomarkers for predicting the prognosis of acute respiratory distress syndrome (ARDS) in conjunction with lung ultrasound (LUS). Blood samples from 112 ARDS patients were collected to compare their partial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2), positive end-expiratory pressure (PEEP), lactic acid, sequential organ failure assessment (SOFA) score, clinical pulmonary infection score (CPIS) and APACHE II score. Kaplan-Meier plots and the log-rank test were performed to analyse the association between the platelet-activating factor acetylhydrolase (PAFAH) G994T polymorphism and the outcome of ARDS regarding mortality. A negative correlation between the LUS score and PaO2/FiO2, PEEP and lactic acid, as well as with the SOFA, CPIS and APACHE II score was confirmed with correlation coefficients of -0.493, -0.548, -0.642, -0.598, -0.566 and -0.567, respectively (all P<0.05). The activity of PAFAH and high-density lipoprotein-PAFAH in the serum collected from subjects of the GG genotype was similar to that in subjects of the GT genotype, but the low-density lipoprotein-PAFAH activity in the serum collected from GG subjects was significantly higher than that in GT subjects. An evident reduction in the PEEP, level of lactic acid, as well as the SOFA, CPIS and APACHE II score was observed in GG subjects, accompanied by a significantly increased PaO2/FiO2. Kaplan-Meier analysis indicated that subjects with a high LUS score had a significantly higher survival rate than those with a low LUS score, and the mortality risk for GG subjects was significantly lower than that for GT subjects. Finally, among all groups (genotype and LUS groups), GG subjects with a high LUS score had the lowest mortality risk, whereas GT subjects with a low LUS score had the highest mortality risk. In addition, the survival rate of GT subjects with a high LUS score was higher than that of GG subjects with a low LUS score. In conclusion, the combination of the LUS score and the G994T polymorphism in exon 9 of the PAFAH gene may be used as a potential prognostic marker for ARDS.

Project description:BackgroundAcute respiratory distress syndrome (ARDS) is heterogeneous. As an indication of the heterogeneity of ARDS, there are patients whose syndrome improves rapidly (i.e., within 24 hours), others whose hypoxemia improves gradually and still others whose severe hypoxemia persists for several days. The latter group of patients with persistent severe ARDS poses challenges to clinicians. We attempted to assess the baseline characteristics and outcomes of persistent severe ARDS and to identify which variables are useful to predict it.MethodsA secondary analysis of patient-level data from the ALTA, EDEN and SAILS ARDSNet clinical trials was conducted. We defined persistent severe ARDS as a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) of equal to or less than 100 mmHg on the second study day following enrollment. Regularized logistic regression with an L1 penalty [Least Absolute Shrinkage and Selection Operator (LASSO)] techniques were used to identify predictive variables of persistent severe ARDS.ResultsOf the 1531 individuals with ARDS alive on the second study day after enrollment, 232 (15%) had persistent severe ARDS. Of the latter, 100 (43%) individuals had mild or moderate hypoxemia at baseline. Usage of vasopressors was greater [144/232 (62%) versus 623/1299 (48%); p<0.001] and baseline severity of illness was higher in patients with versus without persistent severe ARDS. Mortality at 60 days [95/232 (41%) versus 233/1299 (18%); p<0.001] was higher, and ventilator-free (p<0.001), intensive care unit-free [0 (0-14) versus 19 (7-23); p<0.001] and non-pulmonary organ failure-free [3 (0-21) versus 20 (1-26); p<0.001] days were fewer in patients with versus without persistent severe ARDS. PaO2:FiO2, FiO2, hepatic failure and positive end-expiratory pressure at enrollment were useful predictive variables.ConclusionsPatients with persistent severe ARDS have distinct baseline characteristics and poor prognosis. Identifying such patients at enrollment may be useful for the prognostic enrichment of trials.

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Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome.

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Proteomic analysis reveals platelet factor 4 and beta-thromboglobulin as prognostic markers in severe acute respiratory syndrome.

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