Plasma and serum are rich sources of information regarding an individual's health state, and protein tests inform medical decision making. Despite major investments, few new biomarkers have reached the clinic. Mass spectrometry (MS)‐based proteomics now allows highly specific and quantitative readout of the plasma proteome. Here, we employ Plasma Proteome Profiling to define quality marker panels to assess plasma samples and the likelihood that suggested biomarkers are instead artifacts related to sample handling and processing. We acquire deep reference proteomes of erythrocytes, platelets, plasma, and whole blood of 20 individuals (> 6,000 proteins), and compare serum and plasma proteomes. Based on spike‐in experiments, we determine sample quality‐associated proteins, many of which have been reported as biomarker candidates as revealed by a comprehensive literature survey. We provide sample preparation guidelines and an online resource ( http://www.plasmaproteomeprofiling.org) to assess overall sample‐related bias in clinical studies and to prevent costly miss‐assignment of biomarker candidates.
Cervical cancer lacks reliable prognostic factors for both progression and chemotherapeutic responsiveness. The expression of the LDOC1 tumor suppressor candidate was therefore investigated. In four of six cervical cancer cell lines tested, expression of LDOC1 was silenced. Downregulation of LDOC1 could also be shown in biopsies of cervical cancer specimens. PCR-based promoter methylation analysis revealed a significant association between promoter methylation and the loss of LDOC1 expression, which could be reverted by DNA methyltransferase inhibitors. This indicates that silencing of LDOC1 is a frequent event in cervical cancer and may be of interest as a molecular marker in cervical cancer.
The tumor suppressor gene LDOC1 in ovarian cancer cell lines is downregulated by promoter methylation and thus may serve as an early biomarker. Further investigation will show if detection of methylated LDOC1 in peripheral blood has both adequate sensitivity and specificity for a timely non-invasive detection of ovarian cancer.
<b><i>Introduction:</i></b> A proportion of patients with drug-induced liver injury (DILI) present with autoantibodies, which has led to the current concept of autoimmune-like DILI. However, no standardized definition exists and the clinical relevance has not been studied in detail yet. <b><i>Methods:</i></b> 143 patients with DILI enrolled in a prospective study were analyzed. DILI diagnosis was based on the monocyte-derived hepatocyte-like cell test and supported by Roussel Uclaf Causality Assessment Method (RUCAM) and expert adjudication. Testing for antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) was performed using immunofluorescence. ANA titers ≥1:100 were considered positive and ≥1:400 clinically relevant; AMA positivity was considered at titers ≥1:100. <b><i>Results:</i></b> 67% exhibited ANA ≥1:100 and 29% ANA ≥1:400; 10% were AMA positive. There was no significant correlation between the ANA titers and the causative drug, while AMA positive patients had taken nonsteroidal anti-inflammatory drugs more frequently. No difference was seen regarding clinical characteristics or laboratory parameters in patients with ANA ≥1:400, while patients with positive AMA presented with higher aminotransferases, bilirubin, and international normalized ratio. Significantly higher proportions of patients with ANA ≥1:400 or AMA positivity exhibited elevated immunoglobulin G levels. AMA positivity but not elevated ANA titers correlated with a higher proportion of Hy’s law positivity. <b><i>Conclusion:</i></b> A closer look in a causality proven DILI cohort provided no evidence that presence of ANA titers is specific for DILI by a certain medication. AMA rather than ANA positivity was related to a more pronounced liver injury.
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