Translational research : the journal of laboratory and clinical medicine
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Clinical Trial
The Within-Individual Reproducibility of the Disease Severity Index from the HepQuant SHUNT® Test of Liver Function and Physiology.
The HepQuant SHUNT test quantifies liver function and blood flow using systemic and portal clearances of cholate. The test can identify the risk of well-compensated patients to develop complications of cirrhosis. To confirm the reliability of a single HepQuant SHUNT test we defined its within-individual reproducibility. ⋯ The other test parameters had ICCs ranging from 0.74 (SHUNT) to 0.90 (STAT). In Bland-Altman analysis, the mean of differences between measurements of DSI was 0.13 with standard deviation 2.12. The excellent reproducibility of the HepQuant SHUNT test, particularly DSI, supports the use this minimally invasive, blood-based test as a reliable test of liver function and physiology.
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Once thought of as arising from "junk DNA," noncoding RNAs (ncRNAs) have emerged as key molecules in cellular processes and response to stress. From diseases such as cancer, coronary artery disease, and diabetes to the effects of ionizing radiation (IR), ncRNAs play important roles in disease progression and as biomarkers of damage. Noncoding RNAs regulate cellular processes by competitively binding DNA, mRNA, proteins, and other ncRNAs. ⋯ Furthermore, some studies have reported modulation of radiosensitivity by altering expression levels of these ncRNAs. This review discusses the roles of ncRNAs in the radiation response and evaluates prior research on ncRNAs as biomarkers of radiation damage. Future directions and applications of ncRNAs in radiation research are introduced, including the potential for a clinical ncRNA assay for assessing radiation damage and for the therapeutic use of RNA interference (RNAi).
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The gonadotropin-releasing hormone (GnRH) signaling pathway controls reproductive functions and cancer growth and progression. However, few studies investigated roles of genetic variants of GnRH pathway genes in survival of patients with non-small cell lung cancer (NSCLC). Therefore, we first evaluated associations between 22,528 single-nucleotide polymorphisms (SNPs) in 101 GnRH pathway genes and survival of 1185 NSCLC patients using a dataset from Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. ⋯ Further expression quantitative trail loci analysis showed a significant correlation between ITPR3 rs116454384 T allele and an increased mRNA expression level in both whole blood and normal lung tissue, and high ITPR3 mRNA expression levels in tumors were associated with a better survival of NSCLC patients. Because ITPR3 mutations were rare in tumors, ITPR3 rs116454384C>T likely had an effect on cancer progression by regulating the gene expression. Therefore, genetic variants of HBEGF rs4150236G>A and ITPR3 rs116454384C>T may be predictors for NSCLC survival, but HBEGF rs4150236G>A functional relevance remains to be determined.
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Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). ⋯ Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80-0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up.
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Observational Study
Circulating Chaperones in Patients with Aortic Valve Stenosis Undergoing TAVR: Impact of Concomitant Chronic Kidney Disease.
Chronic kidney disease (CKD) is a frequent comorbidity of aortic valve stenosis (AVS). Circulating chaperones have emerged as both effectors and prognostic markers for various diseases. We investigated the role of circulating chaperones in patients with severe AVS undergoing transcatheter aortic valve replacement (TAVR). ⋯ In patients with CKD, elevated HSP27 was identified as a protective marker (1-year mortality: 9.6% vs 31.4%, log-rank P = 0.0166). Using cut-off values for GRP78 and HSP27 we were able to stratify patients with CKD undergoing TAVR into 4 groups with distinct mortality rates (50% vs 22.2% vs 24% vs 7.9%, log-rank P = 0.0170). GRP78 is an overall predictor of mortality after TAVR, while the combination of GRP78 and HSP27 helps to predict mortality in patients with CKD receiving TAVR.