Journal of biomarkers最新文献

Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30-40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis.

Melanoma is the most malignant type of skin cancer. Early detection of melanoma is thus critical for patient prognosis and survival. At present, examination by a skilled dermatologist followed by biopsy of suspicious lesions is the diagnostic gold standard. The aim of the present study was to examine an alternative and noninvasive method for the diagnosis of melanoma at an early stage. We identified and compared the volatile organic compounds (VOCs) in mouse urine and feces, before and after a subcutaneous injection of B16 melanoma cells. We identified a total of 16 VOCs in urine and 13 VOCs in feces that could serve as potential biomarkers. Statistical analysis significantly discriminated between the cancer and control groups. These results should be validated in a larger-scale animal study, after which a study could be designed in patients to develop a melanoma biomarker.

An early diagnosis and appropriate treatment are crucial in reducing mortality among people suffering from cancer. There is a lack of characteristic early clinical symptoms in most forms of cancer, which highlights the importance of investigating new methods for its early detection. One of the most promising methods is the analysis of volatile organic compounds (VOCs). VOCs are a diverse group of carbon-based chemicals that are present in exhaled breath and biofluids and may be collected from the headspace of these matrices. Different patterns of VOCs have been correlated with various diseases, cancer among them. Studies have also shown that cancer cells in vitro produce or consume specific VOCs that can serve as potential biomarkers that differentiate them from noncancerous cells. This review identifies the current challenges in the investigation of VOCs as potential cancer biomarkers, by the critical evaluation of available matrices for the in vivo and in vitro approaches in this field and by comparison of the main extraction and detection techniques that have been applied to date in this area of study. It also summarises complementary in vivo, ex vivo, and in vitro studies conducted to date in order to try to identify volatile biomarkers of cancer.

Colorectal cancer (CRC) is the third common carcinoma with a high rate of mortality worldwide and several studies have investigated some molecular and clinicopathological markers for diagnosis and prognosis of its malignant phenotypes. The aim of this study is to evaluate expression frequency of PAGE4, SCP-1, and SPANXA/D cancer testis antigen (CTA) genes as well as some clinical risk markers to predict liver metastasis of colorectal cancer patients. The expression frequency of PAGE4, SCP-1, and SPANXA/D cancer/testis antigen (CTA) genes was obtained using reverse transcription polymerase chain reaction (RT-PCR) assay in 90 colorectal tumor samples including both negative and positive liver metastasis tumors. Statistical analysis was performed to assess the association of three studied genes and clinical risk factors with CRC liver metastasis. The frequency of PAGE4 and SCP-1 genes expression was significantly higher in the primary tumours with liver metastasis when statistically compared with primary tumors with no liver metastasis (P < 0.05). Among all clinical risk factors studied, the lymph node metastasis and the depth of invasion were statistically correlated with liver metastasis of CRC patients. In addition, using multiple logistic regression, we constructed a model based on PAGE4 and lymph node metastasis to predict liver metastasis of CRC.

Prostate cancer (PCA) is a major health concern in current times. Ever since prostate specific antigen (PSA) was introduced in clinical practice almost three decades ago, the diagnosis and management of PCA have been revolutionized. With time, concerns arose as to the inherent shortcomings of this biomarker and alternatives were actively sought. Over the past decade new PCA biomarkers have been identified in tissue, blood, urine, and other body fluids that offer improved specificity and supplement our knowledge of disease progression. This review focuses on superiority of circulating biomarkers over tissue biomarkers due to the advantages of being more readily accessible, minimally invasive (blood) or noninvasive (urine), accessible for sampling on regular intervals, and easily utilized for follow-up after surgery or other treatment modalities. Some of the circulating biomarkers like PCA3, IL-6, and TMPRSS2-ERG are now detectable by commercially available kits while others like microRNAs (miR-21, -221, -141) and exosomes hold potential to become available as multiplexed assays. In this paper, we will review some of these potential candidate circulating biomarkers that either individually or in combination, once validated with large-scale trials, may eventually get utilized clinically for improved diagnosis, risk stratification, and treatment.

The present study aimed to determine the day to day variability and reliability of several blood oxidative stress markers at rest in a healthy young cohort over a four-week period. Twelve apparently healthy resistance trained males (24.6 ± 3.0 yrs) were tested over 7 visits within 4 weeks with at least 72 hrs between visits at the same time of day. Subjects rested 30 minutes prior to blood being obtained by vacutainer. Results. The highest IntraClass correlations (ICC's) were obtained for protein carbonyls (PC) and oxygen radical absorbance capacity (ORAC) (PC = 0.785 and ORAC = 0.780). Cronbach's α reliability score for PC was 0.967 and for ORAC was 0.961. The ICC's for GSH, GSSG, and the GSSG/TGH ratio ICC were 0.600, 0.573, and 0.570, respectively, with Cronbach's α being 0.913, 0.904, and 0.903, respectively. Xanthine oxidase ICC was 0.163 and Cronbach's α was 0.538. Conclusions. PC and ORAC demonstrated good to excellent reliability while glutathione factors had poor to excellent reliability. Xanthine oxidase showed poor reliability and high variability. These results suggest that the PC and ORAC markers were the most stable and reliable oxidative stress markers in blood and that daily changes across visits should be considered when interpreting resting blood oxidative stress markers.

Granulomatosis with polyangiitis (GPA) is a small blood vessel vasculitic disorder with a high mortality rate if undiagnosed or treated inadequately. Disease relapse is a key feature of this disease and early identification of relapse episodes is very important in limiting end-organ damage. The advent of indirect immunofluorescence to detect antineutrophil cytoplasmic antibody (ANCA) with specific reactivity against the enzyme proteinase-3 (PR3) has been very useful in the diagnosis of GPA but is less helpful in predicting relapse. Indeed, up to date no satisfactory biomarker has been identified that can reliably predict relapse. This study assessed the probability of the occurrence of a relapse when a change was noted in a range of commonly used laboratory tests. These tests included levels of C-reactive protein (CRP), anti-PR3 antibodies, ANCA titre, and the neutrophil count. A group of 30 GPA patients with a total of 66 relapse episodes was investigated and a novel clinical yield score was devised. When a combined rise in CRP, anti-PR3 antibodies, and neutrophil count was observed in the 6-month period before a relapse event, 59% of patient relapses could be predicted. Monitoring changes in this set of parameters helps identify disease relapse.

A prospective case control study was undertaken to evaluate the diagnostic performance of serum heart-type fatty acid binding protein (HFABP) in comparison to cardiac TnT and TnI in 33 patients admitted with chest pain, diagnosed as NSTE-ACS (non ST elevation acute coronary syndrome) and 22 healthy controls. Area under the receiver operating curve (AUC) was highest for H-FABP (AUC 0.79; 95% CI 0.66-0.89) versus cTnI (AUC 0.73; 95% CI 0.59-0.84) and cTnT (AUC 0.71; 95% CI 0.57-0.83). The H-FABP level above 6.5 ng/mL showed 56.7% (CI 37.4-74.5) sensitivity, 0.5 (95% CI 0.3-0.7) negative likelihood ratio (-LR), 100% (CI 84.6-100.0) specificity, and 100% (CI 79.4-100.0) positive predictive value (PPV), 62.9% (CI 44.9-78.5) negative predictive value (NPV). cTnI level above 0.009 μg/L had 40% (CI 22.7-59.4) sensitivity, 0.6 (95% CI 0.4-0.8) -LR, 100% (CI 84.6-100.0) specificity, 100% (CI 73.5-100.0) PPV, and 55% (CI 38.5-70.7) NPV. cTnT showed 46.7% (CI 28.3-65.7) sensitivity, 0.5 (95% CI 0.4-0.7) -LR, 100% (CI 84.6-100.0) specificity, 100% (CI 76.8-100.0) PPV, and 57.9% (CI 40.8-73.7) NPV at level above 9 μg/L. +LR were 12.5 (95% CI 1.8-86.8), 1.7 (95% CI 1.0-3.0), and 1.2 (95% CI 0.8-1.9) for H-FABP, cTnI, and cTnT respectively. In conclusion measurement of H-FABP is a valuable tool in the early diagnosis of patients with chest pain (6-8 hrs) and seems to be a preferred biomarker in the differential diagnosis of NSTE-ACS. More studies are needed to determine whether serum H-FABP further improves diagnostic performance.

Transcriptional silencing, as a result of aberrant promoter hypermethylation, is a common mechanism through which genes in cancer cells become inactive. Functional epigenetic screens using demethylating agents to reexpress transcriptional silenced genes may identify such inactivated genes for needing further evaluation. We aimed to identify genes so far not known to be inactivated by promoter hypermethylation in prostate cancer. DU-145 and LNCaP cells were treated with the DNMT inhibitor zebularine. Expression changes of total RNA from treated and untreated cells were compared using an RNA expression microarray. Genes upregulated more than 2-fold were evaluated by RT-qPCR in 50 cases of paired normal and tumor tissues of prostate cancer patients. SARS was found to be downregulated in prostate cancer in 42/50 cases (84%). In addition, GADD45A and SPRY4 showed a remarkable diminished expression (88% and 74%, resp.). The gold standard for promoter hypermethylation-inactivated genes in prostate cancer (GSTP1) was repressed in 90% of our patient samples. ROC analyses reported statistically significant AUC curves in SARS, GADD45A, and GSTP1 and positive Spearman correlations were found between these genes. SARS was discovered to be a novel gene that is repressed in prostate cancer and could therefore be recommended for its involvement in prostate carcinogenesis.

Objective. Increasing prevalence of asthma has been attributed to changes in lifestyle and environmental exposures. We conducted a case-control study to investigate the relationship between serum micronutrients and asthma in rural school children in Nigeria. Methods. We administered questionnaires to 1,562 children to identify children with asthma. Serum concentration levels of 12 micronutrients were determined in asthma cases (N = 37) and controls (N = 30). Allergy skin prick test and spirometry were also performed. Results. Plasma levels of the following micronutrients were significantly different between cases and controls: calcium (7.48 ± 2.16 versus 8.29 ± 1.62 mg/dL; P = 0.04), manganese (44.1 ± 11.5 versus 49.3 ± 7.9 mg/L; P = 0.01), selenium (76.1 ± 14.9 versus 63.3 ± 26.8 μg/L; P = 0.02), and albumin (3.45 ± 0.90 versus 3.91 ± 0.99 g/dL; P = 0.04). Plasma concentrations of iron and selenium were positively correlated with lung function, r = 0.43 (P < 0.05 in each case) while manganese serum concentration was negatively correlated with asthma (r = -0.44; P < 0.05). Conclusions. Children with asthma had reduced levels of plasma manganese, calcium, and albumin but raised level of selenium. The protective or risk effects of these micronutrients on asthma warrant further investigation.