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Hazardous environmental factors as well as occupational factors can lead to elevated incidence of diseases including tumors, and specific molecular biomarkers are needed to guide the diagnosis and treatment of diseases. In recent years, ubiquitin-specific protease 14 (USP14) has gradually attracted the attention of researchers. USP14 is widely expressed in various organs of human body and regulates the stability and degradation of important proteins in various signaling pathways. Studies have shown that its abnormal expression is highly correlated with tumors, neurodegenerative diseases, autophagy, immune response, and viral infections, and is involved in the regulation of various classic signaling pathways. It has been shown to play a key role in the development of various human diseases and can be used as a diagnostic and prognostic molecular biomarker and therapeutic target in the development of tumors. This paper reviewed the current status of research on the structure and regulation of USP14 and its function in physiological and pathological processes, with the aim of providing a reference for research on diseases or injuries caused by environmental and occupational factors.
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Routine pathological examination of unexplained sudden cardiac death (USCD) lacks significant morphological characteristics. In the field of forensic medicine, molecular biology methods have been used to find the cause of death by detecting genes and research related to the mechanism of sudden cardiac death has been carried out. From the molecular pathology point of view, the application of multiple levels of biomarkers to resolve the causes of USCD has already shown potential and provides an important path for forensic identification of USCD. This article reviews the latest research progress on USCD-related genes, RNA, proteins and USCD, and summarizes forensic application.
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Humans , Biomarkers , Death, Sudden, Cardiac/pathology , Forensic Medicine , Forensic Pathology , HeartABSTRACT
Objective To investigate the expression level of serum miR-193a-3p,miR-337-5p and miR-483-5p in esophageal squamous cell carcinoma (ESCC) patients and to explore their value for diagnosis and prognosis of ESCC.Methods Serum samples were collected from 63 ESCC patients before and after surgery in Nanjing General Hospital and Xuzhou Cancer Hospital between June 2013 and May 2014 and serum sanples of 63 age-and sex-matched healthy individuals acted as the normal controls.TaqMan Low Density Assay was used to detect the deregulated miRNA in ESCC patients and then quantitative real-time PCR was used to validate the upregulated miRNA miR-193a-3p,miR-337-5p and previously reported miR483-5p that was upregulated in oral squamous cell carcinoma (OSCC).Finally,the three miRNA were evaluated for their clinical value in the diagnosis and predicting prognosis of ESCC.Results Compared with normal controls,serum levels of miR193a-3p,miR-337-5p and miR-483-5p in ESCC patients were significantly up-regulated (0.459±0.339 vs 0.195±0.084,U =591;5.686±5.211 vs 2.476±0.808,U=605;32.545 ± 22.479 vs 19.509±10.601,U=1 037,respectively,all P＜ 0.0001) and their levels were significantly reduced after the surgical treatment (P＜0.05).The areas under the ROC curve of serum miR-193a-3p,miR-337-5p,miR-483-5p and miR-Panel were all larger than that of CEA.Univariate Kaplan-Meier analysis revealed that ESCC patients with low expression level of miR-483-5p in postoperative serum exhibited higher survival rate than those with high level(P=0.022).Conclusion Serum miR-193a-3p,miR-337-5p and miR-483-5p can be potential molecular biomarkers in the diagnosis and predicting prognosis of ESCC.
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Radiation biodosimetry is an important part of radiation medicine. Some new discoveries and progresses have been made in radiation biodosimetry studies in recent years. Cytogenetic method represented by chromosome aberration analysis as the golden standard of radiation biodosimeter is being transformed to automate analysis, and a number of international, regional and national laboratory networks of radiation biodosimetry are being established. As a widely acceptable molecular marker of DNA damage,γ-H2AX has made rapid progress in radiation dose estimation. Based on the expressions of protein and genes, further advancements have been made in the studies of metabolites and miRNAs. At the same time, with the development of proteomics technology, there are some breakthroughs in the study of using molecular expression profiling to evaluate radiation dose. The research progresses of radiation biodosimetry is reviewed in this paper.
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Radiation biodosimetry is an important part of radiation medicine. Some new discoveries and progresses have been made in radiation biodosimetry studies in recent years. Cytogenetic method represented by chromosome aberration analysis as the golden standard of radiation biodosimeter is being transformed to automate analysis, and a number of international, regional and national laboratory networks of radiation biodosimetry are being established. As a widely acceptable molecular marker of DNA damage,γ-H2AX has made rapid progress in radiation dose estimation. Based on the expressions of protein and genes, further advancements have been made in the studies of metabolites and miRNAs. At the same time, with the development of proteomics technology, there are some breakthroughs in the study of using molecular expression profiling to evaluate radiation dose. The research progresses of radiation biodosimetry is reviewed in this paper.
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Tumor recurrence is the main factor affecting the postoperative prognosis of hepatocellular carcinoma.The forecast of tumor recurrence by monitoring biomarker can effectively improve the prognosis of such disease.To improve the detection rate of early cancer recurrence can be achieved by detecting the level of the alpha-fetoprotein (AFP),Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3),des-γ-carboxyprothrombin (DCP),or combined detection.In recent years,the researches on the miRNA and Long Noncoding RNAs (LncRNA),which are key regulators in the upstream of signal pathways,could provide a new way for HCC recurrence monitoring.The combined detection of biomarkers in different control levels,maybe is the effective measure to improve the tumor recurrence detection rate,and is also the focus of the further research.
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Objective To determine the levels of miR-193a-3p in serum from patients with renal clear cell carcinoma,and eval-uate the potential of miR-193a-3p asa molecular biomarker of renal clear cell carcinoma.Methods Serum samples were taken from 107 untreated hospitalized patients with renal clear cell carcinoma (TNM Ⅰ grade 76 cases,Ⅱ grade 16 cases,Ⅲ grade 2 cases,Ⅳ grade 8 cases and unknown 5 cases)in Nanjing General Hospital from 2010 to 2014 year and 107 age-and gender-matched healthy individuals to determine the level of miR-193a-3p by quantitative reverse-transcription PCR (qRT-PCR). The early diagnostic value of miR-193a-3p for renal clear cell carcinoma was assessed by ROC curve.Results qRT-PCR confirmed that serum miR-193a-3p expression levels was significantly elevated in cancer than in normal controls (3.294± 1.526 vs 1.944±0.600,P =0.000).TNM Ⅰ grade (3.411±1.676 vs 1.944±0.600,P =0.000),Ⅱ grade (2.926±0.927 vs 1.944±0.600,P =0.001),Ⅳ grade(2.926±0.894 vs 1.944±0.600,P =0.000)is significantly higher than that in con-trol group.The area under the ROC curve (AUC)of miR-193a-3p was 0.820 (95% CI,0.756 ~ 0.883),demonstratinga high sensitivity (80.3%)and specificity (93.5%)for the early diagnosis of renal clear cell carcinoma.Conclusion MiR-193a-3p content was significantly elevated in serum from renal clear cell carcinoma and has a high accuracy in diagnosing ear-ly cancer,which holds potential as molecular biomarker for renal clear cell carcinoma.
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Recently, biomarkers in medicine have gained comprehensive scientific and clinical interest. Biomarker or biological marker defined as alteration in the constituents of tissues or body fluids provide a powerful approach to understanding the spectrum of chronic diseases with application in at least 5 areas like screening, diagnosis, prognostication, prediction of disease recurrence and therapeutic monitoring. Therefore, biomarkers are biological indicators of diseases that can be measured either in vivo by biomedical imaging or in vitro by laboratory methods. Many kinds of biomarkers are available in the field of medical science with lots of positive as well as negative effect. These markers can also reflect the entire spectrum of disease from the earliest manifestations to the terminal stages and will become one of the major driving forces of pharmaceutical research and drug development in the coming years. Generally, a biomarker is potentially useful along the whole spectrum of the disease process- before diagnosis; for screening and risk assessment, during diagnosis; for staging, grading and selecting the initial therapy and during treatment for monitoring therapy, selecting additional therapy or monitoring recurrent diseases. This brief review describes the types and major uses of biomarkers in clinical investigation.
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PURPOSE: To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. MATERIALS AND METHODS: Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and beta-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. RESULTS: At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and beta-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. CONCLUSION: There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and beta-catenin. Future research is needed on a larger data set or with other molecular biomarkers.
Subject(s)
Humans , Antibodies , beta Catenin , Bile Ducts, Extrahepatic , Biomarkers , Chemoradiotherapy , Cytoplasm , Follow-Up Studies , Immunohistochemistry , Matrix Metalloproteinase 9 , Medical Records , Proto-Oncogene Proteins c-akt , Retrospective StudiesABSTRACT
Objective:To sieve molecular biomarkers associated with heart failure derived from arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods:The comparative gene microarray analysis using individual left ventricular myocardial samples from 5 patients with heart failure resulting from ARVC undergoing transplantation and 5 matched samples from normal adult heart were performed.The accuracy rate of the differentially expressed genes obtained by gene microarray was further verified by quantitative real time RT-PCR.Results:83 genes (from a total of 35000) that were differentially expressed in diseased hearts versus normal hearts were identified.Among them thirty-seven genes were up-regulated and forty-eight genes were down-regulated in ARVC hearts compared with the normal hearts.Changes of gene expressions were most prominently observed in those belonging to the "metabolism" category.Eighty percent of the selected 30 differentially expressed genes from microarray analysis were confirmed by quantitative real time RT-PCR.The highly expressed level of atrial natriuratic peptide (ANP) in ARVC hearts that was confirmed by quantitative real time RT-PCR and immunohistochemistry was reported.Conclusion:For the first time to our knowledge,the altered expressed genes in ARVC hearts compared with the matched normal hearts were identified.The results are the base to further study the molecular mechanism and identify diseased-specific molecular biomarkers in heart failure derived from ARVC.