Genomic Medicine, Biomarkers, and Health Sciences最新文献

Alzheimer's disease (AD) is the most common cause of dementia of late life. The aim of this study was to utilize the proteomic approaches to establish serum protein patterns of AD. By using nano-high-performance liquid chromatography/electrospray ionization tandem mass spectrometry followed by peptide fragmentation pattern software to analyze proteome in human serum, the activity-dependent neuroprotector homeobox protein was found to exhibit significant differential expression compared with the control group and was confirmed by Western blotting and enzyme-linked immunosorbent assay. It may play an important role in slowing the progression of clinical symptoms of AD.

Hepatitis B virus plays an important role in persistent inflammation with necrosis of the liver tissue, with the result that some patients with hepatitis develop diabetes. The present study aims to understand the correlation between pro-inflammatory interleukin-6 (IL-6) expression and insulin resistance in hepatitis B patients. Forty-three patients with diabetes, 68 patients with hepatitis, and 68 controls without diabetes and hepatitis were included in this study. The concentrations of glycated hemoglobin, glucose, and insulin antibodies in patients with hepatitis B and diabetes were significantly higher than those in controls without hepatitis and diabetes (p < 0.001). The IL-6 concentrations in the patients with hepatitis B were significantly higher than those in the group with diabetes and the control group. The results suggest that an increase in IL-6 level in hepatitis B patients may lead to the occurrence of high blood glucose levels.

Chronic hepatitis B and C virus (HBV; HBC) infections are worldwide public health challenges. Molecular and genomic biomarkers for the prediction of long-term risk of end-stage liver diseases in patients affected with chronic viral hepatitis are important for the clinical management of the diseases. The REVEAL-HBV/HCV study is a community-based prospective cohort study aimed to evaluate the risk predictors of progression of chronic HBV and HCV in Taiwan. A total of 23,820 participants were enrolled between 1991 and 1992 from seven townships in Taiwan. Their serum samples were collected at study entry and follow-up examinations and tested for antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg) and e antigen (HBeAg), serum levels of alanine aminotransferase (ALT), HCV RNA, HBV DNA, HBsAg, and α-fetoprotein. Genotypes and mutant types of HBV and HCV in serum samples were also examined. Newly developed cases of cirrhosis and hepatocellular carcinoma (HCC) were ascertained through follow-up examination and data linkage with profiles from the National Cancer Registry, National Health Insurance Database, and Death Certification System. Age, sex, elevated serum levels of ALT, HBV DNA and HBsAg, HBeAg serostatus, HBV genotype, family HCC history, and alcohol drinking habits are important biomarkers for the prediction of HBV-related HCC and cirrhosis. Age, elevated serum levels of ALT and HCV RNA, and HCV genotype are important biomarkers for the prediction of HCV-related HCC. Risk calculators have been developed for the long-term risk prediction of HCC for patients with chronic HBV and HCV. These risk calculators have been documented to have good validity for the prediction of risk of HCC and cirrhosis.

Type II diabetes mellitus (T2DM) is one of the most common underdiagnosed metabolic diseases due to lack of recognizable symptoms in the early stage. T2DM can be largely prevented or controlled by diet or regular exercise at early stages, but often goes undetected for years, causing high rates of complications and mortality. Hence, a valid noninvasive early detection approach is urgently needed. In this study, we explored noninvasive detection of T2DM by salivary transcriptomic diagnostics. Salivary mRNA biomarkers were discovered by comparing microarray profiles of salivary transcriptomes in 13 T2DM patients and 13 healthy controls. The marker candidates selected from the microarray analysis were then subjected to verification in the original 26 samples using reverse transcription quantitative real-time polymerase chain reaction. Four up-regulated and two down-regulated mRNA biomarkers were validated. The logistic regression model showed that the combination of four identified biomarkers (KRAS, SAT1, EGFR, and PSMB2) could significantly distinguish T2DM patients from the healthy controls, yielding a receiver-operating characteristic-plot area-under-the-curve value of 0.917 with 100% sensitivity and 77% specificity. In conclusion, RNA signatures in saliva could serve as biomarkers for the detection of T2DM with high sensitivity and specificity, and offer a feasible means for early T2DM detection.

Human uterine cancer occurs most often in menopause women between the ages of 55 and 70 years. In the initial stage, the symptoms of uterus have an abnormal vaginal bleeding or abnormal discharge, and the common treatment is to remove the uterus or treat with chemotherapeutic drugs. For most type of cancers, doxorubicin is frequently prescribed for treating a wide range of various types of cancers, including hematologic malignancies, lymphoma, myeloma, sarcoma, and uterine cancer. However, most cancer cells will become drug insensitivity or resistance via unknown mechanisms. Since mitochondria play a crucial role in the induction apoptosis, it is intriguing to clarify whether doxorubicin-resistance is mediated through mitochondrial protection. In this study, a highly doxorubicin-resistant cell line has been established by continuously culturing the MES-SA/Dx5, a commercial doxorubicin-resistant human uterine cancer cell line, in the presence of doxorubicin for up to 2 years. Mitochondrial proteins from nondrug-resistant MES-SA, low resistant MES-SA/Dx5 (MES-SA/Dx5^low), and high resistant MES-SA/Dx5 (MES-SA/Dx5^high) were enriched, and mitochondrial proteome is characterized by two dimensional-differential gel electrophoresis and matrix-assisted laser desorption/ ionization time of flight mass spectrometer (MALDI-TOF MS).

Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in many parts of the world. It is also often associated with steatosis and other alterations of lipid metabolism, such as hypocholesterolemia. To identify the potential biomarkers for HCV-associated diseases, we have used various approaches to identify the cellular factors involved in HCV replication and pathogenesis. These factors may serve as the biomarkers for various stages of the disease. We have approached this question by identifying cellular proteins coimmunoprecipitated with the viral proteins. We also screened for cellular factors by performing genome-wide or functional subset inhibitory RNA (RNAi) library screening. Many cellular proteins have been identified, among which are proteins belonging to the vesicular transport pathway. For example, vesicle-associated membrane protein (VAMP)-associated vesicular proteins A and B (VAP-A and -B) were found to be required for HCV replication. We also found that HCV RNA replication takes place on the lipid rafts in an induced double-membraned vesicle (termed the “membranous web”). Correspondingly, several cellular proteins involved in the vesicle formation and lipid raft rearrangement were found to be relocalized or induced in HCV-infected cells. Among these are proline-serine-threonine phosphatase-interacting protein-2, a membrane-deforming protein, annexin A2 (a lipid raft organizer), and phosphatidyl inositol phosphate-4, a membrane component. The identification of the essential roles of these proteins in HCV replication indicates that the intracellular membrane and lipid metabolism undergo drastic reorganization during HCV infection. These and the related proteins may serve as biomarkers for HCV infection and disease progression.

Colorectal cancer (CRC) has high recurrence rate.Effective biomarkers for the detection of colon cancer are still unavailable. MicroRNA (miRNA) is an epigenetic factor that regulates cell proliferation, tumor cell growth, cancer formation, and metastasis by regulating tumor suppressor genes or oncogenes. miRNA has the potential to be used as a biomarker for the diagnosis of diverse cancers. Previously, we revealed that miR-139-3 p is downregulated and miR-338-5 p is upregulated in recurrent CRC patients. The present study further reveals that the miR-139-3 p expression level is inversely correlated with increased metastatic status in three colon cancer cell lines (SW480, SW620, and colo201), as determined using real-time polymerase chain reaction. Furthermore, in 51 pairs of CRC clinical specimens, the expression level of mir-139-3 p was significantly lower in the tumor sections than in the adjacent normal tissues (p < 0.0001), indicating that they are tumor-suppressive miRNAs. Furthermore, the expression level of mir-338-5 p in the tumor tissues of metastatic patients was significantly higher than in the tumor tissues of nonmetastatic patients (p < 0.05), indicating that mir-338-5 p is positively correlated with metastasis. All together, mir-139-3 p and mir-338-5 p may have potential use as biomarkers for the diagnosis of tumor formation and metastasis in CRC patients.

Drug resistance is an obstacle to successful cancer treatment. In hematological neoplasms, such as chronic myelogenous leukemia (CML), drug resistance is often associated with gene hypermethylation and loss of function. An imatinib-resistant subclone of CML-like K562 (K562-R) was used as a model to study the role of hypermethylation in drug resistance. K562-R was selected by culturing cells with increasing concentrations of imatinib, ranging from 0.2–5 μM. A DNA methylation microarray was performed on the K562-R and parental K562 cells, and selected gene expression levels were confirmed using real-time polymerase chain reaction. The methylation level was significantly increased and the gene expression level significantly was decreased for MLH1, RPRM, FEM1B, and THAP2 in K562-R cells compared with parental K562 cells. Exposing K562-R cells to methylation inhibitors, such as 5-azacytidine (AzaC) and trichostatin A (TSA), reduced imatinib resistance. Our approach of using a drug-limiting dilution model followed by the use of a methylation microarray was able to identify methylation biomarkers for drug resistance. Specifically, MLH1, RPRM, FEM1B, and THAP2 might be potential epigenetic targets of imatinib resistance. Further understanding the methylation domain and epigenetic regulation machinery of these biomarkers will help researchers find potential effective therapeutic strategies that could be used to overcome drug resistance in CML patients.

In the present study, multiple chemotherapeutic agent-related genetic polymorphisms, including dihydropyrimidine dehydrogenase (DPD) IVS14+1 G>A, UGT1A1 3156 G>A, and UDP-glucuronosyltransferase (UGT)1A1 28 tandem repeats, were analyzed in patients with colorectal cancer and studied in correlation with the clinical features of those patients. The genotypes from 273 patients with stages I–IV colorectal cancer who underwent operations were determined by means of polymerase chain reaction-restriction fragment length polymorphism. The results showed that the genotype distribution of DPD GG, UGT1A1 3156 GG, and UGT1A1 28 tandem repeats 5/6 or 6/6 in Taiwanese subjects were 98.4%, 82.2%, and 80.6%, respectively. After analysis of the relationship between the genotypes and clinicopathological data of the patients, a significant correlation was observed between vascular invasion in patients with genetic polymorphisms ofDPDGG, UGT1A13156GG, and UGT1A1 28 repeat 5/6 or 6/6 (OR: 2.236, p = 0.015). There was a statistical correlation between vascular invasion and tumor invasion, lymph node metastasis, cancer stage, differentiation, perineural invasion, and survival (all p < 0.05). The results of the present study highly suggest that DPDGG, UGT1A13156GG, and UGT1A1 28 repeat 5/6 or 6/6 genotypes and vascular invasion could be prognostic factors for Taiwanese patients with colorectal cancer.

We report herein the case of a 42-year-old woman having thyroid diffuse large B-cell lymphoma with initial presentation of right neck mass. After cytology and immunohistochemical profiles confirmed the diagnosis of a primary thyroid lymphoma, she received regional surgical excision, adjuvant radiotherapy, and systemic chemotherapy.