Clinical and biological impact of LINC02544 expression in breast cancer after neoadjuvant chemotherapy.

OBJECTIVE: Analysis of breast cancer and cancer tissue after neoadjuvant chemotherapy (nCT) may be helpful to find new biomarkers. It is known that long non-coding RNAs (lncRNAs) are involved in the carcinogenic pathway and drug resistance of breast cancer. Our aim was to determine the role of LINC02544 in the behavior and outcome of post-nCT breast cancer. PATIENTS AND METHODS: The expression level of LINC02544 in breast cancer and its effect on the survival time of patients were predicted by lnCAR database. In vitro, EdU, Wound-healing and transwell assays were used to detect the effects of LINC02544 on the proliferation, migration and invasion of MCF-7 cells, and the related regulatory networks were analyzed by the database. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (QRT-PCR) was used to detect the expression of LINC02544 in 147 cases of nCT before and after treatment, and the relationship between the expression of LINC02544 and survival time and clinicopathological features was analyzed. RESULTS: LINC02544 was highly expressed in breast cancer and led to poor prognosis. Overexpression of LINC02544 promoted proliferation, invasion and migration of breast cancer cells. Compared with the residual tumor after nCT with low expression of LINC02544, the high expression of LINC02544 in the residual tumor after nCT was significantly correlated with overall survival and disease-free survival. CONCLUSIONS: In this study, it is suggested that LINC02544 has a potential application prospect as a biomarker and therapeutic target for breast cancer patients and neoadjuvant therapy patients.

INSR gene polymorphisms correlate with sensitivity to platinum-based chemotherapy and prognosis in patients with epithelial ovarian cancer.

This study aimed to investigate the correlation between INSR gene polymorphisms on platinum-based chemotherapy sensitivity and prognosis in epithelial ovarian cancer (EOC). A total of 339 EOC patients receiving postoperative chemotherapy were recruited for the study. Tag single-nucleotide polymorphism of INSR gene was screened from HapMap combined with available literature. Frequency distribution of genotypes and alleles in INSR gene was sequenced by ABI3100-Avant. Compared with CC+GC genotype, INSR rs2252673 GG genotype and rs3745546 CC genotype showed less platinum-based chemotherapy sensitivity in EOC patients (odds ratio (OR)=0.269, 95% confidence interval (CI)=0.159~0.456; OR=0.445, 95% CI=0.214~0.926, respectively), as well as serous EOC patients (OR=0.083, 95% CI=0.024~0.278; OR=0.235, 95%CI=0.053~1.041, respectively). The clinical characteristics including age, clinical stage, histological grade and residual lesion size were significantly related with chemosensitivity to platinum drugs and mortality in EOC patients. According to Kaplan-Meier curve, compared with CC+GC genotype, rs2252673 GG genotype showed significantly decreased survival rate in EOC patients (P<0.05). Cox regression model indicated that rs2252673, age and clinical stage were independent risk factors for the prognosis in EOC (all P<0.05). These findings indicate that INSR rs2252673 and rs3745546 polymorphisms were associated with sensitivity to platinum-based chemotherapy in EOC patients and rs2252673 polymorphism may be an independent risk factor for EOC prognosis.

Integrated systems pharmacology analysis of clinical drug-induced peripheral neuropathy.

A systems pharmacology approach was undertaken to define and identify the proteins/genes significantly associated with clinical incidence and severity of drug-induced peripheral neuropathy (DIPN). Pharmacological networks of 234 DIPN drugs, their known targets (both intended and unintended), and the intermediator proteins/genes interacting with these drugs via their known targets were examined. A permutation test identified 230 DIPN-associated intermediators that were enriched with apoptosis and stress response genes. Neuropathy incidence and severity were curated from drug labels and literature and were used to build a predictive model of DIPN using a regression tree algorithm, based on the drug targets and their intermediators. DIPN drugs whose targets interacted with both v-myc avian myelocytomatosis viral oncogene homolog (MYC) and proliferating cell nuclear antigen-associated factor (PAF15) were associated with a neuropathy incidence of 38.1%, whereas drugs interacting only with MYC had an incidence of 2.9%. These results warrant further investigation in order to develop a predictive tool for the DIPN potential of a new drug.

SZGR: a comprehensive schizophrenia gene resource.

Schizophrenia is a major debilitating psychiatric disorder affecting approximately 1% of the population worldwide. A tremendous amount of effort has been expended in the last two decades to identify genes influencing susceptibility to this disorder. Although there is a strong trend toward integrating data obtained from various genetic studies and their related biological information into a comprehensive resource for many complex diseases, we were unable to find such an effort for schizophrenia or for any other psychiatric disorder yet. In this study, we present Schizophrenia gene resource (SZGR), a comprehensive database with user-friendly web interface. SZGR deposits genetic data from all available sources, including those from association studies, linkage scans, gene expression, literature, gene ontology (GO) annotations, gene networks, cellular and regulatory pathways, as well as microRNAs and their target sites. Moreover, SZGR provides online tools for data browse and search, data integration, custom gene ranking and graphical presentation. This system can be easily applied to other complex diseases, especially to other psychiatric disorders. The SZGR database is available at http://bioinfo.mc.vanderbilt.edu/SZGR/.

The dystrobrevin-binding protein 1 gene: features and networks.

The dystrobrevin-binding protein 1 (DTNBP1) gene has been one of the most studied and promising schizophrenia susceptibility genes since it was first reported to be associated with schizophrenia in the Irish Study of High Density Schizophrenia Families (ISHDSF). Although many studies have been performed both at the functional level and in association with psychiatric disorders, there has been no systematic review of the features of the DTNBP1 gene, protein or the relationship between function and phenotype. Using a bioinformatics approach, we identified the DTNBP1 gene in 13 vertebrate species. The comparison of these genes revealed a conserved gene structure, protein-coding sequence and dysbindin domain, but a diverse noncoding sequence. The molecular evolutionary analysis suggests the DTNBP1 gene probably originated in chordates and matured in vertebrates. No signature of recent positive selection was seen in any primate lineage. The DTNBP1 gene likely has many more alternative transcripts than the current three major isoforms annotated in the NCBI database. Our examination of risk haplotypes revealed that, although the frequency of a single nucleotide polymorphism (SNP) or haplotype might be significantly different in cases from controls, difference between major geographic populations was even larger. Finally, we constructed the first DTNBP1 interactome and explored its network features. Besides the biogenesis of lysosome-related organelles complex 1 and dystrophin-associated protein complex, several molecules in the DTNBP1 network likely provide insight into the role of DTNBP1 in biological systems: retinoic acid, beta-estradiol, calmodulin and tumour necrosis factor. Studies of these subnetworks and pathways may provide opportunities to deepen our understanding of the mechanisms of action of DTNBP1 variants.

Effects of aminoglutethimide on hypothalamic-pituitary-adrenal functions.

This study was performed on four groups of subjects, including 10 patients with Cushing's disease, 10 patients with simple obesity, 8 patients with hypopituitarism and 13 normal subjects. The study was conducted by measuring the sequential changes of plasma ACTH, serum cortisol, 24-h UFC, 24-h 17 KS and 24-h 17 KGS following aminoglutethimide (AG) administration. The results suggest that normal subjects showed sequential changes of hypothalamic-pituitary-adrenal hormone concentrations with normal feedback regulation of the axis following AG administration. Patients with Cushing's disease had obvious autonomy in the production of ACTH from the pituitary. Patients with simple obesity might display abnormality to some degree in the production from the pituitary. Patients with hypopituitarism lost the capacity of ACTH production in various degrees because of pituitary lesions.