Cancer diagnosis marker extraction for soft tissue sarcomas based on gene expression profiling data by using projective adaptive resonance theory (PART) filtering method

BACKGROUND: Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis and selection of treatment. To accomplish this objective, it is important to establish a sophisticated algorithm that can deal with large quantities of data such as gene expression profiles obtained by DNA microarray analysis. RESULTS: Previously, we developed the projective adaptive resonance theory (PART) filtering method as a gene filtering method. This is one of the clustering methods that can select specific genes for each subtype. In this study, we applied the PART filtering method to analyze microarray data that were obtained from soft tissue sarcoma (STS) patients for the extraction of subtype-specific genes. The performance of the filtering method was evaluated by comparison with other widely used methods, such as signal-to-noise, significance analysis of microarrays, and nearest shrunken centroids. In addition, various combinations of filtering and modeling methods were used to extract essential subtype-specific genes. The combination of the PART filtering method and boosting – the PART-BFCS method – showed the highest accuracy. Seven genes among the 15 genes that are frequently selected by this method – MIF, CYFIP2, HSPCB, TIMP3, LDHA, ABR, and RGS3 – are known prognostic marker genes for other tumors. These genes are candidate marker genes for the diagnosis of STS. Correlation analysis was performed to extract marker genes that were not selected by PART-BFCS. Sixteen genes among those extracted are also known prognostic marker genes for other tumors, and they could be candidate marker genes for the diagnosis of STS. CONCLUSION: The procedure that consisted of two steps, such as the PART-BFCS and the correlation analysis, was proposed. The results suggest that novel diagnostic and therapeutic targets for STS can be extracted by a procedure that includes the PART filtering method

Copper-Catalyzed Arylstannylation of Arynes in Sequence

Copper-catalyzed arylstannylation of arynes has been developed. This transformation enables variously substituted ortho-stannylbiaryls and teraryls to be constructed straightforwardly. An electron-deficient tin center is the key, and thus the single or dual insertion of arynes into arylstannanes is precisely controllable by simply changing the equivalence of aryne precursors.This work was financially supported by JSPS KAKENHI Grant Number JP17K05864

Negative correlation between cerebrospinal fluid oxytocin levels and negative symptoms of male patients with schizophrenia

Background: Accumulating evidence indicates that oxytocin plays an important role in social interactions. Previous studies also suggest altered oxytocin function in patients with schizophrenia and depression. However, few studies have examined the central oxytocin levels in these disorders. Methods: Cerebrospinal fluid (CSF) oxytocin levels were measured by ELISA in male participants consisting of 27 patients with schizophrenia, 17 with major depressive disorder (MDD), and 21 healthy controls. Results: CSF oxytocin levels of patients with schizophrenia or MDD did not differ significantly with healthy controls. The antidepressant dose or the Hamilton depression rating scale score did not significantly correlate with the oxytocin levels in MDD patients. CSF oxytocin levels in schizophrenic patients significantly negatively correlated with second generation antipsychotic dose (r=-0.49, P=0.010) but not with first generation antipsychotic dose (r=-0.13, P=0.50). A significant correlation was observed between oxytocin levels and negative subscale of PANSS (r=-0.38, P=0.050). This correlation remained significant even after controlling for second generation antipsychotic dose (r=-0.47, P=0.016). Conclusions: We obtained no evidence of altered CSF oxytocin levels in patients with schizophrenia or those with MDD. However, lower oxytocin levels may be related to higher second generation antipsychotic dose and more severe negative symptoms in schizophrenia.ArticleSCHIZOPHRENIA RESEARCH. 139(1-3):201-206 (2012)journal articl

Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder

信州大学博士（医学）・学位論文・平成25年3月31日授与（甲第944号）・篠山 大明Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls. Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027; MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels. The present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD, although confounding effect of smoking status can not be entirely excluded. (C) 2012 Elsevier Ltd. All rights reserved.ArticleJOURNAL OF PSYCHIATRIC RESEARCH. 47(3):401-406 (2013)journal articl

Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome

There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a BRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic BRCA2 variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls

Pathogenic variants in highly penetrant genes are useful for the diagnosis, therapy, and surveillance for hereditary breast cancer. Large-scale studies are needed to inform future testing and variant classification processes in Japanese. We performed a case-control association study for variants in coding regions of 11 hereditary breast cancer genes in 7051 unselected breast cancer patients and 11,241 female controls of Japanese ancestry. Here, we identify 244 germline pathogenic variants. Pathogenic variants are found in 5.7% of patients, ranging from 15% in women diagnosed <40 years to 3.2% in patients ≥80 years, with BRCA1/2, explaining two-thirds of pathogenic variants identified at all ages. BRCA1/2, PALB2, and TP53 are significant causative genes. Patients with pathogenic variants in BRCA1/2 or PTEN have significantly younger age at diagnosis. In conclusion, BRCA1/2, PALB2, and TP53 are the major hereditary breast cancer genes, irrespective of age at diagnosis, in Japanese women

Construction of possible integrated predictive index based on EGFR and ANXA3 polymorphisms for chemotherapy response in fluoropyrimidine-treated Japanese gastric cancer patients using a bioinformatic method

Selected genetic and clinical parameters of gastric cancer patients. (XLS 33 kb

A complex rearrangement between APC and TP63 associated with familial adenomatous polyposis identified by multimodal genomic analysis: a case report

Genetic testing of the APC gene by sequencing analysis and MLPA is available across commercial laboratories for the definitive genetic diagnosis of familial adenomatous polyposis (FAP). However, some genetic alterations are difficult to detect using conventional analyses. Here, we report a case of a complex genomic APC-TP63 rearrangement, which was identified in a patient with FAP by a series of genomic analyses, including multigene panel testing, chromosomal analyses, and long-read sequencing. A woman in her thirties was diagnosed with FAP due to multiple polyps in her colon and underwent total colectomy. Subsequent examination revealed fundic gland polyposis. No family history suggesting FAP was noted except for a first-degree relative with desmoid fibromatosis. The conventional APC gene testing was performed by her former doctor, but no pathogenic variant was detected, except for 2 variants of unknown significance. The patient was referred to our hospital for further genetic analysis. After obtaining informed consent in genetic counseling, we conducted a multigene panel analysis. As insertion of a part of the TP63 sequence was detected within exon16 of APC, further analyses, including chromosomal analysis and long-read sequencing, were performed and a complex translocation between chromosomes 3 and 5 containing several breakpoints in TP63 and APC was identified. No phenotype associated with TP63 pathogenic variants, such as split-hand/foot malformation (SHFM) or ectrodactyly, ectodermal dysplasia, or cleft lip/palate syndrome (EEC) was identified in the patient or her relatives. Multimodal genomic analyses should be considered in cases where no pathogenic germline variants are detected by conventional genetic testing despite an evident medical or family history of hereditary cancer syndromes

Team Characteristics for Maximizing the Educational Effectiveness of Practical Lectures on Software Intensive Systems Development

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