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Qiu-ping Xie Cheng Xiang Gang Wang Ke-feng Lei Yong Wang 《Journal of Zhejiang University. Science. B》2016,17(5):361-366
In various studies, metastasis associated with colon cancer 1 (MACC1) has been frequently reported to be abnormally highly expressed in human lung cancer, colon cancer, and hepatocellular carcinoma. Our study focuses on the association of MACC1 expression with gastric cancer (GC). During our experiment, the MACC1 expression was tested in 105 GC samples using an immunohistochemical (IHC) method. The clinical characteristics and prognosis of these patients were summarized. During analysis, MACC1 distribution in GC samples with distant metastasis was higher than that in normal samples and in tumors with no dissemination. Subsequently, a lower 5-year survival rate had a strong correlation with high MACC1 expression. As a consequence, the present results suggest that MACC1 is more frequently expressed in a poor prognosis phenotype of GC and acts as a promising prognostic prediction parameter for GC. 相似文献
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Arthur L. Beaudet 《Child development》2013,84(1):121-132
Chromosomal microarray analysis (CMA) has emerged as a powerful new tool to identify genomic abnormalities associated with a wide range of developmental disabilities including congenital malformations, cognitive impairment, and behavioral abnormalities. CMA includes array comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays, both of which are useful for detection of genomic copy number variants (CNV) such as microdeletions and microduplications. The frequency of disease‐causing CNVs is highest (20%–25%) in children with moderate to severe intellectual disability accompanied by malformations or dysmorphic features. Disease‐causing CNVs are found in 5%–10% of cases of autism, being more frequent in severe phenotypes. CMA has replaced Giemsa‐banded karyotype as the first‐tier test for genetic evaluation of children with developmental and behavioral disabilities. 相似文献
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Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies. 相似文献
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Jiang Shuai Zhang Wenyuan Lu Yuanqiang 《Journal of Zhejiang University. Science. B》2022,23(12):1028-1041
Due to the low specificity and sensitivity of biomarkers in sepsis diagnostics, the prognosis of sepsis patient outcomes still relies on the assessment of clinical symptoms. Inflammatory response is crucial to sepsis onset and progression; however, the significance of inflammatory response-related genes (IRRGs) in sepsis prognosis is uncertain. This study developed an IRRG-based signature for sepsis prognosis and immunological function. The Gene Expression Omnibus (GEO) database was retrieved for two sepsis microarray datasets, GSE64457 and GSE69528, followed by gene set enrichment analysis (GSEA) comparing sepsis and healthy samples. A predictive signature for IRRGs was created using least absolute shrinkage and selection operator (LASSO). To confirm the efficacy and reliability of the new prognostic signature, Cox regression, Kaplan-Meier (K-M) survival, and receiver operating characteristic (ROC) curve analyses were performed. Subsequently, we employed the GSE95233 dataset to independently validate the prognostic signature. A single-sample GSEA (ssGSEA) was conducted to quantify the immune cell enrichment score and immune-related pathway activity. We found that more gene sets were enriched in the inflammatory response in sepsis patient samples than in healthy patient samples, as determined by GSEA. The signature of nine IRRGs permitted the patients to be classified into two risk categories. Patients in the low-risk group showed significantly better 28-d survival than those in the high-risk group. ROC curve analysis corroborated the predictive capacity of the signature, with the area under the curve (AUC) for 28-d survival reaching 0.866. Meanwhile, the ssGSEA showed that the two risk groups had different immune states. The validation set and external dataset showed that the signature was clinically predictive. In conclusion, a signature consisting of nine IRRGs can be utilized to predict prognosis and influence the immunological status of sepsis patients. Thus, intervention based on these IRRGs may become a therapeutic option in the future.
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Yi-ping Tian Ai-fen Lin Mei-fu Gan Hao Wang Dan Yu Chong Lai Dan-dan Zhang Yi-min Zhu Mao-de Lai 《Journal of Zhejiang University. Science. B》2017,18(9):747-756
Aberrant DNA methylation has raised widespread attention in tumorigenesis. In this study, we aimed to investigate the changes of global DNA methylation and hydroxymethylation from normal to tumor tissues in colorectal cancer (CRC) and their association with the prognosis. The levels of genomic 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in cancerous tissues were significantly lower than those in corresponding adjacent normal tissues. The genomic levels of 5mC were significantly positively correlated with 5hmC in normal and cancerous tissues (all P<0.05). The ratio of 5mC in cancerous tissues to matched normal tissues (C/N-5mC) was also significantly positively correlated with the ratio of 5hmC in cancerous tissues to matched normal tissues (C/N-5hmC) (P=0.01). The 5mC levels and C/N-5mC ratios decreased with age (all P<0.05). Higher 5mC and 5hmC levels were found in rectal than in colon tissues (all P<0.05). High levels of 5mC in cancerous tissues and high C/N-5hmC ratios were each associated with lymph node metastasis (all P<0.05). Survival analysis indicated that the C/N-5mC ratio (P=0.04) is an independent protective factor for overall survival. The data showed that patients with a combination of high C/N-5hmC and low C/N-5mC ratios tended to have a worse prognosis (P<0.01). Our findings showed that the C/N-5mC ratio may be an independent prognostic factor for CRC outcome. Patients with both a high C/N-5hmC ratio and a low C/N-5mC ratio exhibited the worst survival, suggesting that 5mC and 5hmC can be used as critical markers in tumorigenesis and prognosis estimation. 相似文献
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目的:基于网络药理学方法探讨威灵仙抗结直肠癌可能的分子机制。方法:通过TCMSP数据库挖掘获取威灵仙活性成分,限定口服利用度(OB)和类药性(DL)数值对威灵仙活性成分进行筛选。利用TCMSP搜索威灵仙相关靶基因,GeneCards数据库收集与结直肠癌相关的基因,采用Cytoscape Version 3.7.1软件,构建威灵仙活性成分-抗结直肠癌靶点网络。使用String数据库构建蛋白质相互作用网络。使用Bioconductor数据库对威灵仙抗结直肠癌作用靶点进行基因本体(GO)富集分析与KEGG通路分析,以探究威灵仙抗结直肠癌的作用机制。结果:收集到57种化合物,经筛选和分析获得威灵仙活性成分7个,涉及抗结直肠癌作用靶点30个,关键靶点包括CASP3、JUN、ADRA1B、MAOA等。GO功能富集分析得到GO条目55个,KEGG通路富集筛选得到61条信号通路,包括凋亡通路、p53信号通路、结直肠癌信号通路等。结论:威灵仙治疗结直肠癌具有多通路、多靶点作用的特点,其具体的调控机制及关键的靶标尚待通过进一步的实验研究加以探索及验证。 相似文献
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Objective: To understand the function of nicotinamide N-methyltransferase (NNMT) protein as tumor biomarker in renal carcinoma. Methods: Recombinant NNMT protein was used to prepare monoclonal antibodies by hybridoma technique. The diagnostic and prognostic function of NNMT protein in renal carcinoma was evaluated by analyzing 74 renal cancer tissues through immunohistochemical staining for NNMT by using the prepared antibodies. Results: Two hybridomas named 2F8 and 1E7 stably secreting the monoclonal antibodies were isolated successfully, and characters such as isotypes and specificity were determined. NNMT protein was significantly up-regulated in renal cancer and significantly associated with tumor histology and ages. The univariate survival analysis demonstrated that the pT-status, high levels of NNMT, and distant metastasis were significant prognosticators. Conclusion: NNMT is over-expressed in a large proportion in renal cell cancers. High NNMT expression is significantly associated with unfavorable prognosis. However, the prognostic value of NNMT needs further verification in larger sample sizes. 相似文献
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Co-expression of sCD40LIg and CTLA4Ig mediated by adenovirus prolonged mouse skin allograft survival 总被引：1，自引：0，他引：1
INTRODUCTION Costimulatory signals play a vital role in T cell activation. B7/CD28 and CD40/CD40L have been well-established as important costimulatory pathways, with the blockade of either resulting in suppression or anergy of T cells associated with prolongation of graft survival (Akalin et al., 1996; Bolling et al., 1996; Kita et al., 1999; Reddy et al., 2001; Laumonier et al., 2003; Thiel et al., 2005). Cytotoxic T lymphocyte associated antigen-4 (CTLA4), a ligand for B7, de-… 相似文献
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Two-component genes are kinds of genetic elements involved in regulation of antibiotic production in Streptomyces coelicolor. DNA microarray analysis revealed that ecrA1/A2, which mapped at distant sites from red locus and encode respectively the kinase and regulator, expressed coordinately with genes of Red specific biosynthetic pathway, ecrA1 and ecrA2 gene-disruptive mutants were constructed using homogenotisation by reciprocal double crossover. Fermentation data showed that the undecylprodigiosin (Red) level of production was lower than that of wild-type strain. However, the change of the actinorhodin (Act) production level was not significant compared with wild type. Thus, these experiment results confirmed that the two-component system ecrA 1/A2 was positive regulatory element for red gene cluster. 相似文献
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INTRODUCTION S.coelicolor as a model system has been ex-tensively studied with the aid of genetic and mo-lecular techniques. Its ability to produce four anti-biotics (Hopwood et al., 1995), namely actinorhodin (Act), undecylprodigiosin (Red), Calcium-Depend- ent Antibiotic (CDA) and methylenomycin (Mmy), enables studies of pathyway-specific and pleiotropic regulation of antibiotic production. In which, Red is a red-pigmented antibiotic and Act is coelicolor- pigmented antibiotic tha… 相似文献
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Copy number variants (CNVs) are pieces of genomic DNA of 1000 base pairs or longer which occur in a given genome at a different frequency than in a reference genome. Their importance as a source for phenotypic variability has been recognized only in the last couple of years. Chromosomal deletions can be seen as a special case of CNVs where stretches of DNA are missing in certain lines when compared to the reference genome of the mouse line C57BL/6, for example. Based upon more than 8 million single nucleotide polymorphisms (SNPs) in the fifteen inbred mouse lines which were determined in a whole genome chip based resequencing project by Perlegen Sciences, we detected 20166 such long chromosomal deletions. They cover altogether between 4.4 million and 8.8 million base pairs, depending on the mouse line. Thus, their extent is comparable to that of SNPs. The chromosomal deletions were found by searching for clusters of missing values in the genotyping data by applying bioinformatics and biostatistical methods. In contrast to isolated missing values, clusters are likely the consequence of missing DNA probe rather than of a failed hybridization or deficient oligos. We analyzed these deletion sites in various ways. Twenty-two percent of these deletion sites overlap with exons; they could therefore affect a gene's functioning. The corresponding genes seem to exist in alternative forms, a phenomenon that reminds of the alternative forms of mRNA generated during gene splicing. We furthermore detected statistically significant association between hundreds of deletion sites and fat weight at the age of eight weeks. 相似文献
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前列腺癌作为男性生殖系统好发的恶性肿瘤,其发生及预后的判断直接关系到男性的生存健康。传统的前列腺癌预后评价指标,如TNM分期、Gleason评分和PSA表达水平等,对临床预后判断有一定意义。但近些年大量分子标志物的发现和应用为前列腺癌的预后评估提供了更可靠、更准确的依据。文章对与前列腺癌发生、转移及血管生成等相关的分子标志物作一综述。 相似文献