Exploratory screening of potential pan-cancer biomarkers based on The Cancer Genome Atlas database / 北京大学学报(医学版)

OBJECTIVE@#To screen potential pan-cancer biomarkers based on The Cancer Genome Atlas (TCGA) database, and to provide help for the diagnosis and prognosis assessment of a variety of cancers.@*METHODS@#"GDC Data Transfer Tool" and "GDCRNATools" packages were used to obtain TCGA database. After data sorting, a total of 13 cancers were selected for further analysis. False disco-very rate (FDR) < 0.05 and fold change (FC) >1.5 were used as the differential expression criteria to screen genes and miRNAs that were up- or down-regulated in all the 13 cancers. In the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), the best cut-off value and the corresponding sensitivity and specificity were used to reflect diagnostic significance. The Kaplan-Meier method was used to calculate the survival probability and then the log-rank test was performed. Hazard ratio (HR) was calculated to reflect prognostic evaluation significance. DAVID tool were used to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for differentially expressed genes. STRING and TargetScan tools were used to analyze the regulatory network of differentially expressed genes and miRNAs.@*RESULTS@#A total of 48 genes and 2 miRNAs were differentially expressed in all the 13 cancers. Among them, 25 genes were up-regulated, 23 genes and 2 miRNAs were down-regulated. Most differentially expressed genes and miRNAs had good ability to distinguish between the cases and controls, with AUC, sensitivity and specificity up to 0.8-0.9. Survival analysis results show that differentially expressed genes and miRNAs were significantly associated with patient survival in a variety of cancers. Most up-regulated genes were risk factors for patient survival (HR>1), while most down-regulated genes were protective factors for patient survival (0 < HR < 1). The enrichment analysis of GO and KEGG showed that the differentially expressed genes were mostly enriched in biological events related to cell proliferation. In the regulatory network analysis, a total of 13 differentially expressed genes and 2 differentially expressed miRNAs had regulatory and interaction relationships.@*CONCLUSION@#The 48 genes and 2 miRNAs that were differentially expressed in 13 cancers may serve as potential pan-cancer biomarkers, providing help for the diagnosis and prognosis evaluation of a variety of cancers, and providing clues for the development of broad-spectrum tumor therapeutic targets.

Extraction technique of human genomic DNA from stools and its applications / 中华检验医学杂志

Noninvasive early diagnosis of colorectal cancer is conducive for patients to reduce the mortality rate and their suffering from diagnosis procedures.One of the most significant methods to proceed noninvasive early diagnosis of colorectal cancer is analysis of stool DNA.Extracting high quality and great quantity of human genomic DNA from stools guarantees diagnosis accuracy.However,the complexity of stool component hinders DNA extraction.Hence,it is crucial to develop highly efficient extraction methods of human genomic DNA from stools for the DNA analysis-based early diagnosis of colorectal cancer.Currently,two kinds of extraction strategies are employed:one is to directly extract total DNA from stools,the other is to enrich exfoliated colonocytes in stools before DNA extraction.This article reviews the advances on these two kinds of extraction techniques and summarizes their applications.

Application of array CGH in genetic diagnosis of clinical complex chromosomal abnormalities / 中华检验医学杂志

Objective To evaluate application feasibility of Array CGH in genetic diagnosis of clinical complex chromosomal abnormalities.Methods Two patients of genetic counseling and two patients of prenatal diagnosis were selected from Xiamen Maternity & Child Health Care Hospital during the period of December 2010 to December 2011.Under aseptic conditions 2-4 ml peripheral blood was collected in EDTA and 2-3 ml Cord Blood was collected through cordocentesis after genetic counseling and preoperative examination.G-banded chromosome analysis and genome DNA extraction were carried out on the four cases.The whole genome of four cases were scanned and analyzed by Array CGH.The results of Array CGH were confirmed by FISH.Results Array CGH detected different kinds of duplications and deletions in several chromosomes.Most of these duplications and deletions were not detected by karyotype analysis.The results of Array CGH showed duplication of 4p16.3-4p15.31,deletion of 4p16.3 in the first case,duplication of Xp11.22-Xq11.1 in the second case,duplication of 4p16.3-4p15.32,deletion of 2q37.3 in the third case and duplication of 2q21.2-2q32.1,deletion of 2q14.3-2q21.1 in the fourth case.These duplications and deletions were confirmed by FISH.Conclusions Compared with conventional cytogenetic analysis,Array CGH can not only accurately detect micro deletion and micro duplication with high resolution and sensitivity but also identify breakpoints precisely.Array CGH can provide the basis for clinical genetic diagnosis.

Protection of genetic heritage in the era of cloning

Research on human beings has expanded greatly due to progress and the evolution of society as well as customs. Not only the unceasing development of research on human beings, but also interference in the beginning and end of life with homologous and heterogonous human reproduction, surrogate motherhood, cloning, gene therapies, eugenics,euthanasia, dysthanasia, orthothanasia, assisted suicide, genetic engineering, reassignment surgery in cases of transsexuality, the use of recombinant DNA technology and embryonic stem cells, transplantation of human organs and tissues, biotechnology and many other scientific advances. Scientific progress goes faster than the real needs of human beings, who are the final recipient of the entire evolutionary progress. Hence, there is the need to scrutinize whether new technologies are necessary, suitable and timely so that humanity can achieve its postulate of bene vivere. Human cloning, as an abrupt scientific fact, has presented itself to the world community as a procedure that can be performed with relative success and with little difficulty, since it achieved its objectives with the cloning of Dolly the sheep. This issue became the topic of discussion not only in the scientific community but in the lay population, and it received from both, global disapproval. The conclusion is that the human being is unique, with a life cycle defined by the rules of nature. Reversal will cause a violation of the genetic heritage and, above all, will confront the constitutional principle of human dignity.

Detección de ADN de parvovirus B19 en donantes de sangre de tres hospitales en Santiago, Chile / Parvovirus B19 among blood donors from three hospitals in Santiago, Chile

Background: Parvovirus B19 (B19) is associated with a wide range of diseases in humans, whose severity depends on the immunological and hematological status of the host. It is transmitted mainly through the airway but also by transfusions. Aim: To determine the B19 DNA carrier frequency in a population of volunteer blood donors from three hospitals blood banks in Santiago, Chile, and to determine the viral load in DNA positive cases. Material and Methods: A total of477 serum samples were analyzed. The screening of B19 DNA was carried out by nested polymerase chain reaction (PCR) directed to the non-structural region of the virus (NS1). The viral load in positives cases was quantified by NS1 Real Time PCR. Results: Parvovirus B19 was detected in four samples, rendering a frequency of 1:119. The viral loads ranged from less than 2000 to 5,626 x 10(5) genome equivalents/ml. Conclusions: Parvovirus B19 was present in four of 477 blood bank blood donors from three hospitals in Santiago.

Medicina genômica personalizada aqui e agora / Personal genomic medicine here and now

A Medicina Genômica é uma revolução em curso, baseada em testes genéticos que permitem o conhecimento do mapa de predisposições genéticas de cada indivíduo. O uso de técnicas de altíssima eficiência permite estudar simultaneamente variações individuais em centenas de milhares de genes, a custo cada dia mais baixo. O resultado dos testes possibilita praticar o que antes era impossível: uma medicina verdadeiramente personalizada, preditiva, pró-ativa, preventiva e participativa. Conhecendo a intimidade das variações genômicas que determinam predisposições e resistências de cada pessoa, é possível manipular o ambiente (estilo de vida, dieta, adição ou remoção de fármacos, cirurgias preventivas) de forma a manter o equilíbrio harmônico genoma/ ambiente que caracteriza a saúde. A partir do teste monitor genômico, e acesso à Medicina Genômica personalizada já é possível aqui e agora.

Genomic Medicine is a revolution in progress, based on genetic tests that allow the knowledge of each individual's map of genetic predispositions. Using high efficiency techniques allows the study of individual variations simultaneouslv in hundreds of thousands of genes, each day at a lower cost. The tests results make possible what was once impossible: to practice the actually personalized medicine, predictive, pro-active, preventive and participative. Knowing the privacy of genomic variations that determine biases and strengths of each person, you can manipulate the environment (lifestyle, diet, addition or removal of drugs, preventive surgeries) in order to maintain the harmonious balance genome / environment that characterizes the health. From the genomic test monitor, the access to personalized genomic medicine is already possible here and now.

Embriones híbridos como fuente de células troncales embrionarias: [editorial] / Hybrid embryos as a source of embrionic stem cells: [editorial]

The HFEA (Human Fertilisations & Embryology Authority) recently accepted to perform research in hybrid embryos generated by transferring human somatic cell nucleus to cow enucleated oocytes, named cytoplasmatic hybrids. The aim is to obtain a source of embryonic stem cells without the use of human oocytes. The arguments for the approval are to avoid the risk of obtaining human oocytes and that these embryos will not be transferred to a female's womb for its development. Those who oppose the technique argue that it is a manipulation of the beginning of life and a disrespect to the dignity of human life because of the destruction of embryos. Nevertheless, the real nature of this new entity has not been established. Biologically it is an embryo with 99 percent of human genome and animal's cytoplasm, not generated from human gametes, it is not a new genome and it will be used only to cultivate stem cells. It does not seem possible to define its nature beyond any doubts. If it were considered as a human embryo it should be respected and protected as every human being. Once more, scientific progress opens new ethical and legal questions that we cannot answer in a definitive way. Researchers are exploring new roads to obtain pluripotential stem cells which should favor the development of innovative therapies. The main objection is the unavoidable destruction of human embryos, although in this case its origin and nature are not clear.

WNKs: protein kinases with a unique kinase domain

WNKs (with-no-lysine [K]) are a family of serine-threonine protein kinases with an atypical placement of the catalytic lysine relative to all other protein kinases. The roles of WNK kinases in regulating ion transport were first revealed by the findings that mutations of two members cause a genetic hypertension and hyperkalemia syndrome. More recent studies suggest that WNKs are pleiotropic protein kinases with important roles in many cell processes in addition to ion transport. Here, we review roles of WNK kinases in the regulation of ion balance, cell signaling, survival, and proliferation, and embryonic organ development.