Neuroblastoma (NBL) is the most frequently encountered extracranial solid neoplasm and impacts significantly on the survival of patients, especially in cases of advanced tumor stage or relapse. A long noncoding RNA (lncRNA) signature to predict the survival of patients with NBL is proposed in this paper. Differentially expressed lncRNA (DElncRNA) was selected using the Limma plus Voom package in R based on the RNA-sequencing data downloaded from the Therapeutically Applicable Research To Generate Effective Treatments database and Genotype-Tissue Expression database. Univariate cox regression analysis, least absolute shrinkage and selection operator regression analysis, and multivariate cox regression analysis were conducted to identify candidate DElncRNAs for the risk signature. Consequently, 10 DElncRNAs were designated as candidate DElncRNAs for the risk signature. Time-dependent receiver operating characteristic curves and Kapan-Meier survival curves confirmed the efficacy of the risk signature in predicting the survival of patients with NBL (area under the curve = 0.941; p ≤ .001). One of the DElncRNA constituent subparts (LINC01010) was significantly associated with the survival outcome of patients with NBL in GSE62564 (p = .004). Thus, a risk signature comprising 10 DElncRNAs was identified as effective for individual risk stratification and the survival prediction outcomes of patients with NBL.
Binary communication systems that involve sex‐specific signaling and sex‐specific signal perception play a key role in sexual selection and in the evolution of sexually dimorphic traits. The driving forces and genetic changes underlying such traits can be investigated in systems where sex‐specific signaling and perception have emerged recently and show evidence of potential coevolution. A promising model is found in Drosophila prolongata, which exhibits a species‐specific increase in the number of male chemosensory bristles. We show that this transition coincides with recent evolutionary changes in cuticular hydrocarbon (CHC) profiles. Long‐chain CHCs that are sexually monomorphic in the closest relatives of D. prolongata (D. rhopaloa, D. carrolli, D. kurseongensis, and D. fuyamai) are strongly male‐biased in this species. We also identify an intraspecific female‐limited polymorphism, where some females have male‐like CHC profiles. Both the origin of sexually dimorphic CHC profiles and the female‐limited polymorphism in D. prolongata involve changes in the relative amounts of three mono‐alkene homologs, 9‐tricosene, 9‐pentacosene, and 9‐heptacosene, all of which share a common biosynthetic origin and point to a potentially simple genetic change underlying these traits. Our results suggest that pheromone synthesis may have coevolved with chemosensory perception and open the way for reconstructing the origin of sexual dimorphism in this communication system.
This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. Methods: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. Results: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients' age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. Conclusion: The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.
The use of mRNAs as biomarkers serves to diagnose, treat, as well as aid the prognosis of cancer. The present study involved an analysis of mRNAs in the cell cycle at the G2 and G3 tumor grades for the prognosis of ovarian serous cystadenocarcinoma (OSC) using 364 clinical samples (G2:G3=42:322). Statistics aided the identification of NPFFR2, XPNPEP2 and CELA3B; the 3-mRNA model that allows for classification of patients into high- and low-risk groups using a median value of 0.9580745. The rates of survival varied (P=0.00149) and the independent detection of stratification of the risk of this disease was validated with success using the 3-mRNA signature, which was demonstrated to be more successful than the weight model. This approach was revealed to provide the prognosis of grade G2 and G3 in patients with OSC compared with factors used traditionally. Compared with traditional factors, this 3-mRNA model was demonstrated to be the only and independent prognostic factor for patients with G2 and G3 stage OSC. A literature survey was also performed in the present study in order to assess the role of the 3 genes and indirectly prove their effectiveness. The establishment of this new genetic model will enhance prospective prognosis and treatment for patients with OSC.
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The funding was mainly used for data analysis and interpretation, and the costs incurred during the manuscript preparation Background:Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. Material/Methods:Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. Results:From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. Conclusions:RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.
We explored the difference in expression of tubulin alpha 1b (TUBA1B) between Wilms’ tumor (WT) and normal tissues (NT) from in-house patients and databases, to determine TUBA1B expression in WT and the predictive pathways of coexpressed genes. In-house RNA-sequencing data were performed with WT and NT from three patients from our institute. Other four RNA-sequencing and microarray data were also downloaded from multiple public databases. The TUBA1B expression between WT and NT was analyzed by Student’s t-test and meta-analysis. The correlation between the expression of TUBA1B and other genes in each study was analyzed. Genes with p<0.05 and r>0.5 were considered as the coexpressing genes of TUBA1B. Overlapping the coexpressed genes of the five studies, including three in-house patients (3 WT vs. 3 NT), GTEx-TARGET (126 WT vs. 51 NT), GSE2172 (18 WT vs. 3 NT), GSE11024 (27 WT vs. 12 NT), and GSE73209 (32 WT vs. 6 NT), were performed with limma and VennDiagram packages in R software. The website of WEB-based GEne SeT AnaLysis toolkit were used to analyze the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations for the overlapped genes. The results showed that the relative expression of TUBA1B in WT tissues from in-house three patients was 280.0086, 141.7589, and 303.8292 and that in NT was 16.5836, 104.8141, and 12.79 (3 WT vs. 3 NT, p=0.0285, ROC=100%, SMD=2.74). Student’s t-test and meta-analysis in all studies revealed that the expression of TUBA1B was upregulated in WT tissues compared to that in NT (p<0.05, SMD=2.89, sROC=0.98). Finally, the research identified the expression of TUBA1B in WT tissues was significantly upregulated than that in NT. The coexpressed genes of TUBA1B were enriched in the pathway of DNA replication, mismatch repair, cell cycle, pathogenic Escherichia coli infection, and spliceosome.
Apolipoprotein E (apoE), one of the major plasma lipoproteins, plays a major role in the transport and metabolism of lipids by acting as a ligand. apoE gene contains three potential alleles: e2, e3 and e4, forming six genotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Association between apoE gene polymorphism and triglyceride (TG) is still controversial. There was no any meta-analysis to explore the association of apoE gene polymorphism with triglyceride level, and this meta-analysis was performed to evaluate the association between apoE gene polymorphism and triglyceride in patients with renal diseases. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Twenty-four articles were identified for the analysis of association between apoE gene polymorphism and triglyceride level. Subjects with E2E3 or E3E4 had a higher TG than those with E3E3. Subjects with e4 had a higher TG than those with e3. Subjects with e2 had a slightly higher TG than those with e3, although there was no statistical difference. Interestingly, subjects with e4 had a much higher TG than those with e2. In conclusion, E2E3, E3E4 or e4 was associated with higher level of TG. However, more studies should be performed in the future.
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