Study on the Difference of Gene Expression Between Left and Right Colon Cancer and the Mechanism of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba Based on TCGA / 广州中医药大学学报

Abstact:Objective To investigate the gene expression differences between left-sided colon cancer and right-sided colon cancer and the mechanism differences between the colorectal cancer core drug pairs of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba acting on left-sided and right-sided colon cancer.Methods The transcriptome data of 134 patients with left-sided colon cancer and 194 patients with right-sided colon cancer from The Cancer Genome Atlas(TCGA)were downloaded,and the R software was applied to realize the differential gene analysis of the two groups and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway;the BATMAN-TCM database was used to obtain the active ingredients and targets of the drug pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,and based on the different genes of the left-and right-sided colon cancers,KEGG enrichment analysis of the drug pair-left/right-sided colon cancers was performed respectively,and the protein-protein-interaction(PPI)network was constructed to compare the differences of the biosignaling pathways enriched by the drug pairs for the treatment of left-and right-sided colon cancers,as well as the differences of the key target points.Results There were 6 051 differentially expressed genes common to left-and right-sided colon cancers relative to normal paracancerous tissues,1958 differentially expressed genes specific to left-sided colon cancer,and 1739 differentially expressed genes specific to right-sided colon cancer;14 KEGG-enriched pathways specific to left-sided colon cancer,and 23 KEGG-enriched pathways specific to right-sided colon cancer.There were 85 active compounds in the drug-pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,corresponding to a total of 469 targets.The drug-pair-left-sided colon cancer targets were enriched in 10 KEGG signaling pathways,with the key targets being DRD2,CACNA1C,HTR3A,COMT,and TH;and the drug-pair-right-sided colon cancer targets were enriched in 1 KEGG signaling pathway,with the core targets being HTR3A,DRD2 TH,AGT,GRIN2B.Conclusion There are gene expression differences between left-and right-sided colon cancers:left-sided colon cancer is associated with abnormal immune function,abnormal AMPK signaling pathway and other mechanisms,and right-sided colon cancer is associated with neutrophil extracellular trap formation,alcoholism,abnormal Hippo signaling pathway and other mechanisms.In addition to regulating cell cycle and essential amino acid metabolism and other mechanisms,Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba drug pairs have specific effects on regulating the intestinal endocrine function of the left-sided colon cancer,inhibiting inflammatory response of the right-sided colon cancer,and may also have mood-regulating effects on patients with colon cancer.

Correlation of RBP7 mRNA Expression in Breast Cancer Tissues with Tumor Immune Cell Infiltration and Prognosis Based on TCGA Database / 现代检验医学杂志

Objective To explore the role of retinol binding protein 7(RBP7)in breast cancer by bioinformatics.Methods R sofrware was used to explore the differential expression of the RBP7 gene in breast cancer by the cancer genome atlas(TCGA)dataset and the human protein atlas(HPA).Relationship between RBP7 and clinical data of breast cancer was evaluated by Kaplan-Meier survival analysis and receiver operating characteristic(ROC)curves.Correlation between high and low RBP7 expression groups and different tumor-infiltrating immune cells(TIICs)were analyzed based on the TCGA database.Gene set enrichment analysis(GSEA)was used to assess the distribute trends of RBP7 in gene tables sorted by phenotypic relatedness.Results RBP7 mRNA expression levels were down-regulated in breast cancer compared to paracancerous tissues,which were expressed in the nucleus.ROC curve analysis showed that the area under curve(AUC)of RBP7 for the diagnosis of breast cancer was 0.943(95%CI:0.926～0.960),and the best cut-off value of RBP7 was 6.29,with a sensitivity and specificity of 82.32%and 93.69%,respectively.Kaplan-Meier survival analysis showed that low expression of RBP7 was associated with overall survival rate in breast cancer patients(HR=0.68,95%CI:0.49～0.93,P=0.017),indicating that RBP7 was an independent risk factor for breast cancer.Spearman correlation showed that RBP7 was positively associated with pDC cells and NK cells(r=0.290,0.253,all P<0.05),and negatively associated with Th2 cells(r=-0.217,P<0.05)in breast cancer.GSEA showed that RBP7 was enriched in pathways such as adipogenesis,ribosome,peptiden ligand binding receptors,and calcium signaling pathway(all P<0.001).Conclusion RBP7 affects the occurrence and development of breast cancer,which may be a potential biomarker and therapeutic target for breast cancer.

Construction and Evaluation of the Disulfidptosis-Related Genes(DRGs)Prognostic Risk Model for Hepatocellular Carcinoma Based on TCGA Database / 现代检验医学杂志

Objective To construct and evaluate a disulfidptosis-related genes(DRGs)prognostic risk model for hepatocellular carcinoma(HCC)based on the cancer genome atlas(TCGA)database.Methods The expression of 15 DRGs in 371 HCC samples and 50 adjacent cancer samples in the TCGA database was analyzed using bioinformatics methods,and then gene ontology(GO)functional annotation,Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis and Kaplan-Meier(KM)survival analysis were performed.Statistical significant DRGs were screened through univariate COX regression analysis,and key DRGs were selected through LASSO regression analysis and multivariate COX regression analysis to construct a prognostic risk model.HCC patients were divided into high-risk and low-risk groups based on risk scores,and the KM survival curves and time-dependent receiver operator characteristic(ROC)curves were created to validate and evaluate prognostic risk models.Results Compared with the adjacent cancer samples,FLNA,MYH9,TLN1,ACTB,MYL6,CAPZB,DSTN,ACTN4,SLC7A11,INF2,CD2AP,PDLIM1,and FLNB were all upregulated in the 15 DRGs of HCC samples,and the differences were significant(t=1 793～6 310,all P<0.001).According to GO functional annotation and KEGG enrichment analysis,DRGs were closely related to biological processes or pathways related to actin cytoskeleton and cell adhesion.The results of KM survival analysis showed that the survival rate of the high expression group of SLC7A11,INF2,CD2AP,MYL6,and ACTB were lower than that of the low expression group[HR=1.46(1.03～2.07)～1.93(1.36～2.75),all P<0.05].Univariate COX regression analysis,LASSO analysis,and multivariate COX regression analysis were used to construct a prognostic risk model,with risk score=(0.247×SLC7A11)+(0.289×INF2)+(0.076×CD2AP)+(0.06×MYL6).The risk score of the sample in this model was calculated,and the higher the risk score,the more HCC patients with poor prognosis.KM survival analysis showed that the overall survival rate of the high-risk group was lower than that of the low-risk group.The AUC values for 1,3,and 5 years were 0.709,0.661,and 0.648,respectively.Multivariate COX regression analysis showed that SLC7A11[HR=1.832(1.274～2.636),P=0.001]was an independent prognostic risk factor.Conclusion The prognostic risk model was constructed by four DRGs,which has a certain role in predicting the prognosis of HCC patients.

Expression of optineurin in multiple myeloma and its clinical significance / 西安交通大学学报(医学版)

【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.

Development of a prognostic risk marker of colon adenocarcinoma based on a weighted gene co-expression network and its clinical significance / 中国比较医学杂志

Objective Because of the poor prognosis of colon adenocarcinoma(COAD),it is necessary to screen prognosis-related genes in COAD patients and establish a new prognostic risk assessment model.Methods COAD-related data from the cancer genome atlas(TCGA)and gene expression omnibus(GEO)were used as training and validation sets,respectively.Weighted gene co-expression network analysis(WGCNA),a Cox regression model and least absolute selection and shrinkage operator(LASSO)regression analysis were used to screen prognosis-related genes of COAD and establish a prognostic model.A receiver operating characteristic(ROC)curve was combined with a survival curve to verify the model accuracy,and a nomogram was constructed.Patients were divided into two groups by the median risk score.The immune cell proportion score(IPS)was used to evaluate the immunotherapy response of the two groups.Results A total of 15 feature genes were screened.The area under the ROC curve in the predictive model of COAD patients was＞0.6,and the survival rate of the high-risk group was significantly lower than that of the low-risk group(P＜0.05),suggesting a good distinguishing ability for high-and low-risk COAD patients.Patients in the low-risk group had a higher IPS(P=0.026),indicating a better response to immunotherapy.Conclusions The model developed for COAD in this study has a good ability to predict the survival of patients at high and low risk of COAD.

The expression of SCAMP3 in hepatocellular carcinoma and its prognostic analysis based on TCGA database / 中华肝胆外科杂志

Objective:To study the expression and prognostic impact of secretory carrier membrane protein 3 (SCAMP3) in hepatocellular carcinoma (HCC) and its gene set enrichment analysis.Methods:SCAMP3 expression and its prognosis were analyzed using The Cancer Genome Atlas (TCGA) database. The cancer tissue and paracancerous tissue were collected from four patients with HCC undergoing surgery in Lishui Central Hospital to detect the expression of SCAMP3. Based on TCGA database, univariate and multivariate Cox regression was performed to analyze the relevance of SCAMP3 with prognosis of HCC. Gene set enrichment analysis was utilized to clarify the biological role of SCAMP3.Results:In TCGA database, SCAMP3 expression was higher in HCC tissues than that in normal liver tissues ( Z=-8.38, P<0.001). Patients were divided into the low-expression group ( n=185) and high-expression group ( n=185) based on the median SCAMP3 expression, and the overall survival rate was lower in patients with high SCAMP3 expression. In our four patients. The expression of SCAMP3 mRNA and protein in cancer tissues was higher than that in paracancerous tissues ( t=8.55, 6.24, both P<0.001). In multivariate Cox regression analysis, the higher SCAMP3 expression was associated with a higher risk of death ( HR=1.466, 95% CI: 1.143-1.881, P<0.001). Gene set enrichment analysis in patients with high SCAMP3 expression, the coagulation cascade and three signaling pathways involving the complements, retinol metabolism, and peroxisome proliferator-activated receptor were identified. Conclusion:SCAMP3 expression elevated in HCC, patients with a higher expression of SCAMP3 might have a worse prognosis. High SCAMP3 expression is a risk factor for the survival of patients with HCC. High SCAMP3 expression is associated with the coagulation cascade and the complements, retinoid metabolism, and peroxisome proliferator-activated receptor pathways.

Correlation analysis between SLC52A2 gene expression and prognosis of patients with uveal melanoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the correlation between SLC52A2 and uveal melanoma(UM)based on the cancer genome atlas(TCGA)database, and preliminarily explore the influence of SLC52A2 on the prognosis of UM patients and potential mechanism.METHODS: The clinical information on 80 patients with UM and mRNA expression data of SLC52A2 were collected from TCGA database. According to the expression level of SLC52A2, 80 patients were divided into high and low expression groups by median method. The relationship between the expression of SLC52A2 and clinical pathological features, as well as the prognosis was analyzed. The age, sex, clinical stage, pathological stage, and mRNA expression of SLC52A2 were analyzed by univariate and multivariate Cox analysis to search the prognostic factors of UM. Enrichment analyses were used to predict the possible regulatory pathway of SLC52A2 in UM.RESULTS: The survival prognosis of patients with low expression of SLC52A2 was better than that of patients with high expression of SLC52A2(P&#x003C;0.05). The level of SLC52A2 has no significant correlation with the age, sex, clinical stage, and pathological stage of patients in both groups(P&#x003E;0.05). Multivariate Cox analysis showed that the high expression of SLC52A2 was a risk factor for poor prognosis. The nomogram prediction model developed by combining the expression of SLC52A2 with clinical pathological features could accurately predict the survival probability of UM patients. The infiltration abundance of Th2 and Treg cells in both groups has difference(all P&#x003C;0.001). GSEA analysis showed that the gene of JAK-STAT(FDR=0.028, P=0.004)and PI3K/AKT(FDR=0.017, P=0.002)were rich in samples with high expression of SLC52A2.CONCLUSION: The high expression of SLC52A2 is a risk factor for the prognosis of UM patients. SLC52A2 can be used as a biomarker to predict the prognosis and to become a new target for the treatment of patients with UM.

Role of miR-5010-3p in predicting the prognosis of hepatocellular carcinoma / 中南大学学报(医学版)

Objective:Numerous miRNAs have been found to be abnormally expressed in hepatocellular carcinoma(HCC).However,clinical significance of miR-5010-3p in HCC is not elucidated.This study aims to explore the prognostic value and role of miR-5010-3p in HCC.Methods:The differential gene expression analysis of miR-5010-3p in HCC was performed based on the Cancer Genome Atlas(TCGA)database.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of miR-5010-3p expression level for HCC prognosis.The Kaplan-Meier,Cox univariate,and Cox multivariate analysis were used to predict its role in the prognosis of HCC.The downstream target genes were predicted.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed to predict the potential functional pathways they may participate in.Finally,methyl thiazolyl tetrazolium(MTT)assay and 5-ethyl-2'-deoxyuridine(EDU)incorporation experiment were carried out to prove its effect on proliferation.Results:The expression of miR-5010-3p was associated with histological grade(P=0.019),vascular invasion degree(P=0.049),TP53 level(P=0.004),and alpha fetoprotein(AFP)level(P=0.012).A moderate ability to distinguish between tumor and paracancerous tissues of miR-5010-3p in HCC was perceived by ROC curve(AUC:0.712,95%CI 0.649 to 0.776).High expression of miR-5010-3p was associated with shorter overall survival(OS)(P=0.003).The results of functional enrichment analysis showed that miR-5010-3p was related to the tumorigenesis process.In vitro experiments verified that miR-5010-3p promoted the proliferation of hepatocellular carcinoma cells.Conclusion:MiR-5010-3p promotes the proliferation of liver cancer cells,and its high expression is associated with poor prognosis,which may be a potential prognostic marker.

Identification of diagnostic signatures associated with tumor mutation burden in gastric cancer based on TCGA and machine-learning methods / 西安交通大学学报(医学版)

【Objective】 To select and identify miRNA signatures to predict TMB level in gastric cancer based on The Cancer Genome Atlas (TCGA) database and machine learning methods. 【Methods】 MiRNA expression and somatic mutation profiles of gastric cancer (GC) were downloaded from TCGA database. R "limma" package was performed to select differentially expressed miRNAs between high-TMB and low-TMB groups. Two machine learning algorisms, random forest (RF), and Support Vector Machine-Recursive Feature Elimination were utilized to identify miRNAs with the highest discriminative ability. ROC was used to test the predictive ability of these signatures in multiple datasets. Besides, immune cells of different TMB levels were compared by the CIBERSORT method. 【Results】 A total of 56 differentially expressed miRNAs (DE-miRNAs) were filtered. Functional enrichment analysis showed that these DE miRNAs are mainly enriched in signaling pathways related to tumor occurrence and development as well as immunity-related biological processes. The RF and SVM-RFE algorithms jointly identified 10 diagnostic features of miRNAs, among which only hsa-miR-210-3p is considered the most relevant predictive biomarker for TMB classification. The AUC value of hsa-miR-210-3p in the training, testing, and total sets is 0.822, 0.721, and 0.793, respectively, and has been validated in other cancer types. Besides, CIBERSORT analysis suggests differences in immune cell infiltration between high- and low-TMB groups. Meanwhile, there is a significant positive correlation between the expression of immune checkpoint related genes and mismatch repair related genes and hsa-miR-210-3p. 【Conclusion】 This study successfully identified hsa-miR-210-3p as a predictive biomarker for TMB classification, which can effectively predict TMB values in gastric cancer and other cancer patients and may provide some guidance for immunotherapy.

Expression and clinical significance of CC motif chemokine ligand 20 in esophageal carcinoma based on the Cancer Genome Atlas data mining / 解剖学报

Objective To explore the expression and significance of CC mokif chemokine ligand 20(CCL20) gene in esophageal carcinoma and its influence on the progression and prognosis of the disease. Methods The expression data of esophageal cancer were obtained from the Cancer Genome Atlas (TCGA) database, and were collected from cBioPortal(www.cbioportal.org).The survival curve was analyzed by Kaplan-Meier method. Through the website (http://ualcan.path.uab. edu) the objective was to analyze the expression of CCL20 gene in esophageal cancer tissues, the relationship between CCL20 and obesity and the methylation level of CCL20 in esophageal cancer. cBioPortal was used to analyze the copy number and mRNA expression of CCL20 gene. Finally, the expression differences of CCL20 in esophageal cancer tissues and adjacent tissues were analyzed by mRNA and protein levels. Results CCL20 was highly expressed in esophageal cancer, especially adenocarcinoma. The survival rate of patients with high expression of CCL20 was reduced. The expression of CCL20 was directly proportional to the degree of obesity in patients with esophageal cancer and inversely proportional to the degree of methylation. The expression of CCL20 in esophageal cancer tissues increased significantly. Conclusion CCL20 gene expression level is associated with poor prognosis of esophageal cancer patients.

Mitochondrial Fission Protein 1 (FIS1) Overexpression in Human Cervical Cancer Cells Promotes Mitochondrial Fission and Reduces Cell Proliferation and Migration Capacity / 中国生物化学与分子生物学报

Mitochondria are dynamic organelles that continuously divide and fuse. In recent years, in addition to the studies related to mitochondrial metabolism, the unique dynamics of mitochondria have gradually attracted researchers' attention. A growing body of research has revealed that mitochondrial dynamics are related to the biological behavior of tumor cells. Mitochondrial fission proteins (mitochondrial fission protein 1, FIS1) mediate the assembly of mitochondrial fission complexes and participate in the execution of mitochondrial fission. They are important proteins in the process of mitochondrial fusion and fission. However, few studies have revealed the expression and role of FIS1 in human cervical cancer. In this study, the expression level of FIS1 in human cervical cancer tissues and paracancer tissues were compared. The results showed that the level of FIS1 mRNA in human cervical cancer tissues was significantly lower than that in paracancer tissues (P<0. 01). Further KEGG pathway and GO Term-BP pathway analysis showed that the differential genes are mainly related to mitochondrial biological functions. Subsequently, HeLa cells with overexpressed FIS1 were investigated for their proliferation, migration, mitochondrial fission and ROS levels. The experimental results showed that FIS1 overexpression decreased HeLa cell proliferation and migration ability, enhanced mitochondrial fission and higher ROS levels. In conclusion, the expression of FIS1 in human cervical cancer cells was attenuated, while overexpression of FIS1 resulted in a series of abnormal biological functions in human cervical cancer cells. Further studies can be carried out to investigate the role of FIS1 in the treatment of human cervical cancer.

Expression and relevant bioinformatics analysis of miR-135b-5p in oral squamous cell carcinoma / 口腔疾病防治

Objective @# To observe the clinical significance of miR-135b-5p in oral squamous cell carcinoma (OSCC) tissues and to conduct a bioinformatics analysis of its predicted target genes.@*Methods @#The expression levels of miR-135b-5p in OSCC tissues and adjacent normal tissues were compared using data from TCGA and GEO databases, and the correlations of miR-135b-5p expression level with clinicopathologic characteristics were analyzed. Fresh tissues were collected in the clinic, and the expression of miR-135b-5p was verified by quantitative real-time PCR. The target genes with enriched pathways were analyzed by using bioinformatics methods. A protein-protein interaction network was constructed to screen hub genes.@*Results @#The expression levels of miR-135b-5p were significantly upregulated in OSCC tissues compared to adjacent normal tissues (P < 0.001) and had a good diagnostic capability (AUC=0.960, P < 0.001). The expression level of miR-135b-5p was positively correlated with histopathological grading (P=0.011). Enrichment analyses revealed that the target genes of miR-135b-5p were significantly associated with tumor-related signaling pathways, such as the calcium signaling pathway, the cGMP-PKG signaling pathway and the cAMP signaling pathway. Ten core target genes were obtained by screening: DLG2, ANK3, ERBB4, SCN2B, NBEA, GABRB2, ATP2B2, SNTA1, CACNA1D, and SPTBN4.@*Conclusion@#miR-135b-5p may act as an oncogene miRNA in OSCC and has the potential value of acting as a diagnostic biomarker and therapeutic target for OSCC.

Acetyl-CoA Carboxylase 1 (ACC1) Affects the Proliferation of Clear Cell Renal Cell Carcinoma (ccRCC) by Regulating Cyclin D1/CDK4 / 中国生物化学与分子生物学报

Acetyl-CoA carboxylase (ACC) is the rate limiting enzyme of fatty acid synthesis pathway. Studies have shown that ACC1 is implicated in a variety of metabolic diseases and cancer. However, the role and mechanism of action of ACC1 in clear cell renal cell carcinoma (ccRCC) have not been reported. In this study, 786-O and Caki-1 clear cell renal carcinoma cells were used as research objects to investigate the effect of abnormal expression of ACC1 on their proliferation and unravel the underlying mechanism. Red oil-O-staining results showed that the lipid content of 786-O and Caki-1 cells was significantly higher than that of human kidney 2 (HK2) cells. By searching TCGA database, we found that the expression of ACC1 proteins in ccRCC was significantly higher than that in normal renal tissues (P < 0.001). Plus, ACC1 protein expression in all clinical TNM stages was significantly higher than that in normal tissues, and the higher the expression of ACC1, the higher the pathological grade. Furthermore, high expression of ACC1 mRNA is positively correlated with poor prognosis in ccRCC patients. Western blotting analysis showed that the expression of ACC1 in 786-O and Caki-1 cells was significantly higher than that in HK2 cells. The results of red oil-O-staining showed that knocking down ACC1 could significantly reduce the lipid content of 786-O and Caki-1 cells. The results of CCK-8 assays and clonogenicity analysis showed that knocking down ACC1 could significantly reduce the proliferation and colony forming ability of 786-O and Caki-1 cells. Flow cytometry analysis showed that after knocking down ACC1, the cell cycle was blocked at the G

Bioinformatics Analysis and Preliminary Functional Study of Abnormal Expression of Splicing Factors in Gastric Cancer / 中国医学科学院学报

To analyze the expression of splicing factors in gastric cancer using bioinformatics methods and investigate the effect of aberrantly expressed serine/arginine-rich splicing factor(SRSF10)on the phenotype of gastric cancer cells. The RNA-seq data of gastric cancer and paracancerous tissues were downloaded from The Cancer Genome Atlas(TCGA)cancer database,and bioinformatics analysis was performed to obtain the splicing factors differentially expressed in gastric cancer.The splicing factor SRSF10 was selected to investigate its effect on the development of gastric cancer.RNA interference technology was used to construct SRSF10 knockdown gastric cancer cells.MTS,Transwell,and cell scratches were used to study the effect of SRSF10 knockdown on gastric cancer cell phenotype. A total of 48 splicing factors were identified in gastric cancer by a series of bioinformatics techniques,of which 35 were up-regulated and 13 were down-regulated.The splicing factor SRSF10,which was up-regulated,was selected for further study.It was found that the gastric cancer cells after SRSF10 knockdown proliferated more slowly and had lower migration ability than normal gastric cancer cells. Multiple splicing factors are found in gastric cancer and may play an important role in the development of gastric cancer.The splicing factor SRSF10 may contribute to the pathogenesis of gastric cancer.

MicroRNA model that can predict the prognosis of oral squamous cell carcinoma based on bioinformatics analysis / 华西口腔医学杂志

OBJECTIVE@#The microRNA (miRNA) prognostic model can predict the prognosis of patients with oral squamous cell carcinoma (OSCC) on the basis of bioinformatics. Moreover, it can accurately group OSCC patients to improve targeted treatment.@*METHODS@#We downloaded the miRNA and mRNA expression profile and clinical data of OSCC from The Cancer Genome Atlas (TCGA). The risk score model of miRNA was screened and established by univariate and multivariate Cox regression models. The performance of this prognostic model was tested by receiver operating characteristic (ROC) curves and area under the curve (AUC). The target genes of six miRNAs were predicted and intersected with differential mRNA for enrichment analysis by Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and gene ontology (GO) enrichment analysis. A protein protein interaction network (PPI) was constructed to screen hub genes.@*RESULTS@#By using univariate and multivariate Cox regression analyses, the prognostic risk model was obtained. The AUC of the ROC curve for predicting 5-year survival in the training group, test group, and whole cohort were 0.757, 0.673, and 0.724, respectively. Furthermore, univariate Cox regression and multivariate Cox regression considering other clinical factors showed that the six-miRNAs signature could serve as an independent prognostic factor (P<0.001). The top 10 hub genes in the PPI network screened by intersecting target genes include CCNB1, EGF, KIF23, MCM10, ITGAV, MELK, PLK4, ADCY2, CENPF, and TRIP13. EGF and ADCY2 were associated with survival prognosis (P<0.05).@*CONCLUSIONS@#The six-miRNAs signature could efficiently function as a novel and independent prognostic model for OSCC patients, which may be a new method to guide the accurate targeting treatment of OSCC.

Prognostication of uveal melanoma is simple and highly predictive using The Cancer Genome Atlas (TCGA) classification: A review

Purpose: The cancer genome atlas (TCGA) is a comprehensive project supported by the National Cancer Institute (NCI) in the United States to explore molecular alterations in cancer, including uveal melanoma (UM). This led to TCGA classification for UM. In this report, we review the American Joint Committee on Cancer (AJCC) classification and TCGA classification for UM from the NCI's Center for Cancer Genomics (NCI CCG) (based on enucleation specimens [n = 80 eyes]) and from Wills Eye Hospital (WEH) (based on fine needle aspiration biopsy [FNAB] specimens [n = 658 eyes]). We then compare accuracy and predictability of AJCC versus (vs.) TCGA. Methods: Review of published reports on AJCC and TCGA classification for UM was performed. Outcomes based on AJCC 7th and 8th editions were assessed. For TCGA, UM was classified based on chromosomes 3 and 8 findings including disomy 3 (D3), monosomy 3 (M3), disomy 8 (D8), 8q gain (8qG), or 8q gain multiple (8qGm) and combined into four classes including Class A (D3/D8), Class B (D3/8qG), Class C (M3/8qG), and Class D (M3/8qGm). Outcomes of metastasis and death were explored and a comparison (AJCC vs. TCGA) was performed. Results: In the NCI CCG study, there were 80 eyes with UM sampled by enucleation (n = 77), resection (n = 2), or orbitotomy (n = 1) and analysis revealed four distinct genetic classes. Metastasis and death outcomes were subsequently evaluated per class in the WEH study. The WEH study reviewed 658 eyes with UM, sampled by FNAB, and found Class A (n = 342, 52%), B (n = 91, 14%), C (n = 118, 18%), and D (n = 107, 16%). Comparison by increasing class (A vs. B vs. C vs. D) revealed older mean patient age (P < 0.001), worse entering visual acuity (P < 0.001), greater distance from the optic disc (P < 0.001), larger tumor diameter (P < 0.001), and greater tumor thickness (P < 0.001). Regarding outcomes, more advanced TCGA class demonstrated increased 5-year risk for metastasis (4% vs. 20% vs. 33% vs. 63%,P < 0.001) with corresponding increasing hazard ratio (HR) (1.0 vs. 4.1, 10.1, 30.0,P= 0.01 for B vs. A andP < 0.001 for C vs. A and D vs. A) as well as increased 5-year estimated risk for death (1% vs. 0% vs. 9% vs. 23%,P < 0.001) with corresponding increasing HR (1 vs. NA vs. 3.1 vs. 13.7,P= 0.11 for C vs. A andP < 0.001 for D vs. A). Comparison of AJCC to TCGA classification revealed TCGA was superior in prediction of metastasis and death from UM. Conclusion: TCGA classification for UM is simple, accurate, and highly predictive of melanoma-related metastasis and death, more so than the AJCC classification.

Expression and clinical significance of UBE2T in primary liver cancer / 实用肿瘤学杂志

Objective The objective of this study was to analyze the expression of ubiquitin -conjugating enzyme E2T (UBE2T)in primary liver cancer and its relationship with clinicopathological parameters and prognosis of patients with liver cancer. Methods The second generation sequencing data and clinical pathological data of UBE2T gene mRNA in normal liver tissues and liver cancer tissues were downloaded from the Cancer Genome Atlas(TCGA)database. The expression of UBE2T in cancer tissues and normal tissues was analyzed to elucidate the relationship between UBE2T at mRNA level and clinicopathological parameters of patients with liver cancer. Kaplan-Meier was used for prognostic analysis. The Cox proportional hazard regression model was performed for the multivariate analysis of the prognostic factors associated with HCC. Based on the results of gene set enrichment analysis(GSEA), UBE2T was involved in the possible regulating pathways of HCC development. Results The expression of UBE2T at mRNA level in hepatocarcinoma tissues was significantly higher than that in adjacent tissues(P<0. 01). The high expression of UBE2T was closely related to pathological grade,TNM staging,and vascular invasion(P<0. 01),suggesting a poor prognosis of patients with liver cancer. Multivariate Cox regression analysis showed that TNM staging,vascular invasion and UBE2T expression were independent risk factors affecting the prognosis of patients with liver cancer. Conclusion The high expression of UBE2T is significantly associated with the clinicopathological factors and prognosis of patients with liver cancer. It can be used as a potential marker for predicting the prognosis of liver cancer patients and a target for tumor therapy.

Radiomics MRI Phenotyping with Machine Learning to Predict the Grade of Lower-Grade Gliomas: A Study Focused on Nonenhancing Tumors

OBJECTIVE: To assess whether radiomics features derived from multiparametric MRI can predict the tumor grade of lower-grade gliomas (LGGs; World Health Organization grade II and grade III) and the nonenhancing LGG subgroup. MATERIALS AND METHODS: Two-hundred four patients with LGGs from our institutional cohort were allocated to training (n = 136) and test (n = 68) sets. Postcontrast T1-weighted images, T2-weighted images, and fluid-attenuated inversion recovery images were analyzed to extract 250 radiomics features. Various machine learning classifiers were trained using the radiomics features to predict the glioma grade. The trained classifiers were internally validated on the institutional test set and externally validated on a separate cohort (n = 99) from The Cancer Genome Atlas (TCGA). Classifier performance was assessed by determining the area under the curve (AUC) from receiver operating characteristic curve analysis. An identical process was performed in the nonenhancing LGG subgroup (institutional training set, n = 73; institutional test set, n = 37; and TCGA cohort, n = 37) to predict the glioma grade. RESULTS: The performance of the best classifier was good in the internal validation set (AUC, 0.85) and fair in the external validation set (AUC, 0.72) to predict the LGG grade. For the nonenhancing LGG subgroup, the performance of the best classifier was good in the internal validation set (AUC, 0.82), but poor in the external validation set (AUC, 0.68). CONCLUSION: Radiomics feature-based classifiers may be useful to predict LGG grades. However, radiomics classifiers may have a limited value when applied to the nonenhancing LGG subgroup in a TCGA cohort.

von Willebrand Factor Gene Expression in Primary Lower Grade Glioma: Mutually Co-Occurring Mutations in von Willebrand Factor, ATRX, and TP53

BACKGROUND: Venous thromboembolism is a common complication in patients with glioma. The clotting factor von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. In the current analysis, we examined The Cancer Genome Atlas (TCGA) data to assess the VWF gene in patients with lower grade gliomas. METHODS: For newly diagnosed gliomas, we evaluated the association between VWF and overall survival in the Genomic Data Commons TCGA Lower Grade Glioma (LGG) dataset in TCGA. Simple statistics were calculated to identify patterns of mutual exclusivity or co-occurrence of VWF mutations. For each pair of query genes an odds ratio was calculated that indicates the likelihood that the mutations in the two genes are mutually exclusive or co-occurrent across the selected cases. To determine whether the identified relationship was significant for a gene pair, Fisher's exact test was performed. RESULTS: Lower grade gliomas with less VWF gene expression had significantly better survival than those with more VWF gene expression (hazard ratio 0.64, 95% confidence interval 0.44 to 0.92, p=0.015 log rank test). When we analyzed the data with Cox regression, VWF expression had a significant effect on survival (p=0.02) that was unrelated to the effect of IDH1 expression (p=0.062), TP53 expression (p=0.135), independent of ATRX expression (p=0.021) and histology (astrocytoma versus oligoastrocytoma and oligodendroglioma, p=0.002). VWF mutations significantly co-occur with mutations in TP53 and ATRX (p<0.001). CONCLUSION: The deleterious prognostic effect of VWF expression and its co-occurrent mutations with TP53 and ATRX in lower grade gliomas are not surprising, given VWF's role in other cancers. Therefore, VWF gene expression may be a clinically important risk marker in lower grade glioma.

Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma / 生物医学工程学杂志

To evaluate the differential expression profiles of the lncRNAs, miRNAs, mRNAs and ceRNAs, and their implication in the prognosis in clear cell renal cell carcinoma (CCRCC), the large sample genomics analysis technologies were used in this study. The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas (TCGA) database, and R software was used for gene expression analysis and survival analysis. Cytoscape software was used to construct the ceRNA network. The results showed that a total of 1 570 lncRNAs, 54 miRNAs, and 17 mRNAs were differentially expressed in CCRCC, and most of their expression levels were up-regulated (false discovery rate 2). The ceRNA regulatory network showed the interaction between 89 differentially expressed lncRNAs and 9 differentially expressed miRNAs. Further survival analysis revealed that 38 lncRNAs (including COL18A1-AS1, TCL6, LINC00475, UCA1, WT1-AS, HOTTIP, PVT1, etc.) and 2 miRNAs (including miR-21 and miR-155) were correlated with the overall survival time of CCRCC ( < 0.05). Together, this study provided us several new evidences for the targeted therapy and prognosis assessment of CCRCC.