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Objective·To establish a prognostic model for the overall survival (OS) of hepatocellular carcinoma (HCC) based on mitochondrial genes and clinical information.Methods·The gene expression and the clinical data of 369 HCC patients and 50 controls with normal liver were downloaded from The Cancer Genome Atlas (TCGA) database. The nuclear-encoded mitochondrial genes (NEMGs) were obtained from the MitoCarta3.0 database. The "DESeq2" R package and univariate Cox analysis were used to select NEMGs [ubiquinol cytochrome C reductase hinge protein (UQCRH), ATP citrate lyase (ACLY), phosphoenolpyruvate carboxykinase 2 (PCK2), Bcl-2 homologous antagonist/killer1 (BAK1), Bcl-2-associated X protein (BAX) and Bcl-2/adenovirus E1B interacting protein 3-like (BNIP3L)] in HCC that were associated with OS of HCC and participated in dysregulation of oxidative phosphorylation, tricarboxylic acid cycle and cell apoptosis. Multivariate Cox analysis was applied to select independent risk factors for OS of HCC. A comprehensive prognostic model and a prognostic nomogram with 6-NEMG risk characteristics and TNM staging were established. By using the median of prognostic scores as a cut-off, HCC patients were classified into low-risk and high-risk group. Kaplan-Meier survival curve analysis was conducted and log-rank test was performed to evaluate the survival rates between the low-risk and high-risk group. The area under the curve (AUC) values of receiver operating characteristic (ROC) curve were calculated via using the "timeROC" package. The prognostic model for HCC was validated by using the GEO HCC cohort (GSE14520) for 1, 3 and 5 years. Finally, the relative expression level of 6-NEMG was validated in 34 clinical samples of HCC from Xinhua Hospital, Shanghai Jiao Tong University School of Medicine by using real-time quantitative polymerase chain reaction (qPCR) method.Results·Compared to 6-NEMG risk signature only (AUCs for 1, 3 and 5 years were 0.77, 0.66 and 0.65, respectively) or TNM stage only (AUCs for 1, 3 and 5 years were 0.66, 0.67 and 0.63, respectively), ROC curve analysis showed that this integrated prognostic model displayed better predictive performance for 1-year (AUC, 0.78), 3-year (AUC, 0.73) and 5-year (AUC, 0.69) OS of HCC. The Kaplan-Meier survival curve analysis showed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group (P=0.001). In addition, predictive performance of the prognostic model (AUC for 1, 3 and 5 years is 0.67, 0.66 and 0.74, respectively) and prognostic differences between the high-risk and low-risk group (P=0.001) were further validated in GEO (GSE14520) external cohort, and these results were consistent with the TCGA data. In addition to BNIP3L, dysregulation of five other NEMGs in the clinical HCC cohort was validated. The correlation analysis in GSE14520 and HCC clinical cohort showed a positive correlation between prognosis score and the size and number of tumors.Conclusion·A new prognostic model that combines 6-NEMG risk characteristics with TNM staging for predicting OS in HCC patients was constructed and validated. This model may help improve the prognosis prediction of HCC patients.

Objective: To explore the relationship between CD1c gene expression and prognosis in breast cancer (BRCA) through TCGA database and GEO database. Methods: GEPIA, Kaplan-Meier Plotter and R software were used to comprehensively analyze and verify the function and role of CD1c. Expression level of CD1c in BRCA was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Results: Compared with normal breast tissue, CD1c was lowly expressed in BRCA tissue. Kaplan-Meier survival analysis of samples from multiple datasets showed that patients in CD1c low expression group had a significantly worse overall prognosis. Immune correlation analysis revealed that CD1c had strong correlation with immature iDC cells, T cells, DC cells and B cells. The results of qRT-PCR showed that expression of CD1c was lower in BRCA tissues than in paired paracancer tissues (P<0.01) . IHC results showed that high CD1c expression was associated with longer PFS in patients (P=0.024). Conclusion: Low expression of CD1c is significantly correlated with the poor prognosis of BRCA patients, and its expression is closely related to immune infiltration, which may provide new help for the immunotherapy of BRCA patients. [ABSTRACT FROM AUTHOR]

Objective·To establish a prognostic model for the overall survival (OS) of hepatocellular carcinoma (HCC) based on mitochondrial genes and clinical information. Methods·The gene expression and the clinical data of 369 HCC patients and 50 controls with normal liver were downloaded from The Cancer Genome Atlas (TCGA) database. The nuclear-encoded mitochondrial genes (NEMGs) were obtained from the MitoCarta3.0 database. The "DESeq2" R package and univariate Cox analysis were used to select NEMGs [ubiquinol cytochrome C reductase hinge protein (UQCRH), ATP citrate lyase (ACLY), phosphoenolpyruvate carboxykinase 2 (PCK2), Bcl-2 homologous antagonist/killer1 (BAK1), Bcl-2-associated X protein (BAX) and Bcl-2/adenovirus E1B interacting protein 3-like (BNIP3L)] in HCC that were associated with OS of HCC and participated in dysregulation of oxidative phosphorylation, tricarboxylic acid cycle and cell apoptosis. Multivariate Cox analysis was applied to select independent risk factors for OS of HCC. A comprehensive prognostic model and a prognostic nomogram with 6-NEMG risk characteristics and TNM staging were established. By using the median of prognostic scores as a cut-off, HCC patients were classified into low-risk and high-risk group. Kaplan-Meier survival curve analysis was conducted and log-rank test was performed to evaluate the survival rates between the lowrisk and high-risk group. The area under the curve (AUC) values of receiver operating characteristic (ROC) curve were calculated via using the "timeROC" package. The prognostic model for HCC was validated by using the GEO HCC cohort (GSE14520) for 1, 3 and 5 years. Finally, the relative expression level of 6-NEMG was validated in 34 clinical samples of HCC from Xinhua Hospital, Shanghai Jiao Tong University School of Medicine by using real-time quantitative polymerase chain reaction (qPCR) method. Results·Compared to 6-NEMG risk signature only (AUCs for 1, 3 and 5 years were 0.77, 0.66 and 0.65, respectively) or TNM stage only (AUCs for 1, 3 and 5 years were 0.66, 0.67 and 0.63, respectively), ROC curve analysis showed that this integrated prognostic model displayed better predictive performance for 1-year (AUC, 0.78), 3-year (AUC, 0.73) and 5-year (AUC, 0.69) OS of HCC. The Kaplan-Meier survival curve analysis showed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group (P=0.001). In addition, predictive performance of the prognostic model (AUC for 1, 3 and 5 years is 0.67, 0.66 and 0.74, respectively) and prognostic differences between the high-risk and low-risk group (P=0.001) were further validated in GEO (GSE14520) external cohort, and these results were consistent with the TCGA data. In addition to BNIP3L, dysregulation of five other NEMGs in the clinical HCC cohort was validated. The correlation analysis in GSE14520 and HCC clinical cohort showed a positive correlation between prognosis score and the size and number of tumors. Conclusion·A new prognostic model that combines 6-NEMG risk characteristics with TNM staging for predicting OS in HCC patients was constructed and validated. This model may help improve the prognosis prediction of HCC patients. [ABSTRACT FROM AUTHOR]

Copyright of Journal Of Sichuan University (Natural Sciences Division) / Sichuan Daxue Xuebao-Ziran Kexueban is the property of Editorial Department of Journal of Sichuan University Natural Science Edition and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Shenyang Pharmaceutical University is the property of Shenyang Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the expression level and clinical significance of ALDH5A1 in ovarian cancer (OC) tissues, as well as to explore the possible mechanism associated with the invasion and migration of OC cells. Methods We initially compared ALDH5A1 expression in metastatic tissues and the primary site of OC based on the GEO database. Then, wound-healing and Transwell assays were utilized to determine the biological role of OC cells transfected with ALDH5A1 siRNA. To unravel the potential mechanism of ALDH5A1 meditating the metastasis of OC, the coexpression profile of ALDH5A1 in OC cell lines and OC patients were generated using cBioPortal. Moreover, the TCGA and GEO databases were used to analyze the relationship between ALDH5A1 expression and the prognosis of OC patients. The HPA database was further used to confirm the relative expression of ALDH5A1 and MMPs in OC patients. Results ALDH5A1 expression was downregulated in metastatic tissues compared with the primary site of OC, and ALDH5A1 knockdown promoted the malignant behavior of OC cells. Additionally, the coexpression profile of ALDH5A1 was significantly enriched in the extracellular matrix (ECM) organization pathway. Western blot assay further confirmed that the expression of MMP, which played an important role in the ECM pathway, was negatively correlated with ALDH5A1 expression in OC. These results indicated that ALDH5A1 may participate in the metastasis and invasion of OC via the ECM organization pathway. Finally, KM survival plots revealed that the survival rates of OC patients with lower ALDH5A1 expression were obviously lower. Conclusion ALDH5A1 downregulation may promote the tumor metastasis and contribute to poor prognosis in OC.

Objective: To investigate the mechanism and clinical value of zinc finger protein 492 (ZNF492) gene mutation in ovarian cancer, and to provide a theoretical basis for the diagnosis and treatment of ovarian cancer. Methods: The transcriptome data of ZNF492 mutant samples were downloaded by TCGA, and the samples were divided into two groups: ZNF492 mutant and non-mutant groups. The R package DESeq2 was used to analyze the differential genes between the two groups. The differentially expressed genes were analyzed by kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and gene set enrichment analysis (GSEA). The age, tumor stage and differentiation of ovarian cancer patients were obtained, and the Nomogram model was constructed and evaluated by multivariate COX regression prediction model of ZNF492 expression and clinical characteristics of ovarian cancer patients. Results: There were 100 up -regulated genes and 971 down-regulated genes in the differential genes between the ZNF492 mutant group (n=377) and the non-mutant group (n=2). The pathway enrichment analysis of differential genes between the two groups and 100 up-regulated genes in the ZNF492 mutant group showed that they were enriched transforming growth factor -β (TGF -β) signal path. The results of multivariate COX regression prediction model showed that higher age (≥65 years old), the higher tumor stage (Ⅲ-Ⅳ stage) and differentiation (G3) might be related to the poor overall survival (HR>1), while high expression of ZNF492 (≥0.672) was related to the better prognosis (HR＜1), among which the higher age patients (≥65 years old) had a poor prognosis (P＜0.01). Based on the above four factors, further construct the Nomogram prediction model. The model validation results showed that the C index was 0.593, the area under the curve (AUC) (0.610 and 0.566) of three-year and five-year ROC curves, and the clinical decision curve analysis (DCA) suggested that patients can take bold measures when the 3-year or 5-year survival rate was greater than 18% and less than 82% . Conclusions: Mutated ZNF492 may affect the occurrence and development of ovarian cancer by regulating TGF -β pathway and anti -apoptosis potential mechanism, and has strong clinical practical value in predicting prognosis. ZNF492 mutation is expected to be a marker of circulating tumour DNA and therapeutic target for ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective To identify the potential prognostic biomarkers of the immune-related genes signature for patients with hepatocellular carcinoma (HCC). Methods Original HCC data were downloaded from TCGA, and the immune activity of each sample was calculated by ssGSEA. HCC samples were divided into high and low immune cell infiltration groups by "GSVA" package and "hclust" package. The ESTIMATE algorithm scored the tumor microenvironment in each HCC sample. The "limma" package and Venn diagram identified effective immune-related genes. Univariate Cox, Lasso regression and multivariate Cox regression analyses were used to explore key genes. The "rms" package was used to create nomograms and draw calibration curves. Results Compared with the high immune cell infiltration group, the tumor purity of the samples in the low immune cell infiltration group was higher, the immune score, ESTIMATE score and stromal score were lower. In the high immune cell infiltration group, the immune components were more abundant, and the expression levels of TIGIT, PD-L1, PD-1, LAG3, TIM-3, CTLA4 and HLA family were higher. Multivariate Cox regression analysis showed that four immune-related genes (S100A9, HMOX1, IL18RAP and FCER1G) were used to construct the prognosis model. Compared with other clinical features, the risk score of this prognostic model was recognized as an independent prognostic factor. Conclusion This study identified the immune-related core genes which may be used in targeted therapy and immunotherapy of HCC.

Objective To investigate the expression level and clinical significance of ALDH5A1 in ovarian cancer (OC) tissues, as well as to explore the possible mechanism associated with the invasion and migration of OC cells. Methods We initially compared ALDH5A1 expression in metastatic tissues and the primary site of OC based on the GEO database. Then, wound-healing and Transwell assays were utilized to determine the biological role of OC cells transfected with ALDH5A1 siRNA. To unravel the potential mechanism of ALDH5A1 meditating the metastasis of OC, the coexpression profile of ALDH5A1 in OC cell lines and OC patients were generated using cBioPortal. Moreover, the TCGA and GEO databases were used to analyze the relationship between ALDH5A1 expression and the prognosis of OC patients. The HPA database was further used to confirm the relative expression of ALDH5A1 and MMPs in OC patients. Results ALDH5A1 expression was downregulated in metastatic tissues compared with the primary site of OC, and ALDH5A1 knockdown promoted the malignant behavior of OC cells. Additionally, the coexpression profile of ALDH5A1 was significantly enriched in the extracellular matrix (ECM) organization pathway. Western blot assay further confirmed that the expression of MMP, which played an important role in the ECM pathway, was negatively correlated with ALDH5A1 expression in OC. These results indicated that ALDH5A1 may participate in the metastasis and invasion of OC via the ECM organization pathway. Finally, KM survival plots revealed that the survival rates of OC patients with lower ALDH5A1 expression were obviously lower. Conclusion ALDH5A1 downregulation may promote the tumor metastasis and contribute to poor prognosis in OC. [ABSTRACT FROM AUTHOR]

To investigate the expression m1d significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas ( TCGA) database and tissue genotypic expression database ( GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue ( 3.05 0.72 vs. 0.33±0.16, P= 0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect (P<0.05). Survival analysis showed that the progression free survival time (P=0.033) and overall survival time (P=0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival ( P<0.05). The progression-free survival (P= 0.016) and overall survival (P=0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival (P <0.05). Based on Gene Ontology ( GO ) and Kyoto Encyclopedia of Genes and Genomes ( KEGG ), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis ( GSEA) showed that the Wnt/(3-catenin signaling pathway (P=0.023), the MAPK signaling pathway (P = 0.029) and glycolysis related pathway (P = 0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/B-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis. [ABSTRACT FROM AUTHOR]

构建基于肿瘤基因组图谱（TCGA）数据库胶质母细胞瘤（GBM）患者预后铁死亡基因相关lncRNA预 测模型。方法 通过TCGA数据库获取GBM的高通量测序数据，通过文献检索和搜查FerrDb数据库两种方式获取铁 死亡基因，并基于GBM中铁死亡相关差异表达的lncRNA构建GBM预后的多lncRNA模型，分析预后lncRNA与铁死 亡基因的共表达关系。结果 共获得与GBM相关的铁死亡基因246个，铁死亡相关lncRNA 2 624个，经差异分析和 降维处理，最终得到102个与GBM显著相关的铁死亡基因，并构建了一个包含111个lncRNA的GBM预后模型，其中，69 个差异有统计学意义的铁死亡基因与73个GBM预后相关的铁死亡lncRNA之间存在共表达关系。Kaplan-Meier生存 曲线显示，在预后模型下，高危者和低危者的总生存率差异有统计学意义（P<0. 01）。结论 基于TCGA数据库成功构 建GBM患者预后铁死亡基因相关lncRNA预测模型，该模型可在一定程度上预测GBM患者的生存率. [ABSTRACT FROM AUTHOR]

Objective To construct a prognostic model of laryngeal cancer based on pyroptosis-related lncRNAs. Methods Transcriptome expression and clinical data of patients with laryngeal cancer were downloaded from TCGA database. Differentially-expressed pyroptosis-related lncRNAs were selected using Wilcox rank sum test and Spearman correlation analysis. LncRNAs associated with patients' prognosis were further selected using univariate Cox analysis (P < 0.05), and a prognostic model was established using multivariate Cox regression. ROC curve was used to assess the sensitivity and specificity of this model. Results There were a total of 483 differentially-expressed pyroptosis-related lncRNAs in laryngeal cancer tissues, compared with normal laryngeal tissues (|logFC|≥1, FDR < 0.05). Univariate Cox analysis showed that 23 differentially-expressed lncRNAs were associated with prognosis. Multivariate Cox regression analysis finally obtained a prognostic model based on 10 lncRNAs for predicting the survival of laryngeal carcinoma patients. AUC showed that the model had a good predictive ability (AUC > 0.8). Conclusion Pyroptosis-related lncRNAs can be used to predict the prognosis of patients with laryngeal cancer.

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To study the relationship and significance of CLEC16A gene and the development and prognosis of mixed renal carcinoma (KIPAN) based on data mining.Methods The CLEC16A gene expression profile of KIPAN and its clinical information were downloaded from the TCGA database.The Perl script and R package were used to process the data and analyze the relationship. Results The expression of CLEC16A in KIPAN was lower than that in normal tissues,and with the improvement of KIPAN clinical grade, the expression of CLEC16A showed a downward trend.Low CLEC16A expression was positively correlated with poor prognosis in KIPAN (overall survival HR =0.69, P =0.006; disease-free survival: HR = 0.72, P =0.028). The results of gene set enrichment analysis showed that the high expression of CLEC16A was mainly enriched in biological processes or pathways such as lysosome and oxidative phosphorylation.The low expression of CLEC16A was enriched in signaling pathways such as antigen processing and presentation, production of IGA intestinal immune network, leukocyte trans endothelial migration, NOD-like receptor signaling pathway, and natural killer cell-mediated cytotoxicity. Conclusion CLEC16A may act as an inhibitor of the occurrence of KIPAN, its low expression is a risk factor for the progression and poor prognosis of renal cancer, and its high expression may be a protective factor against the occurrence of KIPAN. [ABSTRACT FROM AUTHOR]

Objective To investigate the application value of the human B cell-confinement receptor P2RY8 in the diagnosis and prognosis of hepatocellular carcinoma (HCC) and its association with tumor immunity. Methods The Cancer Genome Atlas database was used to compare the expression of P2RY8. R software package was used to analyze the correlation between P2RY8 and tumor staging, and the receiver operating characteristic (ROC) curve and a nomogram model were established for diagnosis and survival. Tumor Immune Evaluation Resource was used to analyze immune cell infiltration, immune cell biomarkers, and immune checkpoints. STRING database was used to analyze protein-protein interaction network information. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the function of P2RY8 and its interacting genes. For the purpose of validation, HCC tissue samples were collected from 64 patients who underwent radical surgery for HCC from June 2007 to November 2008, and the corresponding adjacent tissue samples were collected from 35 patients out of these patients (tissue chips were purchased from Shanghai Outdo Biotech Co., Ltd.); related clinical data and follow-up data were analyzed, and immunohistochemistry was used to measure the expression of P2RY8 in HCC and adjacent tissue samples. The t-test was used for comparison of normally distributed continuous data between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between two variables. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used to calculate survival rates. Results P2RY8 was overexpressed in HCC, and the expression level of P2RY8 could accurately differentiate tumor from normal tissue, with an area under the ROC curve of 0.794. The patients with a higher expression level of P2RY8 tended to have a better prognosis (P=0.005). The data from 64 clinical samples also confirmed that compared with the patients with a low expression level of P2RY8, the patients with a high expression level of P2RY8 had significantly higher 3-year survival rate (78.9% vs 46.2%, P=0.007), 5-year survival rate (76.3% vs 38.5%, P=0.002), and overall survival time [92.5 (48.8-102.0) months vs 33.0 (25.0-95.5) months, P=0.022], and the Kaplan-Meier survival curve further indicated that the expression level of P2RY8 was associated with the prognosis of HCC patients. In addition, P2RY8 was positively correlated with immune cell infiltration and immune checkpoint in HCC. The GO/KEGG pathway enrichment analyses showed that P2RY8 was enriched in the signal transduction pathways such as humoral immunity and cellular immunity. Conclusion P2RY8 participates in the development, progression, and immune regulation of HCC, and therefore, P2RY8 can serves as a potential biomarker and a therapeutic target for the diagnosis and prognosis of HCC. [ABSTRACT FROM AUTHOR]

Objective To identify the potential prognostic biomarkers of the immune-related genes signature for patients with hepatocellular carcinoma (HCC). Methods Original HCC data were downloaded from TCGA, and the immune activity of each sample was calculated by ssGSEA. HCC samples were divided into high and low immune cell infiltration groups by “GSVA” package and “hclust” package. The ESTIMATE algorithm scored the tumor microenvironment in each HCC sample. The “limma” package and Venn diagram identified effective immune-related genes. Univariate Cox, Lasso regression and multivariate Cox regression analyses were used to explore key genes. The “rms” package was used to create nomograms and draw calibration curves. Results Compared with the high immune cell infiltration group, the tumor purity of the samples in the low immune cell infiltration group was higher, the immune score, ESTIMATE score and stromal score were lower. In the high immune cell infiltration group, the immune components were more abundant, and the expression levels of TIGIT, PD-L1, PD-1, LAG3, TIM-3, CTLA4 and HLA family were higher. Multivariate Cox regression analysis showed that four immune-related genes (S100A9, HMOX1, IL18RAP and FCER1G) were used to construct the prognosis model. Compared with other clinical features, the risk score of this prognostic model was recognized as an independent prognostic factor. Conclusion This study identified the immune-related core genes which may be used in targeted therapy and immunotherapy of HCC. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression and prognostic value of FOXO1 gene in liver cancer tissues based on TCGA and HPA databases. Methods The RNA-seq data of FOXO1 gene in liver cancer were downloaded from TCGA. The difference of FOXO1 gene expression between tumor and adjacent tissues was obtained via R software. The correlation between FOXO1 and clinicopathological features of liver cancer patients was analyzed. Survival analysis was carried out to evaluate the prognostic significance of FOXO1 gene expression in liver cancer patients. Univariate and multivariate Cox analyses were performed to explore prognostic factors. The correlation between FOXO1 expression and TIICs in tumor microenvironment was performed by CIBERSORT. KEGG pathways enrichment analysis was performed for the potential function of FOXO1 gene in liver cancer. Results FOXO1 was downregulated in liver cancer tissues compared with normal tissues (P=1.321E-15). Survival analysis showed that high expression of FOXO1 was positively associated with favorable OS of liver cancer patients (P < 0.05). Clinical stage, T and M stages could be prognostic indicators while FOXO1 wasn't an independent prognostic factor in patients with liver cancer. In TME of liver cancer, the expression of FOXO1 was positively correlated with resting memory CD4 T cells and naive B cells while negatively related to activated memory CD4 T cells and macrophages M2. GSEA identified that FOXO1 participated in multiple cancer-related pathways. Conclusion FOXO1 is down-regulated in liver cancer tissues, and its expression level is associated with OS of patients. FOXO1 might be a biomarker related to the prognosis of liver cancer patients and is expected to be a target for diagnosis and treatment of liver cancer.

Objective To construct a prognostic model of laryngeal cancer based on pyroptosis-related lncRNAs. Methods Transcriptome expression and clinical data of patients with laryngeal cancer were downloaded from TCGA database. Differentially-expressed pyroptosis-related lncRNAs were selected using Wilcox rank sum test and Spearman correlation analysis. LncRNAs associated with patients’ prognosis were further selected using univariate Cox analysis (P<0.05), and a prognostic model was established using multivariate Cox regression. ROC curve was used to assess the sensitivity and specificity of this model. Results There were a total of 483 differentially-expressed pyroptosis-related lncRNAs in laryngeal cancer tissues, compared with normal laryngeal tissues (|logFC|≥1, FDR<0.05). Univariate Cox analysis showed that 23 differentially-expressed lncRNAs were associated with prognosis. Multivariate Cox regression analysis finally obtained a prognostic model based on 10 lncRNAs for predicting the survival of laryngeal carcinoma patients. AUC showed that the model had a good predictive ability (AUC>0.8). Conclusion Pyroptosisrelated lncRNAs can be used to predict the prognosis of patients with laryngeal cancer. [ABSTRACT FROM AUTHOR]

Objective To identify key biomarkers for predicting the response to immunotherapy and elucidate the possible underlying mechanism in lung adenocarcinoma based on whole-genome sequencing. Methods Data set of MSKCC (Science 2015) with lung adenocarcinoma from TCGA database were downloaded. According to the duration time of response to immunotherapy, two groups were divided: durable clinical benefit (DCB) group and non-durable clinical benefit (Non-DCB) group. The differences in gene mutation spectrum between the two groups were analyzed. The key genes and underlying biological functions of immunotherapy for lung adenocarcinoma were further analyzed. Results There were differences in gene mutation spectrum between the DCB group and the Non-DCB group. In the DCB group, these key genes were mainly involved in Ca signaling pathway, Rap1 and PI3K-AKT pathways. The top 6 hub genes (KRAS, PPP2CB, CDC20, DYNC1I2, BRCA1 and AKAP9) were screened using the PPI network analysis. CDC20 and BRCA1 were associated with the prognosis of lung adenocarcinoma patients. Conclusion The hub genes involved in the DCB group might be important to guide the classification of immune signature and improve precision immunotherapy for lung adenocarcinoma. In addition, CDC20 and BRCA1 might be potential therapeutic targets for immunotherapy of lung adenocarcinoma.

Objective To investigate the mRNA expression of SMAD9 in lung adenocarcinoma, and its relationship with clinicopathological parameters, survival and prognosis, so as to provide some valuable references for the screening and postoperative survival. Methods The expression of SMAD9 in tumor tissues (510 cases) and adjacent normal tissues (59 cases) of lung adenocarcinoma patients and its relationship with clinicopathological parameters and postoperative survival were analyzed based on the Cancer Genome Atlas (TCGA) database. The expression of SMAD9 in tumor tissues and adjacent normal tissues of lung adenocarcinoma patients, HBE malignant transformed cells induced by 3-MCA and lung adenocarcinoma cells were detected by quantitative real-time RT-PCR (qRT-PCR) and Western blotting. The effect of SMAD9 overexpression and interference on cell proliferation was detected by CCK-8 assay. Results The mRNA expression analysis of SMAD9 in TCGA database showed that the expression of SMAD9 was significantly lower in lung adenocarcinoma than adjacent normal tissues (P < 0.01). The results of qRT-PCR and Western blotting also showed that the expression of SMAD9 was significantly down-regulated in 3-MCA-induced HBE malignant transformed cells and lung adenocarcinoma tissues and cell lines (P < 0.05). The down-regulation of SMAD9 expression was closely correlated with N grade and tumor grade (P < 0.05). ROC curve analysis indicated that the mRNA expression of SMAD9 was a sensitive indicator of lung adenocarcinoma (AUC=0.903, 95%CI=0.868~0.938, P < 0.001). Kaplan-Meier analysis displayed that the survival time of patients with low expression of SMAD9 was significantly shorter than those with high expression (P < 0.05). Overexpression of SMAD9 inhibited the proliferation of lung adenocarcinoma cells (P < 0.01), and the proliferation of HBE cells was significantly enhanced after interfering with SMAD9 expression as compared with the control cells (P < 0.01). Conclusion SMAD9 gene expression is down-regulated in the incidence and development of lung adenocarcinoma. The expression of SMAD9 may be of great value for the screening and postoperative survival of lung adenocarcinoma patients.

Objective To construct a risk model for predicting the prognosis of papillary thyroid carcinoma (PTC) patients based on the expression of microRNAs (miRNA). Methods The original microRNAs sequencing data and corresponding clinical data of PTC patients were downloaded from the official website of TCGA database. The aberrant expression of microRNAs in PTC was screened by edgeR package in R 3.6.0 software. Univariate and multivariate Cox regression analyses as well as the Lasso regression analysis were utilized to screen out the microRNAs which were related to the prognosis of patients. Then, the risk score equation was established by multivariate Cox regression analysis and the risk prognosis model was constructed. The receiver operating characteristic (ROC) curve was utilized to evaluate the sensitivity and specificity of the model. Results Compared with normal tissues, 75 microRNAs (|log foldchange|≥2, FDR < 0.05) were dysregulated in PTC tissues. Multivariate Cox regression analysis revealed eight microRNAs (hsa-mir-6730, hsa-mir-4709, hsa-mir-196a-2, hsa-mir-146b, hsa-mir-6860, hsa-mir-509-3, hsa-mir-513c, hsa-mir-515-1) which could be used to construct risk model for predicting the prognosis of patients. The model had good sensitivity and specificity (AUC > 0.8). Conclusion A risk prediction model based on the expression of microRNAs has been successfully constructed, and the model could effectively predict the prognosis of thyroid cancer patients.

To explore the gene expression profile and screen disease-related biomarkers of thyroid cancer (THCA), the R/Bioconductor statistical platform was used for data processing and statistical analysis based on the THCA gene expression data in the TCGA database. Genes with fold change (FC) >2, P<0.05 between tumor and control tissues were selected as differentially expressed genes (DEGs) based on both edgeR package and limma package in R/Bioconductor. Then, the Medcalc statistical software was used for receiver operating characteristic (ROC) curve analysis to identify genetic biomarkers with potential application value as diagnostic markers. By combining the results from the two algorithms, a total of 1 945 DEGswere obtained in the THCA tumors (1 033 up-regulated genes and 912 down-regulated genes). Further, 11 DEGs were identified up-regulated in the tumor tissues, which showed good application values for distinguishing the tumor group from the control group. This study analyzed the THCA expression profile data in TCGA and identified DEGs that are significantly related to disease diagnosis, which can provide basis for exploring the mechanism and novel molecular markers of THCA. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship and significance of COL11A1 and MMP-11 genes with the progression and prognosis of bladder cancer.Methods The expressions profile and clinical information of COL11A1,MMP-11 genes in bladder cancer were downloaded from TCGA database,and the relationship between them was analyzed.Results The expression of COL11A1 in cancer tissue was higher than that in adjacent tissue,but the difference was not statistically significant(P >0.05);the expression of MMP-11 in cancer tissue was higher than that in adjacent tissue,the difference was statistically significant(P <0.05).The expressions of COL11A1 and MMP-11 were significantly correlated with age,T stage,N stage,pathological grade and clinical stage(P <0.05),and were not related to M stage and gender(P >0.05).The expressions of COL11A1 were not significantly associated with overall survival,3-year tumor-free survival,and 5-year tumorfree survival(P >0.05),but 3-year tumor-free survival rate,5-year tumor-free survival rate in the COL11A1 low expression group(34.2%,33.4%)were higher than those of the COL11A1 high expression group (28.7%,28.0%),the differences were statistically significant(P <0.05).The expression of MMP-11 was not significantly correlated with overall survival(P >0.05),but that were negatively correlated with 3-year tumorfree survival and 5-year tumor-free survival(P <0.05);the 3-year tumor-free survival rate and 5-year tumorfree survival rate in the MMP-11 low expression group(34.6%,33.9%)were higher than those of the MMP- 11 high expression group(28.3%,27.5%),the differences were statistically significant(P <0.05).The results of gene set enrichment analysis(GSEA)showed those COL11A1 high expression samples were enriched in cell adhesion molecules cams,ecm receptor interaction,focal adhesion,leukocyte transendothelial migration,natural killer cell mediated cytotoxicity,cytokine cytokine receptor interaction,chemokine signaling pathway and T cell receptor signaling pathway.The MMP-11 high expression samples were enriched gene sets such as ecm receptor interaction,focal adhesion,cell adhesion molecules cams,leukocyte transendothelial migration,cytokine cytokine receptor interaction,pathways in cance,chemokine signaling pathway,and lysosome.Conclusion COL11A1 and MMP-11 may be used as markers of bladder cancer progression,and their high expressions are a risk factor for bladder cancer progression and poor prognosis [ABSTRACT FROM AUTHOR]

Objective To evaluate the expression of semaphorin 5B (SEMA5B) in gastric adenocarcinoma and its relationship with prognosis. Methods In November 2019, the clinicopathological characteristics and SEMA5B mRNA expression data of 341 patients with gastric adenocarcinoma were collected through TCGA database. The relationship between SEMA5B expression in gastric adenocarcinoma tissues and clinical pathologic features and overall survival were analyzed. Gene Set Enrichment Analysis (GSEA) was used to analyze the signaling pathways regulated by SEMA5B. Results The expression level of SEMA5B mRNA in 341 gastric adenocarcinoma tissues was 0.577±0.587, in adjacent normal tissues was 0.132±0.075, the difference was statistically significant (P<0.001). The median survival time of 109 patients with high expression of SEMA5B mRNA was 14.5 months, 232 patients with low expression of SEMA5B mRNA was 17.9 months (P=0.047). Univariate analysis showed that the expression of SEMA5B mRNA was correlated with histological grade and T stage (P<0.05). The multivariate analysis revealed that age<65 years remained independently associated with overall survival, with a hazard ratio (HR) of 1.042 (95% CI: 1.021-1. 064). The multivariate analysis revealed that high expression of SEMA5b mRNA remained independently associated with overall survival, with a HR of 1.195 (95% CI: 0.925-2.551). GSEA showed that malignant tumor signaling pathways (P=0.008), MAPK signaling pathways (P=0.047) and Notch signaling pathways (P=0.029) were differentially enriched in SEMA5B highly expressed phenotype. Conclusions SEMA5B expression may be a potential prognostic molecular marker for prognosis of GAC patients. Moreover, malignant tumor signaling pathway, MAPK signaling pathway and Notch signaling pathway may be the key pathway regulated by SEMA5B in GAC. [ABSTRACT FROM AUTHOR]

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

【目的】利用生物信息学的方法，对GEO和TCGA两个基因组学数据库进行分析，探究与前列腺癌相关的差异基因及相关的调控网络。【方法】综合GEO数据库的前列腺癌基因表达芯片数据（GSE46602、GSE55945）和TCGA数据库的RNA-seq数据，利用GEO2R及R语言的edgeR包进行基因差异分析，获得共同的显著差异基因，结合R语言的clusterProfiler包进行GO功能分析及KEGG通路分析，同时利用string网站进行蛋白互作网络分析，筛选出前列腺癌中调节蛋白表达量的关键基因，再结合TCGA临床随访数据分析关键节点基因的临床预后价值。【结果】获得共同差异基因共278个，其中表达上调100个，表达下调178个，它们与上皮细胞的调节增殖、含苯化合物的代谢过程等功能以及谷胱甘肽代谢和粘着斑等信号通路密切相关。蛋白互作网络分析结果得出3个重点蛋白表达模块以及12个关键节点基因。在这些关键基因中，EDN3、EDNRB和AMACR与前列腺癌患者的生存率密切相关。【结论】通过对前列腺癌基因芯片和RNA-seq数据的生物信息学分析，我们发现EDN3、EDNRB与AMACR很可能在前列腺癌的发生发展过程中发挥重要作用。

Copyright of Journal of South China University of Technology (Natural Science Edition) is the property of South China University of Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

【目的】采用生物信息学方法探究肝细胞癌（HCC）发生的关键基因，望有助于了解HCC发生发展的分子机制。【方法】从GEO数据库中选择基因表达谱GSE76427，该数据集包含115例肝癌组织样本和52例肝癌临近非肿瘤组织样本。通过GEO2R工具在线分析，筛选出肝癌组织中差异表达基因（DEG），利用GO数据库获取DEG的功能注释，利用KEGG数据库进行通路富集分析。基于STRING数据库，利用MCC算法，筛选具有高度连接性的关键基因,基于TCGA数据库在线软件分析关键基因的预后效应。【结果】共筛选出190个DEG，其中，上调基因有16个，下调基因有174个。功能富集分析显示，下调的差异基因显著富集于细胞对铬离子、锌离子的反应，也可能参与环氧化酶P450途径和氧化还原反应等功能。下调的差异基因可能参与视黄醇的新陈代谢和矿物质的吸收等通路功能。筛选出15 个具有高度连接性的关键基因，发现CDC20、KIAA0101、PRC1、PTTG1 和UBE2C 等5个基因与乙肝相关性肝癌的患者总体生存率（OS）相关。PTTG1 的诊断效能最佳。【结论】CDC20、KIAA0101、PRC1、PTTG1 和UBE2C 可能在乙型肝炎病毒相关性肝癌的发生发展中发挥重要作用。

Objective: To investigate the expression and significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods: PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas (TCGA) database and tissue genotypic expression database (GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results: The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue (3.05±0.72 vs. 0.33±0.16, P =0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect ( P <0.05). Survival analysis showed that the progression free survival time ( P =0.033) and overall survival time ( P =0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival ( P <0.05). The progression-free survival ( P =0.016) and overall survival ( P =0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival ( P <0.05). Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis (GSEA) showed that the Wnt/β-catenin signaling pathway ( P =0.023), the MAPK signaling pathway ( P =0.029) and glycolysis related pathway ( P =0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions: PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/β-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis.

Objective: To identify tumor microenvironment (TME)- related genes associated with the occurrence of invasive breast cancer as potential prognostic biomarkers and therapeutic targets., Methods: RNA transcriptome data and clinically relevant data were retrieved from TCGA database, and the StromalScore and ImmuneScore were calculated using the ESTIMATE algorithm. The differentially expressed genes (DEGs) were screened by taking the intersection. A protein- protein interaction network was established, and univariate COX regression analysis was used to identify the core genes among the DEGs. A core gene was selected for GSEA and CIBERSORT analysis to determine the function of the core gene and the proportion of tumor-infiltrating immune cells, respectively. Western blotting and qRT-PCR were performed to verify the expression level of CD40LG in breast cancer cell lines and clinical specimens., Results: A total of 1222 samples (124 normal and 1098 tumor samples) were extracted from TCGA for analysis, from which 487 DEGs were identified. These genes were mainly enriched in immune-related pathways, and crossover analysis identified 11 key genes (CD40LG, ITK, CD5, CD3E, SPN, IL7R, CD48, CCL19, CD2, CD52, and CD2711) associated with breast cancer TME status. CD40LG was selected as the core gene, whose high expression was found to be associated with a longer overall survival of breast cancer patients ( P =0.002), and its expression level differed significantly with TNM stage and tumor size ( P < 0.05). GSEA and CIBERSORT analyses indicated that CD40LG expression level was associated with immune activity in the TME. Western blotting and qRT-PCR showed that the protein and mRNA expression of CD40LG were significantly lower in breast cancer cells and cancer tissues than in normal breast cells and adjacent tissues., Conclusions: The high expression of CD40LG in TME is positively correlated with the survival of patients with invasive breast cancer, suggesting its value as a potential new biomarker for predicting prognosis of the patients.

Objective: To identify the key hub genes in prostate cancer metastasis based on weighted gene co-expression network analysis (WGCNA) and verify the identified genes., Methods: Whole-genome chip data GSE6919 of prostate cancer study were analyzed using principal component analysis (PCA), and the differentially expressed genes (DEGs) were analyzed using R software. WGCNA was performed to construct a gene co-expression network for screening the key genes. TCGA database was used to explore the expressions of the DEGs and their association with the prognosis. To validate the results, we designed siRNA fragments targeting the metastasis-related gene HNRNPA2B1 , and observed its effect on growth, apoptosis, clone formation, migration and invasion of prostate cancer cell lines using MTT assay, flow cytometry, clone formation assay, and Transwell assay., Results: PCA analysis showed obvious clustering of significant DEGs in metastatic cancer group. The modules obtained by WGCNA analysis in metastasis group involved stem cell differentiation, amino acid metabolism and immune response. Further screening of the genes identified 3 genes related with prostate cancer occurrence ( BDH1 , PAK4 and EXTL3 ) and another 3 with prostate cancer metastasis ( NKTR , CTBP2 and HNRNPA2B1 ), which were shown to have differential expressions in TCGA database and were correlated with the patient's overall survival. In the cell experiment, PC3 and LNCap cells transfected with the siRNA fragment targeting HNRNPA2B1 showed obvious growth inhibition with increased cell apoptosis, lowered clone formation ability, and suppressed capacities for migration and invasion., Conclusion: We identified 3 hub genes related with the occurrence ( BDH1 , PAK4 and EXTL3 ) and another 3 with metastasis of prostate cancer ( NKTR , CTBP2 and HNRNPA2B1 ) using WGCNA, which provides a new approach for studying the regulatory mechanisms of prostate cancer.

Objective: To evaluate the expression of semaphorin 5B (SEMA5B) in gastric adenocarcinoma and its relationship with prognosis. Methods: In November 2019, the clinicopathological characteristics and SEMA5B mRNA expression data of 341 patients with gastric adenocarcinoma were collected through TCGA database. The relationship between SEMA5B expression in gastric adenocarcinoma tissues and clinical pathologic features and overall survival were analyzed. Gene Set Enrichment Analysis (GSEA) was used to analyze the signaling pathways regulated by SEMA5B. Results: The expression level of SEMA5B mRNA in 341 gastric adenocarcinoma tissues was 0.577±0.587, in adjacent normal tissues was 0.132±0.075, the difference was statistically significant ( P <0.001). The median survival time of 109 patients with high expression of SEMA5B mRNA was 14.5 months, 232 patients with low expression of SEMA5B mRNA was 17.9 months ( P =0.047). Univariate analysis showed that the expression of SEMA5B mRNA was correlated with histological grade and T stage ( P <0.05). The multivariate analysis revealed that age<65 years remained independently associated with overall survival, with a hazard ratio( HR ) of 1.042 (95% CI: 1.021-1.064). The multivariate analysis revealed that high expression of SEMA5b mRNA remained independently associated with overall survival, with a HR of 1.195 (95% CI: 0.925-2.551). GSEA showed that malignant tumor signaling pathways ( P =0.008), MAPK signaling pathways ( P =0.047) and Notch signaling pathways ( P =0.029) were differentially enriched in SEMA5B highly expressed phenotype. Conclusions: SEMA5B expression may be a potential prognostic molecular marker for prognosis of GAC patients. Moreover, malignant tumor signaling pathway, MAPK signaling pathway and Notch signaling pathway may be the key pathway regulated by SEMA5B in GAC.

Objective: To analyze the gene mutation profile in malignant pleural mesothelioma (MPM) and investigate the expression of high-frequency mutant genes and its relationship with clinicopathological parameters. To screen out key genes and clinicopathologic factors related to the prognosis of MPM patients. Methods: The second generation sequencing data, somatic mutation data and clinical pathological data of 86 MPM cases and gene chip expression data of 89 MPM cases were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) in March 2020. Summarize the gene mutation profile of tissue samples in the TCGA database and analyze the relationship between the expression level of high-frequency mutation genes and the clinicopathological characteristics, asbestos exposure history and prognosis of MPM patients. The genes significantly related to MPM prognosis were screened out for gene set enrichment analysis (GSEA) . Survival analysis and GSEA were performed for the selected key genes and clinicopathological features verification using the microarray expression data from the GEO database. Results: The top 10 genes with highest single nucleotide variations frequencies were BAP1, NF2, TP53, TTN, SETD2, LATS2, CCDC168, FAT4, PTCH1 and ZNF469. The high expression rates of NF2, TP53, SETD2 and CCDC168 genes in wild type were higher than those of mutated type, and the differences were statistically significant ( P <0.05) . Cox multivariate analysis of TCGA data showed that MPM patients with epithelial type ( HR =0.425, 95% CI : 0.235-0.767, P <0.01) and SETD2 low expression ( HR =0.516, 95% CI : 0.307-0.868, P =0.011) had lower risk of death. The survival analysis of GEO data verified that patients with epithelial type MPM had longer survival time, while patients with sarcoma type MPM had shortest survival time ( P <0.01) . GSEA showed that SETD2 was involved in G2M checkpoint, E2F targets, MYC signaling pathways, protein secretion, mitotic spindle, MTORC1 pathway, TGF-β pathway, androgen response and uv response. Conclusion: MPM is accompanied with higher frequency of gene mutations represented by BAP1, NF2, TP53, TTN, SETD2, LATS2 and so on. SETD2 expression level and epithelia type of MPM may be influential factors for MPM prognosis.

Objective: To evaluate the expression and prognostic value of superoxide dismutase 2 (SOD2) in breast cancer and explore its possible role in the occurrence and progression of breast cancer., Methods: We performed bioinformatics analysis of the TCGA data for the expression and clinical relevance of SOD2 in patients with breast cancer. Gene enrichment analysis (GSEA) was performed using the KEGG gene set, the protein interaction network was constructed using the STRING database, and the key genes were screened using Cytoscape software. We also collected 60 pairs of primary breast cancer tissue samples and adjacent samples for detecting SOD2 expressions using immunohistochemistry and RT-qPCR and analyzed the correlation of SOD2 expression with the clinicopathological parameters of the patients., Results: The expression of SOD2 was significantly lower in breast cancer tissue than in adjacent tissues with significant correlation with TNM stage and axillary lymph node metastasis ( P &lt; 0.05). Kaplan-Meier survival analysis showed that the recurrence-free survival, distant metastasis-free survival (RFS) and post-progressive survival were significantly shorted in patients with high SOD2 expression than in those with low SOD2 expression ( P &lt; 0.05). GSEA enrichment analysis indicated that SOD2 played an important role in the JAK-STAT signaling pathway. IL10 and STAT4 were identified as the key genes in the PPI network, and they were both positively correlated with SOD2. In the 60 pairs of clinical samples, SOD2 was highly expressed in breast cancer tissues with close correlation with axillary lymph node metastasis and the expressions of estrogen receptor and androgen receptor ( P &lt; 0.05)., Conclusions: The expression of SOD2 in breast cancer is significantly correlated with TNM stage and axillary lymph node metastasis. SOD2 may affect the proliferation, invasion and metastasis of breast cancer cells possibly by regulating IL10 and/or STAT4 to affect the JAK/STAT signaling pathway.

Objective: To investigate the prognosis-related miRNA histological features and clinical significance of lung adenocarcinoma., Methods: Using The Cancer Genome Atlas (TCGA) data, the miRNA expression profile data of human lung adenocarcinoma were searched for differential analysis, and the prognosis-related miRNAs were screened by Cox risk regression model. The targeted miRNAs were predicted by mirwalk analysis platform, KEGG functional enrichment analysis, and finally, predict the function of prognosis-related miRNAs., Results: A total of 46 differential miRNAs in lung adenocarcinoma were screened, including 19 up-regulated and 27 down-regulated. Six prognostic-related miRNAs were screened by Cox survival analysis, namely hsa-mir-21, hsa-mir-142, hsa-mir-200a high expression, hsa-mir-101, hsa-let-7c, hsa-mir-378e low expression, hsa-mir-21 and hsa-mir-378e were associated with poor prognosis in patients with lung adenocarcinoma, and the survival time was shortened significantly ( P <0.05, AUC=0.618). KEGG analysis showed that the above prognosis-related miRNA targeting regulatory genes were related with immune response pathways, miRNA and cancer pathways, metabolic pathways and so on., Conclusions: Hsa-mir-21 and hsa-mir-378e are associated with poor prognosis of lung adenocarcinoma, and may be used as a molecular marker for prognosis of lung adenocarcinoma after further clinical verification.