scholarly journals Screening of gene markers related to the prognosis of metastatic skin cutaneous melanoma based on Logit regression and survival analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guoliang Jia ◽  
Zheyu Song ◽  
Zhonghang Xu ◽  
Youmao Tao ◽  
Yuanyu Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cutaneous Melanoma ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Training Dataset ◽  
Validation Dataset ◽  
Survival Prognosis ◽  
Gene Markers ◽  
Clinical Prognosis ◽  
Logit Regression

Abstract Background Bioinformatics was used to analyze the skin cutaneous melanoma (SKCM) gene expression profile to provide a theoretical basis for further studying the mechanism underlying metastatic SKCM and the clinical prognosis. Methods We downloaded the gene expression profiles of 358 metastatic and 102 primary (nonmetastatic) CM samples from The Cancer Genome Atlas (TCGA) database as a training dataset and the GSE65904 dataset from the National Center for Biotechnology Information database as a validation dataset. Differentially expressed genes (DEGs) were screened using the limma package of R3.4.1, and prognosis-related feature DEGs were screened using Logit regression (LR) and survival analyses. We also used the STRING online database, Cytoscape software, and Database for Annotation, Visualization and Integrated Discovery software for protein–protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses based on the screened DEGs. Results Of the 876 DEGs selected, 11 (ZNF750, NLRP6, TGM3, KRTDAP, CAMSAP3, KRT6C, CALML5, SPRR2E, CD3G, RTP5, and FAM83C) were screened using LR analysis. The survival prognosis of nonmetastatic group was better compared to the metastatic group between the TCGA training and validation datasets. The 11 DEGs were involved in 9 KEGG signaling pathways, and of these 11 DEGs, CALML5 was a feature DEG involved in the melanogenesis pathway, 12 targets of which were collected. Conclusion The feature DEGs screened, such as CALML5, are related to the prognosis of metastatic CM according to LR. Our results provide new ideas for exploring the molecular mechanism underlying CM metastasis and finding new diagnostic prognostic markers.

scholarly journals Identification of Immune Infiltration-related Gene Signature Associated with Prognosis and Immune Features in Stomach Adenocarcinoma

2021 ◽  
Author(s):  
Ya Yang ◽  
Xintan Zhang ◽  
Tingxuan Li ◽  
Yue Zhang ◽  
Xiaoxiao Zuo
Keyword(s):  
Gene Expression ◽  
Clinical Data ◽  
Expression Profiles ◽  
Prognostic Score ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Validation Dataset ◽  
Prognostic Signature ◽  
Survival Prognosis ◽  
Stomach Adenocarcinoma

Abstract Background: Immune infiltrated genes (IIGs) have been identified to associated with the prognosis of various cancers, but their expression and prognostic significance remain largely unclear in stomach adenocarcinoma (STAD).Methods: Gene expression profiles and clinical data of STAD patients were downloaded from The Cancer Genome Atlas (TCGA) as a training dataset (n = 375) and Gene Expression Omnibus (GEO) databases as a validation dataset (n = 300). Construction of high and low immune cell infiltration groups was performed by single sample gene set enrichment analysis (ssGSEA) and evaluated by ESTIMATE algorithm-derived immune scores. The overlapping differentially expressed genes (DEGs) in tumor vs. normal and Immunity-H vs. Immunity-L were selected as differentially expressed immune infiltrated genes (DEIIGs), which were used to construct DEIIG prognostic signature and its performance was validated using validation dataset. Moreover, the association between clinical data and immune features were explored. Furthermore, ADH4 and ANGPT2 were selected for analyzing their expression and prognostic values in STAD patients.Results: A total of 191 overlapping DEGs, including 6 lnRNAs and 185 mRNA were identified. Consecutively, 9 DEIIG prognostic signature (LINC00843, ADH4, ANGPT2, APOA1, ASLC2, GFRA1, KIAA1549L, MTTP and PROC) were identified as risk signature and Kaplan-Meier curve and ROC curve verified its performance in TCGA and GEO datasets. Total five clinical outcomes (age, pathologic T, radiotherapy, tumor recurrence and prognostic score model status) were identified to be associated with the survival prognosis of STAD patients. The TIMER algorithm revealed that B cell, T cell CD4+, neutrophil, macrophage and myeloid dendritic cell were positively correlated with STAD prognosis, while CD8+ was negatively correlated with STAD prognosis. Additionally, we validated that higher ADH4 and lower ANGPT2 predicted better survival prognosis in STAD patients.Conclusion: We constructed and verified a robust signature of nine DEIIG prognostic signature for the prediction of STAD patient survival.

scholarly journals 90-Gene Expression Profiling for Tissue Origin Diagnosis of Cancer of Unknown Primary

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Zhang ◽  
Lei Xia ◽  
Dawei Ma ◽  
Jing Wu ◽  
Xinyu Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Cancer Of Unknown Primary ◽  
The Cancer Genome Atlas ◽  
Unknown Primary ◽  
Gene Expression Assay ◽  
Primary Location ◽  
Cancer Genome Atlas ◽  
Expression Characteristics

Cancer of unknown primary (CUP), in which metastatic diseases exist without an identifiable primary location, accounts for about 3–5% of all cancer diagnoses. Successful diagnosis and treatment of such patients are difficult. This study aimed to assess the expression characteristics of 90 genes as a method of identifying the primary site from CUP samples. We validated a 90-gene expression assay and explored its potential diagnostic utility in 44 patients at Jiangsu Cancer Hospital. For each specimen, the expression of 90 tumor-specific genes in malignant tumors was analyzed, and similarity scores were obtained. The types of malignant tumors predicted were compared with the reference diagnosis to calculate the accuracy. In addition, we verified the consistency of the expression profiles of the 90 genes in CUP secondary malignancies and metastatic malignancies in The Cancer Genome Atlas. We also reported a detailed description of the next-generation coding sequences for CUP patients. For each clinical medical specimen collected, the type of malignant tumor predicted and analyzed by the 90-gene expression assay was compared with its reference diagnosis, and the overall accuracy was 95.4%. In addition, the 90-gene expression profile generally accurately classified CUP into the cluster of its primary tumor. Sequencing of the exome transcriptome containing 556 high-frequency gene mutation oncogenes was not significantly related to the 90 genes analysis. Our results demonstrate that the expression characteristics of these 90 genes can be used as a powerful tool to accurately identify the primary sites of CUP. In the future, the inclusion of the 90-gene expression assay in pathological diagnosis will help oncologists use precise treatments, thereby improving the care and outcomes of CUP patients.

scholarly journals Integrating Genetic and Transcriptomic Data to Reveal Pathogenesis and Prognostic Markers of Pancreatic Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaisong Bai ◽  
Tong Zhao ◽  
Yilong Li ◽  
Xinjian Li ◽  
Zhantian Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Adenocarcinoma ◽  
Somatic Mutation ◽  
Somatic Mutations ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genomic Variation ◽  
The Cancer Genome Atlas ◽  
Driver Genes

Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies and mortality for PAAD have remained increasing under the conditions of substantial improvements in mortality for other major cancers. Although multiple of studies exists on PAAD, few studies have dissected the oncogenic mechanisms of PAAD based on genomic variation. In this study, we integrated somatic mutation data and gene expression profiles obtained by high-throughput sequencing to characterize the pathogenesis of PAAD. The mutation profile containing 182 samples with 25,470 somatic mutations was obtained from The Cancer Genome Atlas (TCGA). The mutation landscape was generated and somatic mutations in PAAD were found to have preference for mutation location. The combination of mutation matrix and gene expression profiles identified 31 driver genes that were closely associated with tumor cell invasion and apoptosis. Co-expression networks were constructed based on 461 genes significantly associated with driver genes and the hub gene FAM133A in the network was identified to be associated with tumor metastasis. Further, the cascade relationship of somatic mutation-Long non-coding RNA (lncRNA)-microRNA (miRNA) was constructed to reveal a new mechanism for the involvement of mutations in post-transcriptional regulation. We have also identified prognostic markers that are significantly associated with overall survival (OS) of PAAD patients and constructed a risk score model to identify patients’ survival risk. In summary, our study revealed the pathogenic mechanisms and prognostic markers of PAAD providing theoretical support for the development of precision medicine.

scholarly journals Exploration and validation of a novel prognostic signature based on comprehensive bioinformatics analysis in hepatocellular carcinoma

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Xiaofei Wang ◽  
Jie Qiao ◽  
Rongqi Wang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Risk Score ◽  
Expression Profiles ◽  
Univariate Analysis ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Good Prediction ◽  
Expression Levels

Abstract The present study aimed to construct a novel signature for indicating the prognostic outcomes of hepatocellular carcinoma (HCC). Gene expression profiles were downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. The prognosis-related genes with differential expression were identified with weighted gene co-expression network analysis (WGCNA), univariate analysis, the least absolute shrinkage and selection operator (LASSO). With the stepwise regression analysis, a risk score was constructed based on the expression levels of five genes: Risk score = (−0.7736* CCNB2) + (1.0083* DYNC1LI1) + (−0.6755* KIF11) + (0.9588* SPC25) + (1.5237* KIF18A), which can be applied as a signature for predicting the prognosis of HCC patients. The prediction capacity of the risk score for overall survival was validated with both TCGA and ICGC cohorts. The 1-, 3- and 5-year ROC curves were plotted, in which the AUC was 0.842, 0.726 and 0.699 in TCGA cohort and 0.734, 0.691 and 0.700 in ICGC cohort, respectively. Moreover, the expression levels of the five genes were determined in clinical tumor and normal specimens with immunohistochemistry. The novel signature has exhibited good prediction efficacy for the overall survival of HCC patients.

scholarly journals Integrative transcriptome data mining for identification of core lncRNAs in breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7821 ◽  
Author(s):  
Xiaoming Zhang ◽  
Jing Zhuang ◽  
Lijuan Liu ◽  
Zhengguo He ◽  
Cun Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Prognostic Value ◽  
Early Stage ◽  
Expression Profiles ◽  
Diagnostic Value ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Data Set

Background Cumulative evidence suggests that long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. This study aims to identify lncRNAs that can serve as new biomarkers for breast cancer diagnosis or screening. Methods First, the linear fitting method was used to identify differentially expressed genes from the breast cancer RNA expression profiles in The Cancer Genome Atlas (TCGA). Next, the diagnostic value of all differentially expressed lncRNAs was evaluated using a receiver operating characteristic (ROC) curve. Then, the top ten lncRNAs with the highest diagnostic value were selected as core genes for clinical characteristics and prognosis analysis. Furthermore, core lncRNA-mRNA co-expression networks based on weighted gene co-expression network analysis (WGCNA) were constructed, and functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The differential expression level and diagnostic value of core lncRNAs were further evaluated by using independent data set from Gene Expression Omnibus (GEO). Finally, the expression status and prognostic value of core lncRNAs in various tumors were analyzed based on Gene Expression Profiling Interactive Analysis (GEPIA). Results Seven core lncRNAs (LINC00478, PGM5-AS1, AL035610.1, MIR143HG, RP11-175K6.1, AC005550.4, and MIR497HG) have good single-factor diagnostic value for breast cancer. AC093850.2 has a prognostic value for breast cancer. AC005550.4 and MIR497HG can better distinguish breast cancer patients in early-stage from the advanced-stage. Low expression of MAGI2-AS3, LINC00478, AL035610.1, MIR143HG, and MIR145 may be associated with lymph node metastasis in breast cancer. Conclusion Our study provides candidate biomarkers for the diagnosis and prognosis of breast cancer, as well as a bioinformatics basis for the further elucidation of the molecular pathological mechanism of breast cancer.

scholarly journals Identification and Validation of a Predictive Immune-related Genes Signature for the Prognosis of Cholangiocarcinoma

2020 ◽  
Author(s):  
Rui Zhang ◽  
Chen Chen ◽  
Qi Li ◽  
Jialu Fu ◽  
Dong Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
High Risk ◽  
Risk Score ◽  
Risk Model ◽  
Predictive Accuracy ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Immune Related Genes

Abstract Background: Immune-related genes (IRGs) play a crucial role in the initiation and progression of cholangiocarcinoma (CCA). However, immune signatures have rarely been used to predict prognosis of CCA. The aim of this study was to construct a novel model for CCA to predict survival based on IRGs expression data.Methods: The gene expression profiles and clinical data of CCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were integrated to establish and validate prognostic IRG signatures. Differentially expressed immune-related genes were screened. Univariate and multivariate Cox analysis were performed to identify prognostic IRGs, and the risk model that predicts outcomes was constructed. Furthermore, receiver operating characteristic (ROC) and Kaplan-Meier curve were plotted to examine predictive accuracy of the model, and a nomogram was constructed based on IRGs signature, combining with other clinical characteristics. Finally, CIBERSORT was used to analyze the association of immune cells infiltration with risk score.Results: We identified that 223 IRGs were significantly dysregulated in patients with CCA, among which five IRGs (AVPR1B, CST4, TDGF1, RAET1E and IL9R) were identified as robust indicators for overall survival (OS), and a prognostic model was built based on the IRGs signature. Meanwhile, patients with high risk had worse OS in training and validation cohort, and the area under the ROC was 0.898 and 0.846, respectively. Nomogram demonstrated that immune risk score contributed much more points than other clinicopathological variables, with a C-index of 0.819 (95% CI, 0.727-0.911). Finally, we found that IRGs signature was positively correlated with the proportion of CD8+ T cells, neurophils and T gamma delta, while negatively with that of CD4+ memory resting T cells.Conclusions: We established and validated an effective five IRGs-based prediction model for CCA, which could accurately classify patients into groups with low and high risk of poor prognosis.

scholarly journals Identification of an extracellular vesicle-related gene signature in the prediction of pancreatic cancer clinical prognosis

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Dafeng Xu ◽  
Yu Wang ◽  
Kailun Zhou ◽  
Jincai Wu ◽  
Zhensheng Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Immune Cells ◽  
Prognostic Value ◽  
Tumor Tissue ◽  
Clinical Stage ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Clinical Prognosis

Abstract Although extracellular vesicles (EVs) in body fluid have been considered to be ideal biomarkers for cancer diagnosis and prognosis, it is still difficult to distinguish EVs derived from tumor tissue and normal tissue. Therefore, the prognostic value of tumor-specific EVs was evaluated through related molecules in pancreatic tumor tissue. NA sequencing data of pancreatic adenocarcinoma (PAAD) were acquired from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). EV-related genes in pancreatic cancer were obtained from exoRBase. Protein–protein interaction (PPI) network analysis was used to identify modules related to clinical stage. CIBERSORT was used to assess the abundance of immune and non-immune cells in the tumor microenvironment. A total of 12 PPI modules were identified, and the 3-PPI-MOD was identified based on the randomForest package. The genes of this model are involved in DNA damage and repair and cell membrane-related pathways. The independent external verification cohorts showed that the 3-PPI-MOD can significantly classify patient prognosis. Moreover, compared with the model constructed by pure gene expression, the 3-PPI-MOD showed better prognostic value. The expression of genes in the 3-PPI-MOD had a significant positive correlation with immune cells. Genes related to the hypoxia pathway were significantly enriched in the high-risk tumors predicted by the 3-PPI-MOD. External databases were used to verify the gene expression in the 3-PPI-MOD. The 3-PPI-MOD had satisfactory predictive performance and could be used as a prognostic predictive biomarker for pancreatic cancer.

scholarly journals Predictive value of m5C regulatory gene expression in pancreatic adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiao Yu ◽  
Qiyao Zhang ◽  
Fang Gao ◽  
Menggang Zhang ◽  
Qingyuan Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Adenocarcinoma ◽  
Regulatory Gene ◽  
Copy Number Variations ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Validation Dataset ◽  
Genes Encoding ◽  
Patient Prognosis ◽  
Regulated Gene Expression

AbstractPancreatic adenocarcinoma (PAAD) is the most malignant digestive tumor. The global incidence of pancreatic cancer has been rapidly trending upwards, necessitating an exploration of potential prognostic biomarkers and mechanisms of disease development. One of the most prevalent RNA modifications is 5-methylcytosine (m5C); however, its contribution to PAAD remains unclear. Data from The Cancer Genome Atlas (TCGA) database, including genes, copy number variations (CNVs), and simple nucleotide variations (SNVs), were obtained in the present study to identify gene signatures and prognostic values for m5C regulators in PAAD. Regulatory gene m5C changes were significantly correlated with TP53, BRCA1, CDKN2A, and ATM genes, which play important roles in PAAD pathogenesis. In particular, there was a significant relationship between m5C regulatory gene CNVs, especially in genes encoding epigenetic “writers”. According to m5C-regulated gene expression in clinically graded cases, one m5C-regulated genes, DNMT3A, showed both a strong effect on CNVs and a significant correlation between expression level and clinical grade (P < 0.05). Furthermore, low DNMT3A expression was not only associated with poor PAAD patient prognosis but also with the ribosomal processing. The relationship between low DNMT3A expression and poor prognosis was confirmed in an International Cancer Genome Consortium (ICGC) validation dataset.

scholarly journals In Silico Discovery of Candidate Drugs against Covid-19

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 404 ◽  
Author(s):  
Claudia Cava ◽  
Gloria Bertoli ◽  
Isabella Castiglioni
Keyword(s):  
Gene Expression ◽  
In Silico ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Basic Mechanism ◽  
Cell Receptor ◽  
The Cancer Genome Atlas ◽  
Pathway Enrichment Analysis

Previous studies reported that Angiotensin converting enzyme 2 (ACE2) is the main cell receptor of SARS-CoV and SARS-CoV-2. It plays a key role in the access of the virus into the cell to produce the final infection. In the present study we investigated in silico the basic mechanism of ACE2 in the lung and provided evidences for new potentially effective drugs for Covid-19. Specifically, we used the gene expression profiles from public datasets including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, Gene Ontology and pathway enrichment analysis to investigate the main functions of ACE2-correlated genes. We constructed a protein-protein interaction network containing the genes co-expressed with ACE2. Finally, we focused on the genes in the network that are already associated with known drugs and evaluated their role for a potential treatment of Covid-19. Our results demonstrate that the genes correlated with ACE2 are mainly enriched in the sterol biosynthetic process, Aryldialkylphosphatase activity, adenosylhomocysteinase activity, trialkylsulfonium hydrolase activity, acetate-CoA and CoA ligase activity. We identified a network of 193 genes, 222 interactions and 36 potential drugs that could have a crucial role. Among possible interesting drugs for Covid-19 treatment, we found Nimesulide, Fluticasone Propionate, Thiabendazole, Photofrin, Didanosine and Flutamide.

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