scholarly journals Overexpressing PTTG family genes predict poor prognosis in kidney renal clear cell carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yonghui Gui ◽  
Xueni Liu ◽  
Chao Wang ◽  
Peng Yang
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Renal Clear Cell Carcinoma ◽  
Expression Level ◽  
Pathway Enrichment Analysis ◽  
Term Survival ◽  
Clinical Indicators

Abstract Background Pituitary tumor transforming genes (PTTG1, PTTG2, and PTTG3P) play key roles in the pathogenesis and development of human cancers. The studies show that overexpression of the PTTG genes is associated with tumor progression and migration. However, the function of the PTTG genes in the prognostic value of kidney renal clear cell carcinoma is rarely known by people. Methods The expression of PTTG family genes was analyzed by the ONCOMINE, Human Protein Atlas, GEPIA2, and UALCAN database. The relationship between PTTG family genes expression level and clinical indicators including prognostic data in kidney renal clear cell carcinoma was analyzed by GEPIA2, TCGA portal, and UALCAN. cBioPortal database was used to analyze the genetic mutations of differentially expressed PTTG family members. Similar genes of the PTTG family (90 in total) obtained from GEPIA2 and Metascape were used for GO enrichment to explore the interaction among similar genes. The online tools of Metascape and STRING were used for functional and pathway enrichment analysis. Results PTTG1, 2, and 3P mRNA and protein expression upregulated in kidney renal clear cell carcinoma kidney renal clear cell carcinoma patients compared with normal tissues. And higher expression level of PTTG family genes was associated with shorter overall survival (OS) and disease-free survival (DFS). Furthermore, overexpression of the PTTG family genes had been found correlated with individual cancer stages and pathological tumor grades. In addition, 18% of mutations in the PTTG family genes were associated with short-term survival in kidney renal clear cell carcinoma patients. Conclusions A single PTTG gene or PTTG family genes as a whole may be a potential prognostic biomarker for kidney renal clear cell carcinoma.

scholarly journals Prognostic Impact of MITD1 and Associates With Immune Infiltration in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110362
Author(s):  
Chujie Chen ◽  
Yiyu Sheng
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Functional Enrichment ◽  
Prognostic Impact ◽  
Clinical Value ◽  
Immune Infiltration ◽  
Potential Biomarker

Kidney renal clear cell carcinoma (KIRC) is one of the most malignant diseases with poor survival rate over the world. The tumor microenvironment (TME) is highly related to the oncogenesis, development, and prognosis of KIRC. Thus, making the identification of KIRC biomarkers and immune infiltrates critically important. Microtubule Interacting and Trafficking Domain containing 1(MITD1) was reported to participate in cytokinesis of cell division. In the present study, multiple bioinformatics tools and databases were applied to investigate the expression level and clinical value of MITD1 in KIRC. We found that the expression of MITD1 was significantly increased in KIRC tissues. Further, the KIRC patients with high MITD1 levels showed a worse overall survival (OS) rate and disease free survival (DFS) rate. Otherwise, we found a significant correlation MITD1 expression and the abundance of CD8+ T cells. Functional enrichment analyses revealed that immune response and cytokine-cytokine receptor are very critical signaling pathways which associated with MITD1 in KIRC. In conclusion, our findings indicated that MITD1 may be a potential biomarker and associated with immune infiltration in KIRC.

scholarly journals Identification of Tumor Microenvironment-Related Genes in Kidney Renal Clear Cell Carcinoma Patients via Bioinformatic Analysis

2021 ◽  
Author(s):  
Rongjiong Zheng ◽  
Yaosen SHao ◽  
Mingming Wang ◽  
Yeli Tang ◽  
Meiling Hu
Keyword(s):  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment

Abstract BackgroundTumor microenvironment has been implicated in the development and progression of cancers. However, the prognostic significance of tumor microenvironment-related genes in kidney renal clear cell carcinoma (KIRC) remains unclear. MethodsIn this study, we obtained and analyzed gene expression profiles from The Cancer Genome Atlas database. Stromal and immune scores were calculated based on the ESTIMATE algorithm. ResultsIn the discovery series of 537 patients, we identified a list of differentially expressed genes which was significantly associated with prognosis in KIRC patients. Protein-protein interaction networks and functional enrichment analysis were both performed, indicating that these identified genes were related to the immune response. ConclusionsThe tumor microenvironment-related genes could serve as the potential biomarkers for KIRC.

scholarly journals Abnormal Expression and Prognostic Significance of EPB41L1 in Kidney Renal Clear Cell Carcinoma Based on Data Mining

2020 ◽  
Author(s):  
Taotao Liang ◽  
Siyao Sang ◽  
Qi Shao ◽  
Zhichao Deng ◽  
Ting Wang ◽  
...  
Keyword(s):  
Data Mining ◽  
Cell Adhesion ◽  
Cell Carcinoma ◽  
Cancer Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Renal Clear Cell Carcinoma

Abstract Background: EPB41L1 gene (erythrocyte membrane protein band 4.1 like 1) encodes the protein 4.1N, a member of 4.1 family, playing a vital role in cell adhesion and migration, which is associated with the malignant progression of various human cancers. However, the expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma (KIRC) remains to be investigated.Methods: In this study, we collected the mRNA expression of EPB41L1 in KIRC through the Oncomine platform, and used the HPA database to perform the pathological tissue immunohistochemistry in patients. Then, the sub-groups and prognosis of KIRC were performed by UALCAN and GEPIA web-tool, respectively. Further, the mutation of EPB41L1 in KIRC were analyzed by c-Bioportal. The co-expression genes of EPB41L1 in KIRC were displayed from the LinkedOmics database, and function enrichment analysis was used by LinkFinder module in LinkedOmics. Co-expression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules, both of them were visualized by Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in TCGA by using the UCSC Xena browser.Results: The results indicated that EPB41L1 was down-expressed in KIRC, leading to a poor prognosis. Moreover, there is a mutation in the FERM domain of EPB41L1, but it has no significant effect on the prognosis of KIRC. The co-expressed genes of EPB41L1 was associated with cell adhesion. Further analysis suggested that EPB41L1 and amyloid beta precursor protein (APP) were coordinated to regulated cancer cell adhesion, thereby increasing the incidence of cancer cell metastasis and tumor invasion.Conclusions: In summary, EPB41L1 is constantly down-expressed in KIRC tissues, resulting a poor prognosis. Therefore, we suggest that it can be an effective biomarker for the diagnosis of KIRC.

scholarly journals MicroRNA related prognosis biomarkers from high throughput sequencing data of kidney renal clear cell carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Minjiang Huang ◽  
Ti Zhang ◽  
Zhi-Yong Yao ◽  
Chaoqung Xing ◽  
Qingyi Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Prognostic Model ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Critical Role ◽  
Renal Clear Cell Carcinoma ◽  
Pathway Enrichment Analysis ◽  
Survival Status ◽  
Model Based

Abstract Background Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cell carcinoma which has the worst overall survival rate. Almost 30% of patients with localized cancers eventually develop to metastases despite of early surgical treatment carried out. MicroRNAs (miRNAs) play a critical role in human cancer initiation, progression, and prognosis. The aim of our study was to identify potential prognosis biomarkers to predict overall survival of KIRC. Methods All data were downloaded from an open access database The Cancer Genome Atlas. DESeq2 package in R was used to screening the differential expression miRNAs (DEMs) and genes (DEGs). RegParallel and Survival packages in R was used to analysis their relationships with the KIRC patients. David version 6.8 and STRING version 11 were used to take the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Results We found 2 DEGs (TIMP3 and HMGCS1) and 3 DEMs (hsa-miR-21-5p, hsa-miR-223-3p, and hsa-miR-365a-3p) could be prognosis biomarkers for the prediction of KIRC patients. The constructed prognostic model based on those 2 DEGs could effectively predict the survival status of KIRC. And the constructed prognostic model based on those 3 DEMs could effectively predict the survival status of KIRC in 3-year and 5-year. Conclusion The current study provided novel insights into the miRNA related mRNA network in KIRC and those 2 DEGs biomarkers and 3 DEMs biomarkers may be independent prognostic signatures in predicting the survival of KIRC patients.

scholarly journals Abnormal Expression and Prognosis Value of COG Complex Members in Kidney Renal Clear Cell Carcinoma (KIRC)

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Yanjun Zhang ◽  
Hui Lai ◽  
Bin Tang
Keyword(s):  
Cell Carcinoma ◽  
Mrna Expression ◽  
Membrane Trafficking ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Protein Glycosylation ◽  
Free Survival ◽  
Cog Complex

Kidney renal clear cell carcinoma (KIRC) is the most aggressive subtype of kidney tumours with poor prognosis as well as the increasing incidence rate in worldwide. The conserved oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein that controls membrane trafficking and protein glycosylation and plays vital roles in human disease including cancers. Therefore, to uncover the prognostic value of COG complex in KIRC, a series of databases, including UALCAN database, GEPIA database, and Kaplan-Meier plotter, were used to analyse the mRNA expression of COG complex subunits and their prognostic values in patients with KIRC in this study. Compared with normal counterparts, mRNA expression of six COG complex subunits was significantly downregulated in KIRC tissue in UALCAN database, while COG4 mRNA expression was significantly upregulated in KIRC tissue. Moreover, the survival analysis indicated that all members of COG complex subunits were closely related with the prognosis of KIRC patients, while COG1 and COG4 were significantly associated with unfavourable overall survival (OS), the rest of COG complex subunits were importantly correlated with favourable OS. Simultaneously, higher mRNA expression of COG3, COG6, and COG8 exhibits better progression-free survival (PFS) and disease-free survival (DFS) in KIRC patients. These results identified that COG complex subunits, especially COG3, COG6, and COG8, are potential prognostic biomarkers of KIRC patients and may offer effective and new strategies for more accurately diagnosing the patients with KIRC in advance.

scholarly journals Screening Novel Drug Candidates for Kidney Renal Clear Cell Carcinoma Treatment: A Study on Differentially Expressed Genes through the Connectivity Map Database

2021 ◽  
pp. 1-12
Author(s):  
Bin Gao ◽  
Lijuan Wang ◽  
Na Zhang ◽  
Miaomiao Han ◽  
Yubo Zhang ◽  
...  
Keyword(s):  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Enrichment Analysis ◽  
Renal Clear Cell Carcinoma ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Connectivity Map ◽  
Hub Genes ◽  
Pathway Enrichment ◽  
Drug Candidates

<b><i>Objective:</i></b> Kidney renal clear cell carcinoma (KIRC) is a common cancer with high morbidity and mortality in renal cancer. Thus, the transcriptome data of KIRC patients in The Cancer Genome Atlas (TCGA) database were analyzed and drug candidates for the treatment of KIRC were explored through the connectivity map (CMap) database. <b><i>Methods:</i></b> The transcriptome data of KIRC patients were downloaded from TCGA database, and KIRC-associated hub genes were screened out through differential analysis and protein-protein interaction (PPI) network analysis. Afterward, the CMap database was used to select drug candidates for KIRC treatment, and the drug-targeted genes were obtained through the STITCH database. A PPI network was constructed by combining drug-targeted genes with hub genes that affected the pathogenesis of KIRC to obtain final hub genes. Finally, combining hub genes and KIRC-associated hub genes, the pathways affected by drugs were explored by pathway enrichment analysis. <b><i>Results:</i></b> A total of 2,312 differentially expressed genes were found in patients, which were concentrated in immune cell activity, cytokine, and chemokine secretion pathways. Drug screening disclosed 5 drug candidates for KIRC treatment: fedratinib, Ly344864, geldanamycin, AS-605240, and luminespib. Based on drug-targeted genes and KIRC-associated hub genes, 16 hub genes were screened out. Pathway enrichment analysis revealed that drugs mainly affected pathways such as neuroactive ligand pathways, cell adhesion, and chemokines. <b><i>Conclusion:</i></b> The above results indicated that fedratinib, LY 344864, geldanamycin, AS-605240, and luminespib could be used as candidates for KIRC therapy. The findings from this study will make contributions to the treatment of KIRC in the future.

scholarly journals Inhibition of KIF20A by transcription factor IRF6 affects the progression of renal clear cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xinwei Ma ◽  
Xiaoqi Wang ◽  
Qian Dong ◽  
Hongquan Pang ◽  
Jianming Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Cell Carcinoma ◽  
Renal Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, whose incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, although there is yet no report on its expression in ccRCC. Methods The expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP databases. In addition, GEPIA database predicted the relationship between IRF6 and KIF20A expressions and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP assays. The specific effects of IRF6 on ccRCC cell proliferation, invasion and apoptosis were subsequently examined at both cellular level and animal level. Results The database predicted down-regulated IRF6 expression in renal carcinoma tissues and its correlation with poor prognosis. IRF6 overexpression inhibited cRCC cell proliferation, invasion and migration. In addition, up-regulated KIF20A expression in renal carcinoma tissues and its association with prognosis were also predicted. Interference with KIF20A inhibited the proliferation, invasion, and migration of ccRCC cells. Finally, we confirmed that KIF20A is a functional target of IRF6 and can partially reverse the effects of IRF6 on the proliferation, invasion and migration of ccRCC cells. Conclusion: Inhibition of KIF20A by transcription factor IRF6 affects cell proliferation, invasion and migration in renal clear cell carcinoma.

scholarly journals Identification and Validation of PIK3CA as a Marker Associated with Prognosis and Immune Infiltration in Renal Clear Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Ya Li ◽  
Chong Wang ◽  
Yang Gao ◽  
Liang Zhou
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Potential Biomarker

Background. Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy. The therapeutic strategies for advanced KIRC are very few, with only sunitinib being widely approved. Mutations in the PIK3CA gene can affect tumor cell proliferation, metastasis, and patients’ survival. Methods. Bioinformatics analysis was performed to explore the expression and clinical significance of PIK3CA in KIRC. Moreover, qRT-PCR was conducted to verify the result. Results. Subgroup analyses of KIRC tissue based on gender, tumor grade, and cancer stage indicated downregulation of PIK3CA mRNA expression. The KIRC patients with high PIK3CA expression indicated a better overall survival, progression-free survival, and disease-free survival. A predictive nomogram was constructed and demonstrated that the calibration plots for the 3-year and 5-year OS rates were predicted relatively well compared with an ideal model in the TCGA KIRC cohort. The validation study revealed that downregulation of PIK3CA in KIRC tissues and low PIK3CA expression had a poor overall survival with an AUC of 0.775 in the ROC curve. Moreover, Cox regression analysis revealed that PIK3CA expression and clinical stage were independent factors affecting the prognosis of KIRC patients. PIK3CA expression was found to be significantly associated with the abundance of immune cells and immune biomarker sets. PIK3CA and associated genes were found to be mainly associated with immune response and the JAK-STAT signaling pathway. Conclusion. We identified PIK3CA as a potential biomarker for prognosis correlated with immune infiltrates in KIRC. Further studies should focus on the functions of PIK3CA in KIRC carcinogenesis.

scholarly journals A Novel Defined Ferroptosis-Related Gene Signature for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma

2021 ◽  
Author(s):  
Ming Chen ◽  
Hui Liu ◽  
Ming-Hao Zhang ◽  
Li-Lin Wan ◽  
Nai-Peng Shi ◽  
...  
Keyword(s):  
Prediction Model ◽  
Cell Carcinoma ◽  
Risk Prediction ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Enrichment Analysis ◽  
Renal Clear Cell Carcinoma ◽  
Go Enrichment ◽  
Tumor Group ◽  
Go Enrichment Analysis

Abstract Objective: Currently, the mechanism of ferroptosis in the progression of kidney renal clear cell carcinoma (KIRC) is still unclear. This paper aims to explore the potential mechanism of ferroptosis-related genes in KIRC.Methods: Using KIRC chip data in Gene Expression Synthesis (GEO) database, the differentially expressed genes (DEGs) between normal and tumor group were screened in GSE168845, GSE105261 and GSE11151 by limma package. Ferroptosis-related DEGs were gained by the intersection of DEGs and ferroptosis-related genes, which from the FerrDb database. Gene ontology (GO) enrichment analysis of ferroptosis-related DEGs was carried out by gene set enrichment analysis (GSEA). Univariate and multivariate Cox risk regression model was used to screen and establish gene prognosis risk prediction model. For ferroptosis-related DEGs, targeted small molecules are predicted for the treatment of KIRC.Results: In GSE168845, GSE105261 and GSE11151, 2532 DEGs were screened from normal group and tumor group. And 149 ferroptosis-related genes were obtained from the FerrDb database. Through the intersection of DEGs and ferroptosis-related genes, 17 ferroptosis-related DEGs were obtained. GO enrichment analysis indicated that primary biological processes of 17 ferroptosis-related DEGs enrichment had iron ion binding, microvillus membrane and regulation of transcription from RNA polymerase II promoter in response to stress. Based on univariate and multivariate Cox regression analysis, the multivariate prognostic risk prediction model composed of three ferroptosis DEGs including MT1G, LAMP2 and MIOX was constructed. The results of patient risk score indicated that the prognosis with high score was worse than those with low score. Meanwhile, we found that the exprssion of MT1G, LAMP2 and MIOX were related with methylation and immune infiltration in KIRC. Terroptosis-gene interaction and terroptosis-miRNA coregulatory network of MT1G, LAMP2 and MIOX were collected by Network Analyst. Then, the ferroptosis-related prognosis nomogram, including age, gender, grade, TNM and risk score, was found to predict the overall survival (OS) of KIRC patients. Finally, according to ferroptosis related DEGs, the potential therapeutic effects of emetine, cephaeline,scoulerline, sanguinarine, cicloheximide, tolfenamic acid, phenoxybenzamine and calmidazolium were predicted in KIRC.Conclusion: The risk prediction models of MT1G, LAMP2 and MIOX can effectively predict the prognosis of patients with KIRC. And MT1G, LAMP2 and MIOX are related to methylation and immune infiltration in KIRC, which is expected to play a guiding role in the clinical treatment of KIRC. Targeted these three genes, potential therapeutic drugs of emetine, cephaeline,scoulerline, sanguinarine, cicloheximide, tolfenamic acid, phenoxybenzamine and calmidazolium were also predicted in KIRC.

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