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 High PON1 Expression Predicts Poor Prognosis In Kidney Renal Clear Cell Carcinoma

2021 ◽  
Author(s):  
Chenxia Jiang ◽  
Xinyu Zhang ◽  
Xiaoyan Li ◽  
Jia Li ◽  
Hua Huang
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Independent Prognostic Factor ◽  
Cox Regression Analysis

Abstract Background: Relevant study had demonstrated that Paraoxonase-1 (PON1) had relationship with occurrence and development of tumors which suggested that PON1 was a key gene in promoting tumor progression. However, the relationship between PON1 and Kidney renal clear cell carcinoma (KIRC) is still unclear so far. Methods: We downloaded relevant data about KIRC from TCGA dataset and compared it with normal renal tissues. Immunohistochemistry (IHC) was applied to analyze the expression of PON1. Univariate cox regression analysis and multivariate cox regression analysis were also utilized to analyze independent factors associated with prognosis. Gene set enrichment analysis was conducted to find the signaling pathways of PON1 in KIRC. Finally, we also investigated whether PON1 had relationship with immunity. Results: As shown in results, PON1 expression was decreased in KIRC compared with adjacent paracancer tissues. Immunohistochemistry (IHC) was utilized to find the expression of PON1. After survival analysis, the high expression of PON1 was significantly related to overall survival (P<0.001). Univariate/Multivariate cox regression analysis both revealed that PON1 could serve as an independent prognostic factor. To analyze overall survival (OS) of patients with KIRC, nomogram was developed. GSEA revealed that PON1 was correlated with homologous recombination. Besides, PON1 had few relationships with immunity. Conclusions: Our results revealed that PON1 could serve as an independent prognostic factor for KIRC, providing a novel target for KIRC future treatments.

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 a Prognostic Risk Signature of Kidney Renal Clear Cell Carcinoma Based on Regulating the Immune Response Pathway Exploration

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Guangzhen Wu ◽  
Yingkun Xu ◽  
Chenglin Han ◽  
Zilong Wang ◽  
Jiayi Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Carcinoma ◽  
Sensitivity And Specificity ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Lasso Regression ◽  
Regression Curve ◽  
Cox Regression Analysis

Purpose. To construct a survival model for predicting the prognosis of patients with kidney renal clear cell carcinoma (KIRC) based on gene expression related to immune response regulation. Materials and Methods. KIRC mRNA sequencing data and patient clinical data were downloaded from the TCGA database. The pathways and genes involved in the regulation of the immune response were identified from the GSEA database. A single factor Cox analysis was used to determine the association of mRNA in relation to patient prognosis P < 0.05 . The prognostic risk model was further established using the LASSO regression curve. The survival prognosis model was constructed, and the sensitivity and specificity of the model were evaluated using the ROC curve. Results. Compared with normal kidney tissues, there were 28 dysregulated mRNA expressions in KIRC tissues P < 0.05 . Univariate Cox regression analysis revealed that 12 mRNAs were related to the prognosis of patients with renal cell carcinoma. The LASSO regression curve drew a risk signature consisting of six genes: TRAF6, FYN, IKBKG, LAT2, C2, IL4, EREG, TRAF2, and IL12A. The five-year ROC area analysis (AUC) showed that the model has good sensitivity and specificity (AUC >0.712). Conclusion. We constructed a risk prediction model based on the regulated immune response-related genes, which can effectively predict the survival of patients with KIRC.

scholarly journals Angiogenesis Pathway in Kidney Renal Clear Cell Carcinoma and Its Prognostic Value for Cancer Risk Prediction

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiangyu Che ◽  
Wenyan Su ◽  
Xiaowei Li ◽  
Nana Liu ◽  
Qifei Wang ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Treatment Plan ◽  
Renal Clear Cell Carcinoma ◽  
Targeted Drugs ◽  
Cox Regression Analysis ◽  
Cluster 2 ◽  
Angiogenesis Pathway

Angiogenesis, a process highly regulated by pro-angiogenic and anti-angiogenic factors, is disrupted and dysregulated in cancer. Despite the increased clinical use of angiogenesis inhibitors in cancer therapy, most molecularly targeted drugs have been less effective than expected. Therefore, an in-depth exploration of the angiogenesis pathway is warranted. In this study, the expression of angiogenesis-related genes in various cancers was explored using The Cancer Genome Atlas datasets, whereupon it was found that most of them were protective genes in the patients with kidney renal clear cell carcinoma (KIRC). We divided the samples from the KIRC dataset into three clusters according to the mRNA expression levels of these genes, with the enrichment scores being in the order of Cluster 2 (upregulated expression) &gt; Cluster 3 (normal expression) &gt; Cluster 1 (downregulated expression). The survival curves plotted for the three clusters revealed that the patients in Cluster 2 had the highest overall survival rates. Via a sensitivity analysis of the drugs listed on the Genomics of Drug Sensitivity in Cancer database, we generated IC50 estimates for 12 commonly used molecularly targeted drugs for KIRC in the three clusters, which can provide a more personalized treatment plan for the patients according to angiogenesis-related gene expression. Subsequently, we investigated the correlation between the angiogenesis pathway and classical cancer-related genes as well as that between the angiogenesis score and immune cell infiltration. Finally, we used the least absolute shrinkage and selection operator (LASSO)–Cox regression analysis to construct a risk score model for predicting the survival of patients with KIRC. According to the areas under the receiver operating characteristic (ROC) curves, this new survival model based on the angiogenesis-related genes had high prognostic prediction value. Our results should provide new avenues for the clinical diagnosis and treatment of patients with KIRC.

scholarly journals Comprehensive analysis of lncRNA biomarkers in kidney renal clear cell carcinoma by lncRNA-mediated ceRNA network

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252452
Author(s):  
Ke Gong ◽  
Ting Xie ◽  
Yong Luo ◽  
Hui Guo ◽  
Jinlan Chen ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Regression Analysis ◽  
Cerna Network

Introduction Kidney renal clear cell carcinoma (KIRC) has a high incidence globally, and its pathogenesis remains unclear. Long non-coding RNA (lncRNA), as a molecular sponge, participates in the regulation of competitive endogenous RNA (ceRNA). We aimed to construct a ceRNA network and screened out possible lncRNAs to predict KIRC prognosis. Material and methods All KIRC data were downloaded from the TCGA database and screened to find the possible target lncRNA; a ceRNA network was designed. Next, GO functional enrichment and KEGG pathway of differentially expressed mRNA related to lncRNA were performed. We used Kaplan-Meier curve analysis to predict the survival of these RNAs. We used Cox regression analysis to construct a model to predict KIRC prognosis. Results In the KIRC datasets, 1457 lncRNA, 54 miRNA and 2307 mRNA were screened out. The constructed ceRNA network contained 81 lncRNAs, nine miRNAs, and 17 mRNAs differentially expressed in KIRC. Survival analysis of all differentially expressed RNAs showed that 21 lncRNAs, four miRNAs, and two mRNAs were related to the overall survival rate. Cox regression analysis was performed again, and we found that eight lncRNAs were related to prognosis and used to construct predictive models. Three lnRNAs from independent samples were meaningful. Conclusion The construction of ceRNA network was involved in the process and transfer of KIRC, and three lncRNAs may be potential targets for predicting KIRC prognosis.

scholarly journals Expression of BAG1 is associated with prognosis in kidney renal clear cell carcinoma based on bioinformatics

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hongrong Wu ◽  
Minjing Liu ◽  
Yuejun He ◽  
Guozhao Meng ◽  
Wanbei Guo ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Neoadjuvant Treatment ◽  
Renal Clear Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Low Expression

Abstract Background BCL2 associated Athano-Gene 1 (BAG1) has been described to be involved in the development and progression of cancer. But the role of BAG1 in kidney renal clear cell carcinoma (KIRC) has remained largely unknown. Methods We performed bioinformatic analysis of data from TCGA and GEO dataset. The role of BAG1 in KIRC was explored by Logistic and Cox regression model. The molecular mechanisms of BAG1 was revealed by GSEA. Results The current study found that the KIRC tumor samples have a low level of BAG1 mRNA expression compared to the matched normal tissues based on TCGA data and GEO databases. Low expression of BAG1 in KIRC was significantly associated with Sex, clinical pathological stage, tumor-node-metastasis (TNM) stage, hemoglobin levels, cancer status and history of neoadjuvant treatment. Kaplan-Meier survival analysis indicated that KIRC patients with BAG1 high expression have a longer survival time than those with BAG1 low expression (p < 0.000). Cox regression analysis showed that BAG1 remained independently associated with overall survival, with a hazard ratio (HR) of 1.75(CI:1.05–2.90; p = 0.029). GSEA indicated that the signaling pathways including fatty acid metabolism and oxidative phosphorylation were differentially enriched in high BAG1 expression phenotype. Conclusions These findings suggested that BAG1 expression may act as a potential favorable prognostic marker and challenging therapeutic target.

scholarly journals A Five-Gene Signature Predicts Prognosis in Patients with Kidney Renal Clear Cell Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yueping Zhan ◽  
Wenna Guo ◽  
Ying Zhang ◽  
Qiang Wang ◽  
Xin-jian Xu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Clinical Information ◽  
Gene Signature ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Tcga Dataset

Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers with high mortality all over the world. Many studies have proposed that genes could be used to predict prognosis in KIRC. In this study, RNA expression data from next-generation sequencing and clinical information of 523 patients downloaded from The Cancer Genome Atlas (TCGA) dataset were analyzed in order to identify the relationship between gene expression level and the prognosis of KIRC patients. A set of five genes that significantly associated with overall survival time was identified and a model containing these five genes was constructed by Cox regression analysis. By Kaplan-Meier and Receiver Operating Characteristic (ROC) analysis, we confirmed that the model had good sensitivity and specificity. In summary, expression of the five-gene model is associated with the prognosis outcomes of KIRC patients, and it may have an important clinical significance.

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.

GALNT14 expression in renal clear cell carcinoma and its effect on prognosis

2021 ◽  
Author(s):  
Yuqin Wei ◽  
Fan Wu ◽  
Shengfeng Zhang ◽  
Yanlin Tan ◽  
Qunying Wu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Regulatory Pathways ◽  
Cox Analysis ◽  
The Relationship

Abstract Background The expression of GALNT14 in kidney renal clear cell carcinoma (KIRC) and its clinical significance remains unknown. Methods The KIRC data expressed by GALNT14 was downloaded from The Cancer Genome Atlas (TCGA) database. The expression of GALNT14 was analyzed by R software, Perl software and online analysis database. The relationship between GALNT14 expression and clinicopathological features in KIRC was analyzed by univariate, multivariate Cox regression and some databases. Gene Expression Profling Interactive Analysis (GEPIA), Starbase v3.0, UALCAN, and Kaplan-Meier were used to analyze the relationship between GALNT14 expression and overall survival (OS) in KIRC. UALCAN detects the expression of GALNT14 methylation in KIRC. Linkedomics and Genemania were used to analyze the gene co-expression of GALNT14. Gene Set Enrichment Analysis (GSEA) was performed to search for potential regulatory pathways. Results We found that GALNT14 was overexpressed in KIRC (p=1.433e-25). Patients with high GALNT14 expression in KIRC had a better prognosis than patients with low GALNT14 expression (p=0.008). In addition, high GALNT14 expression in KIRC was significantly associated with low T stage and positive OS (p<0.05). Univariate Cox analysis showed that GALNT14 was positively correlated with OS (p<0.001). Multivariate Cox analysis showed that GALNT14 was associated with OS (p<0.001), age (p=0.01) and histological grade (p=0.02). GALNT14 methylation is low expressed in KIRC (p<0.001). GSEA analysis showed that GALNT14 was enriched in histidine metabolism, peroxisome, and renin-angiotensin system pathways. Conclusion GALNT14 can be used as an independent prognostic factor for renal clear cell carcinoma and a potential target for clinical diagnosis and treatment of KIRC.

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