Prognostic impact of immune gene expression signature and tumor infiltrating immune cells in localized clear cell renal cell carcinoma

The Identification of reliable Biomarkers able to predict the outcome after nephrectomy of patients with clear cell renal cell carcinoma (ccRCC) is an unmet need. The gene expression analysis in tumor tissues represents a promising tool for better stratification of ccRCC subtypes and patients’ evaluation. Methods: In our study we retrospectively analyzed using Next-Generation expression analysis (NanoString), the expression of a gene panel in tumor tissue from 46 consecutive patients treated with nephrectomy for non-metastatic ccRCC at two Italian Oncological Centres. Significant differences in expression levels of selected genes was sought. Additionally, we performed a univariate and a multivariate analysis on overall survival according to Cox regression model. Results: A 17-gene expression signature of patients with a recurrence-free survival (RFS) < 1 year (unfavorable genomic signature (UGS)) and of patients with a RFS > 5 years (favorable genomic signature (FGS)) was identified and resulted in being significantly correlated with overall survival of the patients included in this analysis (HR 51.37, p < 0.0001). Conclusions: The identified Genomic Signatures may serve as potential biomarkers for prognosis prediction of non-metastatic RCC and could drive both follow-up and treatment personalization in RCC management.

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The Immune-Related Gene HCST as a Novel Biomarker for the Diagnosis and Prognosis of Clear Cell Renal Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.630706 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yongying Zhou ◽

Xiao Wang ◽

Weibing Zhang ◽

Huiyong Liu ◽

Daoquan Liu ◽

...

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Immune Cells ◽

Renal Cell ◽

Clear Cell ◽

Signal Transducer ◽

Related Gene ◽

Cell Renal Cell Carcinoma ◽

Immune Related Gene

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that the immune-related gene (IRG) hematopoietic cell signal transducer (HCST) could provide guidance for the diagnosis, prognosis, and treatment of ccRCC. The RNA-seq data of ccRCC tissues were extracted from two databases: TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/). Corresponding clinical information was downloaded from TCGA. Immune-related gene data were extracted from the IMMPORT website (https://www.immport.org/). Differential analysis with R software (https://www.r-project.org/) was used to obtain a prognosis model of ccRCC IRGs. The differences were combined with the clinical data to assess the usefulness of the HCST as a prognostic biomarker. Based on data obtained from the Oncomine (https://www.oncomine.org/), Human Protein Atlas (https://www.proteinatlas.org/), and PubMed (https://pubmed.ncbi.nlm.nih.gov/) databases, the expression levels of the HCST in ccRCC, clinical-pathological indicators of relevance, and influence on prognosis were analyzed. Regulation of the HCST gene in ccRCC was assessed by gene set enrichment analysis (GSEA). In TCGA/GEO databases, the high HCST expression in tumor tissues was significantly correlated to the TMN stage, tumor grade, invasion depth, and lymphatic metastasis (p < 0.05). The overall survival (OS) of patients with high HCST gene expression was significantly lower than that of patients with low HCST gene expression (p < 0.001). Multivariate Cox regression analysis suggested that the HCST expression level [hazard ratio (HR) = 1.630, 95% confidence interval (CI) = 1.042–2.552], tumor cell grade (HR = 1.829, 95% CI = 1.115–3.001), and distant metastasis (HR = 2.634, 95%, CI = 1.562–4.442) were independent risk factors affecting the OS of ccRCC patients (all, p < 0.05). The GSEA study showed that there was significant enrichment in cell adhesion, tumorigenesis, and immune and inflammatory responses in HCST high expression samples. Hematopoietic cell signal transducer expression was closely associated with the levels of infiltrating immune cells around ccRCC tissues, especially dendritic cells (DCs). In conclusion, the present study suggested that the HCST was interrelated to the clinicopathology and poor prognosis of ccRCC. High HCST expression was also closely correlated with the levels of tumor-infiltrating immune cells, especially DCs.

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Molecular Characterization of Clear Cell Renal Cell Carcinoma Reveals Prognostic Significance of Epithelial-mesenchymal Transition Gene Expression Signature

European Urology Oncology ◽

10.1016/j.euo.2021.10.007 ◽

2021 ◽

Author(s):

Srinivas Nallandhighal ◽

Randy Vince ◽

Razeen Karim ◽

Skylar Groves ◽

Judith Stangl-Kremser ◽

...

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Epithelial Mesenchymal Transition ◽

Prognostic Significance ◽

Gene Expression Signature ◽

Cell Renal Cell Carcinoma ◽

Mesenchymal Transition

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A Specific Gene Expression Signature Characterizes Metastatic Potential in Clear Cell Renal Cell Carcinoma

The Journal of Urology ◽

10.1016/j.juro.2011.03.033 ◽

2011 ◽

Vol 186 (1) ◽

pp. 289-294 ◽

Cited By ~ 28

Author(s):

Jimsgene Sanjmyatav ◽

Thomas Steiner ◽

Heiko Wunderlich ◽

Julia Diegmann ◽

Mieczyslaw Gajda ◽

...

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Gene Expression Signature ◽

Metastatic Potential ◽

Specific Gene ◽

Cell Renal Cell Carcinoma ◽

Specific Gene Expression

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Neo-Fs Index: A Novel Immunohistochemical Biomarker Panel Predicts Survival and Response to Anti-Angiogenetic Agents in Clear Cell Renal Cell Carcinoma

Cancers ◽

10.3390/cancers13061199 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1199

Author(s):

Jisup Kim ◽

Jee-Young Park ◽

Su-Jin Shin ◽

Beom Jin Lim ◽

Heounjeong Go

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Plasmacytoid Dendritic Cell ◽

Cytolytic Activity ◽

Immune Gene ◽

Protein Markers ◽

Cell Renal Cell Carcinoma ◽

Frameshift Indels

Background: Frameshift indels have emerged as a predictor of immunotherapy response but were not evaluated yet to predict anti-angiogenetic agent (AAA) response or prognosis in clear cell renal cell carcinoma (ccRCC). Methods: Here, to develop biomarkers that predict survival and response to AAA, we evaluated the immunohistochemical expression of proteins whose genes frequently harbor frameshift indels in 638 ccRCC patients and correlated the individual and integrated markers with prognosis and AAA response. The mutational landscape was evaluated using targeted next-generation sequencing in 12 patients concerning protein markers. Immune gene signatures were retrieved from TCGA RNA seq data. Results: Five proteins (APC, NOTCH1, ARID1A, EYS, and filamin A) were independent adverse prognosticators and were incorporated into the Neo-fs index. Better overall, disease-specific and recurrence-free survival were observed with high Neo-fs index in univariate and multivariate survival analyses. Better AAA responses were observed with a high Neo-fs index, which reflected increased MHC class I, CD8+ T cell, cytolytic activity, and plasmacytoid dendritic cell signatures and decreased type II-IFN response signatures, as well as greater single-nucleotide variant (SNV) and indel counts. Conclusions: Neo-fs index, reflecting antitumor immune signature and more SNVs. and indels, is a powerful predictor of survival and AAA response in ccRCC.

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PD57-01 WHOLE-TRANSCRIPTOME SEQUENCING IDENTIFIED GENE EXPRESSION SIGNATURES ASSOCIATED WITH AGGRESSIVE CLEAR CELL RENAL CELL CARCINOMA

The Journal of Urology ◽

10.1016/j.juro.2018.02.2645 ◽

2018 ◽

Vol 199 (4S) ◽

Author(s):

Ken Batai ◽

Elliot Imler ◽

Michael Phung ◽

Robert Bell ◽

Aye Lwin ◽

...

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Transcriptome Sequencing ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Gene Expression Signatures ◽

Whole Transcriptome Sequencing ◽

Whole Transcriptome

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Systematic Analyses of The Role of Prognostic And Immunological of EIF3A, A Reader Protein, In Clear Cell Renal Cell Carcinoma

10.21203/rs.3.rs-696657/v1 ◽

2021 ◽

Author(s):

Yi Zhang ◽

Xiaoliang Hua ◽

Haoqiang Shi ◽

Li Zhang ◽

HaiBing Xiao ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

T Cells ◽

Cell Carcinoma ◽

Immune Cells ◽

Renal Cell ◽

Clear Cell ◽

Multivariate Analyses ◽

Enrichment Analysis ◽

Marker Genes ◽

Cell Renal Cell Carcinoma

Abstract Background: Eukaryotic initiation factor 3a, EIF3A, as a “reader” protein for RNA methylation, has been found to be related to promote tumorigenesis in different variety of cancers. The impaction of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be expounded. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between expression and immune infiltration.Methods: We collected 29 m6a related mRNA data and clinicopathological parameters from Cancer Genmoe Atlas (TCGA) database. Logistic regression analyses were used to analyze the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) were applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize forcefully independent factor in associated with overall survival (OS) and diseases free survival (DFS). Nomogram was aim at predicting the 1-, 3-and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to the potential function and related signaling pathways of EIF3A expression. To investigate EIF3A of co-expressed genes, we used LinkedOmics and its result was undertaken enrichment analysis. Simultaneously, to employ LinkedOmics and STRING dataset drew a conclusion that EIF3A co-expressed genes and visualized via Cytoscape. Finally, we evaluated that EIF3A expression correlated between with infiltration of immune cells and the expression of marker genes in ccRCC by Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA).Result: EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was connected with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with poor prognosis. The result of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that high expression was enriched in renal cell carcinoma pathway and so on. EIF3A expression was significantly positively correlated with B cells, CD8+T cells, CD4+T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most of marker genes of immune cells.Conclusions: EIF3A could serve as potential biomarkers for prognostic and diagnostic stratification factor for ccRCC and is related with immune cells infiltrates.

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