Low expression of ferritinophagy-related NCOA4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma

Abstract Background Clear cell renal cell carcinoma is susceptible to ferroptosis, and immunotherapy is recently recommended as a priority for the initial treatment of metastatic clear cell renal carcinoma. Increased ferroptosis and immune activation can synergistically reinforce each other in killing cancer cells. NCOA4 depletion can eliminate iron accumulation and thus weaken ferroptosis. Here, we aim to identify and validate the association between NCOA4 expression, clinicopathologic characteristics, and overall survival in ccRCC by using The Cancer Genome Atlas and Gene Expression Omnibus databases. We further analyze the interacted proteins of NCOA4 and infiltrated immune cells via TIMER and GEPIA databases. Methods NCOA4 expression in clear cell renal carcinoma (ccRCC) tissues and normal adjacent tissues in The Cancer Genome Atlas (TCGA) data were primarily screened, and further validated in another independent cohort from the gene expression omnibus (GEO) database and human protein atlas. The relationships of NCOA4 expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which NCOA4 interacted were also built using the online STRING website. Meanwhile, we use TIMER and GEPIA databases to investigate the relationships between NCOA4 expression and infiltrated immune cells and their corresponding gene marker sets. Results Contrast to normal tissue, NCOA4 expression was lower in ccRCC tumor tissue(p < 0.05). Lower NCOA4 expression was closely associated with high-grade malignancy and advanced TNM stage. Univariate and multivariate analysis indicated the overall survival of ccRCC cases with low NCOA4 level is shorter than those of patients with high NCOA4 expression (p < 0.05). FTL and FTH1 were the important proteins interacting with NCOA4. ccRCC with NCOA4 deficiency presented the paucity of infiltrated immune cells and their matching marker sets, including CD8+ T cells. Conclusion Deficient NCOA4 expression was related to disease progression and poor prognosis, as well as impaired infiltration of immune cells in ccRCC.

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MP71-08 SELECT CONCURRENT CHROMOSOME 3P MUTATIONS PREDICT WORSE OVERALL AND RECURRENCE-FREE SURVIVAL IN CLEAR CELL RENAL CARCINOMA IN THE CANCER GENOME ATLAS

The Journal of Urology ◽

10.1016/j.juro.2016.02.1454 ◽

2016 ◽

Vol 195 (4S) ◽

Author(s):

Christopher Keith ◽

John Petros ◽

Michael Rossi ◽

Rebecca Arnold

Keyword(s):

Renal Carcinoma ◽

Clear Cell ◽

The Cancer Genome Atlas ◽

Recurrence Free Survival ◽

Clear Cell Renal Carcinoma ◽

Free Survival ◽

Chromosome 3P ◽

Cell Renal Carcinoma ◽

Cancer Genome Atlas ◽

Genome Atlas

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High expression level of MMP9 is associated with poor prognosis in patients with clear cell renal carcinoma

PeerJ ◽

10.7717/peerj.5050 ◽

2018 ◽

Vol 6 ◽

pp. e5050 ◽

Cited By ~ 10

Author(s):

Haitao Niu ◽

Feng Li ◽

Qingshui Wang ◽

Zhoujie Ye ◽

Qi Chen ◽

...

Keyword(s):

Renal Carcinoma ◽

Clear Cell ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Mrna Levels ◽

Clear Cell Renal Carcinoma ◽

Protein Levels ◽

Mmp9 Expression ◽

Cell Renal Carcinoma

Matrix metallopeptidase 9 (MMP9) was found to be associated with tumor aggressiveness. In this study, we focused on the correlation between MMP9 expression and clear cell renal carcinoma (ccRCC). Through the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) database and immunohistochemical (IHC) staining, we observed that compared with adjacent normal renal tissues, in ccRCC tissues the mRNA and protein levels of MMP9 were enhanced, and the mRNA levels of GTP-binding protein smg p21B(RAP1B), B rapidly accelerated fibrosarcoma (RAF), methyl ethyl ketone2 (MEK2), extracellular regulated protein kinases1 (ERK1), ERK2, v-ets avian erythroblastosis virus E26 oncogene homolog1 (ETS1) and ETS2 also increased. The Kaplan–Meier survival analysis suggested that high MMP9 expression was an unfavorable prognostic biomarker for ccRCC patients. Our results indicated that the increased expression level of MMP9 in ccRCC may be due to the activation of the Mitogen-activated protein kinases (MAPK)/ERK signaling pathway, and MMP9 may be an attractive target for ccRCC therapy.

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Comprehensive analysis of ceRNA networks to determine genes related to prognosis, overall survival, and immune infiltration in clear cell renal carcinoma

Computers in Biology and Medicine ◽

10.1016/j.compbiomed.2021.105043 ◽

2021 ◽

pp. 105043

Author(s):

Ghanbar Mahmoodi Chalbatani ◽

Seyed Ali Momeni ◽

Mohammad Hosein Mohammadi Hadloo ◽

Zhina Karimi ◽

Morteza Hadizadeh ◽

...

Keyword(s):

Overall Survival ◽

Renal Carcinoma ◽

Clear Cell ◽

Comprehensive Analysis ◽

Clear Cell Renal Carcinoma ◽

Immune Infiltration ◽

Cell Renal Carcinoma

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267 LOSS OF EPITHELIAL CELL ADHESION MOLECULE (EPCAM) IS ASSOCIATED WITH POOR OVERALL SURVIVAL IN CLEAR CELL RENAL CARCINOMA (CCRCC) - RESULTS OF A LARGE TMA-BASED ANALYSIS

European Urology Supplements ◽

10.1016/s1569-9056(11)60265-0 ◽

2011 ◽

Vol 10 (2) ◽

pp. 104-105

Author(s):

C. Eichelberg ◽

F.K. Chun ◽

S. Minner ◽

T. Schlomm ◽

H. Moch ◽

...

Keyword(s):

Overall Survival ◽

Cell Adhesion ◽

Epithelial Cell ◽

Cell Adhesion Molecule ◽

Renal Carcinoma ◽

Clear Cell ◽

Epithelial Cell Adhesion Molecule ◽

Clear Cell Renal Carcinoma ◽

Poor Overall Survival ◽

Cell Renal Carcinoma

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The role of miR-92b in cholangiocarcinoma patients

The International Journal of Biological Markers ◽

10.1177/1724600817751524 ◽

2018 ◽

Vol 33 (3) ◽

pp. 293-300 ◽

Cited By ~ 3

Author(s):

Min-hang Zhou ◽

Hong-wei Zhou ◽

Mo Liu ◽

Jun-zhong Sun

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Gene Expression Omnibus ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Positive Regulation ◽

Cancer Genome Atlas ◽

High Level ◽

Genome Atlas

Purpose: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. Methods: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan–Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. Results: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.

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