A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

Gremel, Gabriela; Djureinovic, Dijana; Niinivirta, Marjut; Laird, A. Douglas; Ljungqvist, Oscar; Johannesson, Henrik; Bergman, Julia; Edqvist, Perk-Henrik; Navani, Sanjay; Khan, Nazia; Patil, Tushar; Sivertsson, Åsa; Uhlén, Mathias; Harrison, David J.; Ullenhag, Gustav; Stewart, Grant D.; Pontén, Fredrik

doi:10.1186/s12885-016-3030-6

Cited by 29 publications

(25 citation statements)

References 26 publications

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“…However, we found a significant association of low CUBN gene expression with poor overall survival of ccRCC patients in the TCGA ccRCC dataset. In addition, this gene has already been identified as an independent prognostic marker for renal cell carcinoma at the protein level [18]. Interestingly, CUBN has been suggested as a predictive marker for the treatment of renal cancer patients with sunitinib and sorafenib [19].…”

Section: Discussionmentioning

confidence: 99%

RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes

Wach

Täubert

Weigelt

et al. 2019

Cancers

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Collecting duct carcinoma (CDC) is a rare renal cell carcinoma subtype with a very poor prognosis. There have been only a few studies on gene expression analysis in CDCs. We compared the gene expression profiles of two CDC cases with those of eight normal tissues of renal cell carcinoma patients. At a threshold of |log2fold-change| ≥1, 3349 genes were upregulated and 1947 genes were downregulated in CDCs compared to the normal samples. Pathway analysis of the deregulated genes revealed that cancer pathways and cell cycle pathways were most prominent in CDCs. The most upregulated gene was keratin 17, and the most downregulated gene was cubilin. Among the most downregulated genes were four solute carrier genes (SLC3A1, SLC9A3, SLC26A7, and SLC47A1). The strongest negative correlations between miRNAs and mRNAs were found between the downregulated miR-374b-5p and its upregulated target genes HIST1H3B, HK2, and SLC7A11 and between upregulated miR-26b-5p and its downregulated target genes PPARGC1A, ALDH6A1, and MARC2. An upregulation of HK2 and a downregulation of PPARGC1A, ALDH6A1, and MARC2 were observed at the protein level. Survival analysis of the cancer genome atlas (TCGA) dataset showed for the first time that low gene expression of MARC2, cubilin, and SLC47A1 and high gene expression of KRT17 are associated with poor overall survival in clear cell renal cell carcinoma patients. Altogether, we identified dysregulated protein-coding genes, potential miRNA-target interactions, and prognostic markers that could be associated with CDC.

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Section: Discussionmentioning

confidence: 99%

RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes

Wach

Täubert

Weigelt

et al. 2019

Cancers

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“…Among them, 80-90% patients die of clear cell renal cell carcinoma (ccRCC) which has distinctive features such as local invasion, distant metastasis and high lethal rate [2]. Thus, the prognosis of patients with ccRCC is worse and the incidence of ccRCC is gradually increasing with a mortality rate about 40% [3]. At present, the main treatment of RCC is surgical treatment.…”

Section: Introductionmentioning

confidence: 99%

Long intergenic non-coding RNA 1939 eliminates proliferation and migration of human renal cell carcinoma (RCC) cells by down-regulation of miR-154

Zhang

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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Renal carcinoma (RCC) is widely accepted as a malignant tumour of urinary system. Long intergenic non-coding RNA 1939 (LINC01939) is a novel lncRNA which was found to be down-regulated in RCC. Thus, we set out to explore the effect and regulation mechanism of LINC01939 in RCC. LINC01939 and miR-154 in RCC tissues and cell lines were detected using qRT-PCR assay. To examine cellular viability of ACHN and CAKI-1 cells, cell counting kit-8 (CCK-8) assay was exploited here. Flow cytometric analysis was conducted to examine apoptosis. Cell mobility was valued through wound healing assays. Western blotting was applied for examination of proteins related to proliferation, apoptosis, migration and Wnt/ b-catenin/Notch. LINC01939 was down-regulated in RCC tissues. LINC01939 overexpression impeded proliferation and migration, and induced apoptosis. Further study found that the overexpression of LINC01939 strongly suppressed miR-154 expression. Then, the inhibiting effect of overexpressed LINC01939 on proliferation and mobility and the promoting role of LINC01939 in apoptosis were abolished by the combination of miR-154 mimic. Finally, we found that overexpressed LINC01939 inactivated Wnt/b-catenin and Notch through suppressing miR-154. Up-regulation of LINC01939 inhibited proliferation and migration of RCC cells by down-regulating miR-154.

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“… 2 The most common subtype of RCC is clear cell renal cell carcinoma (ccRCC), which is associated with high morbidity and poor prognosis. 3 …”

Section: Introductionmentioning

confidence: 99%

Identification and validation of a four-miRNA(miRNA-21-5p, miRNA-9-5p, miR-149-5p, and miRNA-30b-5p) prognosis signature in clear cell renal cell carcinoma

Xie¹,

Lv²,

Liu³

et al. 2018

CMAR

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PurposeClear cell renal cell carcinoma (ccRCC) is one of the most common cancers with high mortality worldwide. However, biomarkers for predicting prognosis in ccRCC are limited. In this study, we attempted to identify potential prognostic biomarkers of ccRCC.MethodsClinical information and the preprocessed ccRCC mature miRNA expression profiles in The Cancer Genome Atlas database were downloaded from UCSC Xena. The miRNAs differentially expressed between ccRCCs and matched normal tissues were analyzed using the “limma” package. A miRNA-based signature was constructed using the multivariate Cox regression model with prognosis index (PI) formula. Patients with ccRCC were divided into low-risk and high-risk subgroups according to median PI. The survival times were compared between the two groups using Kaplan–Meier analysis with log-rank test. The training set was used to construct a miRNA-based signature for predicting prognosis. The test set was used to verify the signature. Target gene prediction and functional enrichment analysis of the four miRNAs were performed using miRNet.ResultsWe identified four miRNAs, miRNA-21-5p, miRNA-9-5p, miR-149-5p, and miRNA-30b-5p, as independent prognostic indicators. Next, we used these four miRNAs to construct a four-miRNA PI for each patient. Results revealed that patients in the high-risk group (n=119) had significantly shorter survival time than those in the low-risk group (n=118) (high-risk/low-risk group log-rank P=0.000). This four-miRNA signature is an independent prognostic factor compared with routine clinicopathological features in the test set. These miRNAs targeted 1,634 genes, and a miRNA-target gene network was constructed using miRNet. The target genes of these four miRNAs were involved in various pathways related to cancer.ConclusionOur observations suggest that the four-miRNA signature correlated with the survival of patients with ccRCC and can be used as a prognostic biomarker of ccRCC.

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A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

Cited by 29 publications

References 26 publications

RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes

RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes

Long intergenic non-coding RNA 1939 eliminates proliferation and migration of human renal cell carcinoma (RCC) cells by down-regulation of miR-154

Identification and validation of a four-miRNA(miRNA-21-5p, miRNA-9-5p, miR-149-5p, and miRNA-30b-5p) prognosis signature in clear cell renal cell carcinoma

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