Molecular characterization of clear cell renal cell carcinoma identifies <scp>CSNK</scp>2A1, <scp>SPP</scp>1 and <scp>DEFB</scp>1 as promising novel prognostic markers

Rabjerg, Maj; Bjerregaard, Henriette; Halekoh, Ulrich; Jensen, Boye L.; Walter, Steen; Marcussen, Niels

doi:10.1111/apm.12519

Cited by 41 publications

(47 citation statements)

References 55 publications

(65 reference statements)

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“…DEFB1 encodes b-defensin, which belongs to a family of antimicrobial peptides produced by white blood cells and epithelial cells. Rabjerg and colleagues (40) suggested that DEFB1 might be a tumor suppressor gene, but our results revealed that high expression of this gene predicted a worse prognosis with very weak significance (P ¼ 4.99eÀ2; HR ¼ 1.41, and 95% confidence interval ¼ 1.00-1.98). EDNRB is a member of the endothelin axis, and TSPAN7 is a member of the transmembrane 4 superfamily.…”

Section: Lasso-cox Risk Index Is Independent Of Known Prognostic Factorscontrasting

confidence: 67%

“…Using univariate and multivariate Cox proportional hazards analysis, we performed a comprehensive comparison between the lasso-Cox risk index and other known prognostic biomarkers, including two clinical variables, grade (G1þG2 vs. G3þG4), stage (IþII vs. IIIþIV), six gene expression signatures (39,40), CSNK2A1, SPP1, DEFB1, PECAM1, EDNRB, TSPAN7, and five somatic mutation genes (26,(41)(42)(43)(44)(45)(46), VHL, PBRM1, BAP1, SETD2, TP53. Patient subtyping for gene expression signatures was carried out by using the median as cut-off point.…”

Section: Lasso-cox Risk Index Is Independent Of Known Prognostic Factorsmentioning

confidence: 99%

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Integrative Analysis of Histopathological Images and Genomic Data Predicts Clear Cell Renal Cell Carcinoma Prognosis

et al. 2017

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In cancer, both histopathologic images and genomic signatures are used for diagnosis, prognosis, and subtyping. However, combining histopathologic images with genomic data for predicting prognosis, as well as the relationships between them, has rarely been explored. In this study, we present an integrative genomics framework for constructing a prognostic model for clear cell renal cell carcinoma. We used patient data from The Cancer Genome Atlas (n ¼ 410), extracting hundreds of cellular morphologic features from digitized whole-slide images and eigengenes from functional genomics data to predict patient outcome. The risk index generated by our model correlated strongly with survival, outperforming predictions based on considering morphologic features or eigengenes separately. The predicted risk index also effectively stratified patients in early-stage (stage I and stage II) tumors, whereas no significant survival difference was observed using staging alone. The prognostic value of our model was independent of other known clinical and molecular prognostic factors for patients with clear cell renal cell carcinoma. Overall, this workflow and the shared software code provide building blocks for applying similar approaches in other cancers. Cancer Res; 77(21); e91-100. Ó2017 AACR.

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Section: Lasso-cox Risk Index Is Independent Of Known Prognostic Factorscontrasting

confidence: 67%

Section: Lasso-cox Risk Index Is Independent Of Known Prognostic Factorsmentioning

confidence: 99%

Integrative Analysis of Histopathological Images and Genomic Data Predicts Clear Cell Renal Cell Carcinoma Prognosis

et al. 2017

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“…For example, in Bae JS's study, CSNK2A1 was found to participate in the progression of breast carcinoma and to indicate poorer patient survival ( 77 ). In addition, Rabjerg et al ( 78 ) identified CSNK2A1 as a promising novel prognostic biomarker in clear cell renal carcinoma. Furthermore, CSNK2A1 has also been found to be involved in ovarian cancer ( 79 ), oral cancer ( 80 ), prostate cancer ( 81 , 82 ) and pancreatic cancer ( 83 ).…”

Section: Discussionmentioning

confidence: 99%

A meta‑analysis and bioinformatics exploration of the diagnostic value and molecular mechanism of miR‑193a‑5p in lung cancer

et al. 2018

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Lung cancer is a leading cause of mortality worldwide and despite recent improvements in lung cancer treatments patient mortality remains high. miR-193a-5p serves a crucial role in the initiation and development of cancer; it is necessary to understand the underlying molecular mechanisms of miR-193a-5p in lung cancer, which may enable the development of improved clinical diagnoses and therapies. The present study investigated the diagnostic value of peripheral blood and tissue miR-193a-5p expression using a microarray meta-analysis. Peripheral blood miR-193a-5p was revealed to be upregulated in patients with lung cancer. The pooled area under the curve (AUC) was 0.67, with a sensitivity and specificity of 0.74 and 0.56, respectively. Conversely, the peripheral tissue miR-193a-5p expression in patients with lung cancer was significantly downregulated. The pooled AUC was 0.83, and the sensitivity and specificity were 0.65 and 0.89, respectively. Through bioinformatics analysis, three Kyoto Encyclopedia of Genes and Genomes (KEGG) terms, pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway, were identified as associated with miR-193a-5p in lung cancer. In addition, in lung cancer, six key miR-193a-5p target genes, receptor tyrosine-protein kinase erbB-2 (ERBB2), nuclear cap-binding protein subunit 2 (NCBP2), collagen α-1(I) chain (COL1A1), roprotein convertase subtilisin/kexin type 9 (PCSK9), casein kinase II subunit α (CSNK2A1) and nucleolar transcription factor 1 (UBTF), were identified, five of which were significantly upregulated (ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF). The protein expression of ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF was also upregulated. NCBP2 and CSNK2A1 were negatively correlated with miR-193a-5p. The results demonstrated that miR-193a-5p exhibited opposite expression patterns in peripheral blood and tissue. Upregulated peripheral blood miR-193a-5p and downregulated tissue miR-193a-5p may be promising diagnostic biomarkers in lung cancer. In addition, the KEGG terms pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway may suggest which pathways serve vital roles in lung cancer by regulating miR-193a-5p. In addition, six genes, ERBB2, COL1A1, PCSK9, UBTF and particularly NCBP2 and CSNK2A1, may be key target genes of miR-193a-5p in lung cancer.

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“…A study based on gastric cancer cell lines indicated that the elevated expression of SPP1 is a critical determinant of poor prognosis and that OPN expression could help to predict the risk of hematogenous metastasis [28]. In addition, in a recent study, SPP1 was observed to be a novel prognostic marker for clear cell renal cell carcinoma [29]. Previous research concerning esophageal squamous cell carcinoma has also suggested that the elevated expression of SPP1 in tumor tissues was associated with poor prognosis [30].…”

Section: Zhuo Et Al: Tissue-specific Biomarkers For Gc Prognosismentioning

confidence: 99%

Elevated THBS2, COL1A2, and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis

Zhuo

Zhuang

et al. 2016

Cell Physiol Biochem

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Background/Aims:Gastric cancer (GC) is an important health problem. Classification based on molecular subtypes may help to determine the prognosis of patients with GC. Tumor invasion and metastasis are important factors affecting the prognosis of cancer. We aimed to identify genes related to tumor invasion and metastasis, which may serve as indicators of good GC prognosis. Methods:Tumor tissues and adjacent normal tissues were collected from 105 patients with primary GC who were treated by undergoing radical surgery. Samples were used for tissue microarray analysis. Identified genes with altered expression were further analyzed using the Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The expression levels of THBS2, COL1A2 and SPP1 were analyzed by RT-PCR, western blot and immunohistochemistry. The overall survival curves of patients with high and low expression of each gene of interest were plotted and compared. Results:Forty-three genes were identified. THBS2, COL1A2 and SPP1 were selected for further analysis. Altered expression levels of THBS2, COL1A2 and SPP1 in tumor tissues were confirmed. Patients with low THBS2 expression had a better prognosis; the expression of COL1A2 and SPP1 might not affect the prognosis of patients with GC. Conclusion:THBS2, but not COL1A2 and SPP1, may serve as an indicator of GC prognosis.

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Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers

Cited by 41 publications

References 55 publications

Integrative Analysis of Histopathological Images and Genomic Data Predicts Clear Cell Renal Cell Carcinoma Prognosis

Integrative Analysis of Histopathological Images and Genomic Data Predicts Clear Cell Renal Cell Carcinoma Prognosis

A meta‑analysis and bioinformatics exploration of the diagnostic value and molecular mechanism of miR‑193a‑5p in lung cancer

Elevated THBS2, COL1A2, and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis

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