Dataset Information

High expression of Aldolase A predicts poor survival in patients with clear-cell renal cell carcinoma.

ABSTRACT: BACKGROUND:Aldolase A (ALDOA) is a glycolytic enzyme that drives the glycolytic metabolic pathway in mammalian cells. The overexpression of ALDOA was observed in a variety of cancers including clear-cell renal cell carcinoma (ccRCC). However, little was known about the clinicopathological significance and prognostic value of ALDOA in ccRCC patients. METHODS:The expression of ALDOA was detected using immunohistochemical staining in 162 formalin-fixed, paraffin-embedded ccRCC sections. Prognostic outcomes correlated with ALDOA were examined using Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS:In patients with ccRCC, increased cytoplasmic ALDOA expression was positively associated with tumor size (P=0.021), TNM stages (P=0.034), lymph node metastasis (P=0.020), and overall survival (OS) (P<0.001). Kaplan-Meier analysis showed that high cytoplasmic expression of ALDOA was associated with a statistically significant lower OS (P<0.001). Multivariate analysis demonstrated that ALDOA expression was an independent and significant prognostic factor (HR =3.561, 95% CI =1.715-7.396, P=0.001). ALDOA expression was not associated with significant prognostic deference in the subgroups of TNM stage I patients or pT1 patients. CONCLUSION:Our results suggest that ALDOA expression is an independent prognostic factor for OS in patients with ccRCC.

SUBMITTER: Na N

PROVIDER: S-EPMC5338975 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High expression of Aldolase A predicts poor survival in patients with clear-cell renal cell carcinoma.

Na Ning N Li Heng H Xu Chengfang C Miao Bin B Hong Liangqing L Huang Zhengyu Z Jiang Qiu Q

Therapeutics and clinical risk management 20170227

<h4>Background</h4>Aldolase A (ALDOA) is a glycolytic enzyme that drives the glycolytic metabolic pathway in mammalian cells. The overexpression of ALDOA was observed in a variety of cancers including clear-cell renal cell carcinoma (ccRCC). However, little was known about the clinicopathological significance and prognostic value of ALDOA in ccRCC patients.<h4>Methods</h4>The expression of ALDOA was detected using immunohistochemical staining in 162 formalin-fixed, paraffin-embedded ccRCC sectio ...[more]

PMID: 28280347

Similar Datasets

Project description:BackgroundCa2+-activated K+ channels have been implicated in cancer cell growth, metastasis, and tumor angiogenesis. Here we hypothesized that high mRNA and protein expression of the intermediate-conductance Ca2+-activated K+ channel, KCa3.1, is a molecular marker of clear cell Renal Cell Carcinoma (ccRCC) and metastatic potential and survival.Methodology/principal findingsWe analyzed channel expression by qRT-PCR, immunohistochemistry, and patch-clamp in ccRCC and benign oncocytoma specimens, in primary ccRCC and oncocytoma cell lines, as well as in two ccRCC cell lines (Caki-1 and Caki-2). CcRCC specimens contained 12-fold higher mRNA levels of KCa3.1 than oncocytoma specimens. The large-conductance channel, KCa1.1, was 3-fold more highly expressed in ccRCC than in oncocytoma. KCa3.1 mRNA expression in ccRCC was 2-fold higher than in the healthy cortex of the same kidney. Disease specific survival trended towards reduction in the subgroup of high-KCa3.1-expressing tumors (p<0.08 vs. low-KCa3.1-expressing tumors). Progression-free survival (time to metastasis/recurrence) was reduced significantly in the subgroup of high-KCa3.1-expressing tumors (p<0.02, vs. low-KCa3.1-expressing tumors). Immunohistochemistry revealed high protein expression of KCa3.1 in tumor vessels of ccRCC and oncocytoma and in a subset of ccRCC cells. Oncocytoma cells were devoid of KCa3.1 protein. In a primary ccRCC cell line and Caki-1/2-ccRCC cells, we found KCa3.1-protein as well as TRAM-34-sensitive KCa3.1-currents in a subset of cells. Furthermore, Caki-1/2-ccRCC cells displayed functional Paxilline-sensitive KCa1.1 currents. Neither KCa3.1 nor KCa1.1 were found in a primary oncocytoma cell line. Yet KCa-blockers, like TRAM-34 (KCa3.1) and Paxilline (KCa1.1), had no appreciable effects on Caki-1 proliferation in-vitro.Conclusions/significanceOur study demonstrated expression of KCa3.1 in ccRCC but not in benign oncocytoma. Moreover, high KCa3.1-mRNA expression levels were indicative of low disease specific survival of ccRCC patients, short progression-free survival, and a high metastatic potential. Therefore, KCa3.1 is of prognostic value in ccRCC.

Project description:BackgroundRunt-related transcription factor 1 (RUNX1) was previously reported to play a dual role in promoting or suppressing tumorigenesis in various malignancies. A public dataset from The Cancer Genome Atlas (TCGA) was used to evaluate the role of RUNX1 in clear cell renal cell carcinoma (ccRCC).MethodsThe Wilcoxon signed-rank test was used to compare the expression of RUNX1 in ccRCC tissues and normal tissues. The Wilcoxon signed-rank test and logistic regression were utilized to investigate the relationship between clinicopathological factors and RUNX1 expression. Additionally, we analysed the differences in prognosis between patients with high and low expression of RUNX1 via the Kaplan-Meier method and Cox regression. Gene set enrichment analysis (GSEA) was performed to explore the mechanisms of RUNX1 in ccRCC.ResultsThe expression of RUNX1 in ccRCC tissues was significantly higher than that in normal tissues. High expression of RUNX1 was significantly associated with gender (p = 0.003), clinical stage (p < 0.001), tissue infiltration (p < 0.001), lymph node metastasis (p = 0.037) and histological grade (p < 0.001). Logistic regression analysis showed that high RUNX1 expression was significantly correlated with gender (OR = 1.71 for male vs. female, p = 0.004), histological grade (OR = 11.61 for grade IV vs. I, p < 0.001), clinical stage (OR = 1.55 for stage III/IV vs. I/II, p = 0.014) and tissue infiltration (OR = 1.54 for positive vs. negative, p = 0.018). Kaplan-Meier survival curves revealed that the prognosis of patients with ccRCC with high RUNX1 expression was worse than that of patients with ccRCC with low RUNX1 expression (p < 0.001). Univariate Cox regression analysis showed that high RUNX1 expression was strongly correlated with poor prognosis (HR = 1.60, 95% CI [1.31-1.97], p < 0.001). In addition, high expression of RUNX1 was an independent prognostic factor for poor overall survival (OS), with an HR of 1.50 (95% CI [1.20-1.87], p < 0.001) in multivariate Cox analysis. GSEA showed that the apoptosis, B cell receptor signalling pathway, calcium signalling pathway, chemokine signalling pathway, JAK/STAT signalling pathway, MAPK signalling pathway, p53 signalling pathway, pathways in cancer, T cell receptor signalling pathway, Toll-like receptor signalling pathway, VEGF signalling pathway, and Wnt signalling pathway were significantly enriched in the RUNX1 high-expression phenotype. In conclusion, RUNX1 can be used as a novel prognostic factor and therapeutic target in ccRCC.

Project description:BackgroundPrevious reports have shown that short/branched chain acyl-CoA dehydrogenase (ACADSB) plays an important role in glioma, but its role in clear cell renal carcinoma (ccRCC) has not been reported.MethodsThe TIMER and UALCAN databases were used for pan-cancer analysis. RNA sequencing and microarray data of patients with ccRCC were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus database. The differential expression of ACADSB in ccRCC and normal kidney tissues was tested. Correlations between ACADSB expression and clinicopathological parameters were assessed using the Wilcoxon test. The influences of ACADSB expression and clinicopathological parameters on overall survival were assessed using Cox proportional hazards models. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different ACADSB expression phenotypes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on genes with similar expression patterns to ACADSB. Correlations between ACADSB and ferroptosis-related genes were assessed using Spearman's correlation analysis.ResultsPan-cancer analysis revealed that ACADSB is down-regulated in multiple cancers, and decreased expression of ACADSB correlates with poor prognosis in certain types of cancer. Differential expression analyses revealed that ACADSB was down-regulated in ccRCC, indicating that ACADSB expression could be a single significant parameter to discriminate between normal and tumor tissues. Clinical association analysis indicated that decreased ACADSB expression was associated with high tumor stage and grade. The Cox regression model indicated that low ACADSB expression was an independent risk factor for the overall survival of patients with ccRCC. GSEA showed that 10 gene sets, including fatty acid (FA) metabolism, were differentially enriched in the ACADSB high expression phenotype. GO and KEGG pathway enrichment analysis revealed that ACADSB-related genes were significantly enriched in categories related to FA metabolism, branched-chain amino acid (BCAA) metabolism, and iron regulation. Spearman's correlation analysis suggested that the expression of ACADSB was positively correlated with the expression of ferroptosis driver genes.ConclusionsACADSB showed good diagnostic and prognostic abilities for ccRCC. The downregulation of ACADSB might promote tumorigenesis and tumor progression by inhibiting FA catabolism, BCAA catabolism, and ferroptosis in ccRCC.

Project description:Stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, have been gradually recognized as a potential therapeutic target for various malignancies, particularly in clear-cell renal cell carcinoma (ccRCC). However, the prognostic value of SCD1 in ccRCC is still unknown. The aim of this study is to evaluate the clinical significance of SCD1 expression in patients with ccRCC. SCD1 expression in tumor tissues obtained from 359 patients who underwent nephrectomy for ccRCC are retrospectively assessed. During a median follow-up of 63 months (range: 1-144month), 56 patients in total died before the last follow-up in this study. Survival curves were plotted with the Kaplan-Meier method and compared with the log-rank test. Meanwhile, univariate and multivariate Cox regression models were applied to evaluate the prognostic value of SCD1 expression in overall survival (OS) for ccRCC patients. Moreover, SCD1 was enrolled into a newly built nomogram with factors selected by multivariate analysis, and the calibration was built to evaluate the predictive accuracy of nomogram. High SCD1 expression occurred in 61.6% (221/359) of ccRCC patients, which was significantly associated with age (p = 0.030), TNM stage (p = 0.021), pN stage (p = 0.014), Fuhrman grade (p = 0.014) and tumor sizes (p = 0.040). In multivariate analysis, SCD1 expression was confirmed as an adverse independent prognostic factor for OS. The prognostic accuracy of TNM stage, Fuhrman grade and tumor sizes was significantly increased when SCD1 expression was added. The independent prognostic factors, pT stage, pN stage, Fuhrman grade and tumor sizes, as well as SCD1 expression were integrated to establish a predictive nomogram with high predictive accuracy. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high SCD1 expression is an independent prognostic factor for OS in patients with ccRCC. Our data suggest that the expression of SCD1 might guide the clinical decisions for patients with ccRCC.

Dataset Information

High expression of Aldolase A predicts poor survival in patients with clear-cell renal cell carcinoma.

Publications

High expression of Aldolase A predicts poor survival in patients with clear-cell renal cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets