IRF5 is associated with adverse postoperative prognosis of patients with non-metastatic clear cell renal cell carcinoma.
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ABSTRACT:
SUBMITTER: Bai Q
PROVIDER: S-EPMC5546472 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P?<?0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients' survival together with other clinical parameters (P?<?0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients' RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P?<?0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments.
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Project description:A total of 3 metastatic and 3 non-metastatic ccRCC tissues were collected from patients. These tissues were flash frozen in liquid nitrogen immediately after surgery and subsequently stored at -80℃. All the resected nodules or metastatic masses were identified as renal tumor by pathologic examination. No patients received anticancer treatments before surgery in this study. We analyzed gene expression microarray data from our gene chip with 3 metastatic ccRCC tissues compared with 3 non-metastatic ccRCC tissues.
2017-08-17 | GSE88948 | GEO
Project description:BACKGROUND:Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress. METHOD:Diagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters. RESULTS:The ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p?<?0.001), TNM stage (p?<?0.001), morphological grade (p?<?0.001), and patients outcome (5?year cancer specific survival (pCSS5yr) p?<?0.001 and cumulative incidence of progress (pCIP5yr) p?<?0.001. An integrated genomic and epigenomic analysis in the ccRCCs, revealed significant correlations between the total number of genetic aberrations and total number of hypermethylated CpGs (R?=?0.435, p?<?0.001), and predicted mitotic age (R?=?0.407, p?<?0.001). We identified a promoter methylation classifier (PMC) panel consisting of 172 differently methylated CpGs accompanying progress of disease. Classifying non-metastatic patients using the PMC panel showed that PMC high tumors had a worse prognosis compared with the PMC low tumors (pCIP5yr 38% vs. 8%, p?=?0.001), which was confirmed in non-metastatic ccRCCs in the publically available TCGA-KIRC dataset (pCIP5yr 39% vs. 16%, p?<?0.001). CONCLUSION:DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.
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