Membranous location of EGFR immunostaining is associated with good prognosis in renal cell carcinoma.
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ABSTRACT:
SUBMITTER: Kallio JP
PROVIDER: S-EPMC2394310 | biostudies-other | 2003 Oct
REPOSITORIES: biostudies-other
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Project description:Frizzled class receptor 1 (FZD1), a receptor for Wnt signaling pathway. Overexpression of FZD1 has been detected in many cancer tissues and cells resulting in tumor development and drug resistance. However, its expression status and prognostic merit in renal cancer still remains unclear. We screened the FZD1 mRNA in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) from TCGA database and Oncomine database. We then detected FZD1 mRNA expression in sunitinib-resistant cells and the corresponding parental cells by qRT-PCR. FZD1 level was significantly upregulated in renal cancer tissues, renal cancer cell lines and their corresponding sunitinib-resistant cells. FZD1 level was also associated with the clinicopathological characteristics of ccRCC patients that could discriminate metastasis, pathological stage, recurrence and prognosis in ccRCC patients. The Kaplan-Meier survival curve and the log-rank test revealed FZD1 was higher in lower clinical stage and grade that correlated with better overall survival (OS) and disease-free survival (DFS) in total and subgroups of ccRCC patients. Both univariate and multivariate cox regression analysis indicated that high FZD1 level was an independent predictor of good prognosis for OS (HR 0.569, P=0.001) and DFS (HR 0.559, P=0.036) in ccRCC patients. Using cBioportal program, less than 1% mutation in the patients with renal cancer was observed, the alterations in FZD1 were correlated with better OS (P=0.0404) in ccRCC patients. Finally, the result of KEGG pathway analysis predicted seven potential pathways that FZD1 and its related genes got involved in ccRCC, including Hippo signaling pathway. This indicated potential therapeutic targets of ccRCC. In conclusion, our results suggested that expression status of FZD1 had a diagnostic value and prognostic value in ccRCC patients, it also may serve as a potential drug target to relieve sunitinib resistance in renal cancer patients.
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Project description:Background:Renal cell carcinoma (RCC) is one of the most common tumors in urinary tract tumors. However, the mechanism that supports renal cell carcinoma is unclear. The function of transcription elongation factor A (SII)-like 2 (TCEAL2) and its association with human cancer have not been reported. Materials and Methods:To explore the role of TCEAL2 in carcinogenesis of clear cell renal cell carcinoma (ccRCC), we performed bioinformatics analysis to determine the expression levels of TCEAL2 in ccRCC specimens and normal kidney tissue and then verified findings with our samples by qPCR, Western blot and immunohistochemistry staining. Furthermore, the lentiviral vectors were used to increase the expression of TCEAL2 in ccRCC cell lines. The immunofluorescence assay was taken to observe the subcellular location of TCEAL2 in ccRCC cells, and CCK-8 and flow cytometry were introduced for assessing cell proliferation and cell cycle of ccRCC cells, respectively. Results:Compared with adjacent normal kidney tissue and human proximal tubular epithelial cells, the expression of TCEAL2 in ccRCC tissues and cell lines was down-regulated. Patients who had low expression of TCEAL2 had a statistically significant late tumor stage. Restore of TCEAL2 in ccRCC cells inhibited cell proliferation and induced cell cycle arrest in S phase of ccRCC cells. Conclusion:To our knowledge, this is the first report of TCEAL2 expression changes in ccRCC. We found that the decrease of TCEAL2 expression may be related to the occurrence of ccRCC. Further research is needed to clarify the molecular mechanism of TCEAL2 in progress of ccRCC.
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Project description:Clear cell renal cell carcinoma (ccRCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ?4 cm. miR-194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR-194 as a prognostic marker in ccRCC. In a cohort of 234 patients with primary ccRCC, we correlated miR-194 expression level with multiple clinicopathological features including disease-free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR-194 expression from normal kidney to primary ccRCC (P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR-194 expression has significantly longer disease-free survival (P = 0.041) and overall survival (P = 0.031) compared to those with lower expression. In multivariate analysis, miR-194-positive tumors retain significance in disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in ccRCC. Moreover, miR-194 is a marker for good prognosis for patients with small renal masses (P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR-194 expression between RCC subtypes. ccRCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR-194 is predicted to target key molecules and pathways involved in RCC progression. miR-194 represents a prognostic biomarker in ccRCC.
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Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is a tumor that frequently shows the hematogenous pathway and tends to be resistant to radiotherapy and chemotherapy. However, the exact mechanism of ccRCC metastasis remains unknown.MethodsDifferentially expressed genes (DEGs) of three gene expression profiles (GSE85258, GSE105288 and GSE22541) downloaded from the Gene Expression Omnibus (GEO) database were analyzed by GEO2R analysis, and co-expressed DEGs among the datasets were identified using a Venn drawing tool. The co-expressed DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and hub genes were determined based on the protein-protein interaction network established by STRING. After survival analysis performed on UALCAN website, possible key genes were selected and verified in ccRCC cell lines and ccRCC tissues (n = 44). Statistical analysis was conducted using GraphPad Prism (Version 8.1.1).ResultsA total of 104 co-expressed DEGs were identified in the three datasets. Pathway analysis revealed that these genes were enriched in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption and focal adhesion. Survival analysis on 17 hub genes revealed that four key genes with a significant impact on survival: procollagen C-endopeptidase enhancer (PCOLCE), prolyl 4-hydroxylase subunit beta (P4HB), collagen type VI alpha 2 (COL6A2) and collagen type VI alpha 3 (COL6A3). Patients with higher expression of these key genes had worse survival than those with lower expression. In vitro experiments revealed that the mRNA expression levels of PCOLCE, P4HB and COL6A2 were three times higher and that of COL6A3 mRNA was 16 times higher in the metastatic ccRCC cell line Caki-1 than the corresponding primary cell line Caki-2. Immunohistochemistry revealed higher expression of the proteins encoded by these four genes in metastatic ccRCC compared with tumors from the corresponding primary sites, with statistical significance.ConclusionPCOLCE, P4HB, COL6A2 and COL6A3 are upregulated in metastatic ccRCC and might be related to poor prognosis and distant metastases.
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Project description:IRF5 is one member of IRFs family, and is critical for host immunity and cell response. In the present study, we sought to search the clinical and prognostic value of IFR5 in patients with non-metastatic ccRCC.IRF5 proved to be an adverse independent prognostic factor for overall survival (p < 0.001) and recurrence free survival (p = 0.002). The newly built nomograms could give better prediction for overall survival and recurrence free survival in ccRCC patients.We included 264 individuals who were diagnosed with non-metastatic clear cell renal cell carcinoma in the present study. Immunohistochemistry staining was performed on tissue microarrays to evaluate the IRF5 expression. χ2 test, Fisher's exact test, t test, Kaplan-Meier method and Cox proportional hazard model were applied to evaluate the prognostic value of IRF5. Two nomograms were constructed to predict clinical outcomes for ccRCC patients after surgery.IRF5 was an adverse independent prognostic factor for both overall survival and recurrence free survival in patients with non-metastatic ccRCC.
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Project description:Renal cell carcinoma (RCC) is a common type of kidney cancer. Normally, surgical treatment can prolong life, but only for patients with early stage tumors. However, it is difficult for early detection strategies to distinguish between benign and malignant kidney tumors. Therefore, potential biomarkers for early diagnosis and prognosis of RCC are needed. Intriguingly, mounting evidence has demonstrated that many long noncoding RNAs (lncRNAs) are strongly linked to cancers. Indeed, promising RCC-associated lncRNA biomarkers have also been identified. However, the functional and prognostic roles of the antisense (AS) serum deprivation response (SDPR) lncRNA (SDPR-AS) in RCC remain largely unknown. The aims of this study were to investigate the expression and prognostic relevance of SDPR-AS in RCC. We uncovered the downregulated expressions of both lncRNA SDPR-AS and its protein-coding gene, SDPR, in RCC tissues compared to the matched normal tissues. Furthermore, SDPR-AS and SDPR expressions were positively correlated. Overexpression and knockdown experiments suggested that SDPR-AS and SDPR were coregulated in RCC cell lines. In addition, overexpression of SDPR-AS suppressed cell migration and invasion, but not cell growth. Furthermore, expression of SDPR-AS was associated with tumor differentiation and lymphatic metastasis. Kaplan-Meier survival and log-rank tests demonstrated the association of elevated expression of SDPR-AS with increased overall survival. In conclusion, our results suggest that the SDPR-AS may serve as a prognostic biomarker and therapeutic target of RCC.
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Project description:One-third of clear cell renal cell carcinoma (ccRCC) patients present with metastasis at the time of diagnosis. The prognosis of these patients is poor. To identify potential prognostic biomarkers and therapeutic targets for ccRCC, we re-evaluated published long non-coding RNA (lncRNA) expression profiling data from the Gene Expression Omnibus and ArrayExpress database. We found that five lncRNAs were differentially expressed in ccRCC and adjacent tissues. These lncRNAs were assessed in an independent cohort of 71 paired patient samples using real-time PCR. Differences in expression of three of the lncRNAs (ENSG00000177133, TCL6, and ENSG00000244020) were validated in this analysis. Kaplan-Meier analysis indicated that low expression of ENSG00000177133 and TCL6 was associated with a poor prognosis. Univariate and multivariate regression analyses demonstrated that TCL6 but not ENSG00000177133 expression was an independent predictor of ccRCC aggressiveness and had hazard ratios predictive of clinical outcome. TCL6 expression was negatively correlated with pTNM stage. Overexpression of TCL6 in 786-O and Caki-1 ccRCC cells decreased proliferation and increased apoptosis compared to controls. Our results indicate that lncRNA expression is altered in ccRCC and that decreased TCL6 expression may be an independent adverse prognostic factor in ccRCC patients.
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Project description:MUC3A is a membrane-associated mucin that recent evidence reveals the role of MUC3A in pathogenesis and progression of cancers. To evaluate the association between MUC3A expression with overall survival (OS) and recurrence-free survival (RFS) in patients with localized clear-cell renal cell carcinoma (ccRCC), we retrospectively detected MUC3A expression in samples of 384 postoperative localized ccRCC patients by immunohistochemistry. Median follow-up was 73 months (range: 42 - 74 mo). Overall, 41 patients died, 47 experienced recurrence. High MUC3A expression occurred in 45.8% of localized ccRCC cases, which was significantly associated with high pT-stage, high Fuhrman grade, high frequency of necrosis and LVI, and increased risk of recurrence and death (Logrank test P < 0.001 and P < 0.001, respectively). By multivariate analysis, MUC3A expression was confirmed as an adverse independent prognostic factor for OS and RFS. The prognostic accuracy of UISS, SSIGN, Leibovich models was significantly increased when MUC3A expression was integrated. Meanwhile, MUC3A was enrolled into a newly built nomogram with other factors selected by multivariate analysis. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high MUC3A expression is an adverse prognostic biomarker for OS and RFS in postoperative localized ccRCC patients.
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