High Expression of GSDMC Is Associated with Poor Survival in Kidney Clear Cell Cancer
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ABSTRACT:
SUBMITTER: Cui Y
PROVIDER: S-EPMC8589493 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAldolase 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.MethodsThe 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.ResultsIn 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.ConclusionOur results suggest that ALDOA expression is an independent prognostic factor for OS in patients with ccRCC.
| S-EPMC5338975 | biostudies-literature
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.
| S-EPMC4388734 | biostudies-literature
Project description:Background: Specific lifestyle factors including tobacco-exposure are vital etiologic factors for renal cell carcinoma (RCC), F2R Like Thrombin/Trypsin Receptor 3 (F2RL3) is associated with smoking but it is unknown whether its expression translate into poor survival of clear cell RCC (ccRCC). In the current study, the expression profiling and prognostic value of F2RL3 in Chinese patients with ccRCC were investigated. Methods: Using Quantitative PCR analysis and immunohistochemistry, the relative expression levels of F2RL3 in 367 paired ccRCC and adjacent normal tissues were calculated. Cox regression analysis was used to identify independent prognostic factors and Kaplan-Meier analysis and a log-rank test were employed to evaluate the prognostic value of F2RL3. Results: We observed that high expression of F2RL3 mRNA and protein were strongly correlated with shorten progression-free survival (PFS) of ccRCC with hazard ratios (HR; 95% confidence interval (CI)) of 2.060 (1.410-3.009) and 1.657 (1.193-2.300), respectively, as well as with poor overall survival (OS) with HRs (95%CI) of 2.826 (1.713-4.662) and 1.712 (1.140-2.569), respectively. After adjustment for confounding factors including smoking status, elevated HRs (95%CI) of 2.113 (1.445-3.089) and 1.692 (1.218-2.352) were presented for PFS, respectively, and 2.936 (1.777-4.851) and 1.811 (1.203-2.725) were present for OS, respectively. Meanwhile, increased F2RL3 mRNA and protein level were reported to significantly associate with smoking-exposure and well-known prognostic factors (higher TNM stage and ISUP grade). Conclusion: These findings suggested that F2RL3 mRNA and protein level in ccRCC is a robust predictor of poorly prognostic phenotype. Exploring the causal relevance of F2RL3 in ccRCC development further warrants in the future study.
| S-EPMC6160688 | biostudies-literature
Project description:A recent point of focus in breast cancer (BC) research has been the utilization of cell-free DNA (cfDNA) and its concentration (cfDConc) and integrity (cfDI) as potential biomarkers. Though the association of cfDConc and poor survival is already recognized, studies on the prognostic value of cfDI have had contradictory results. Here, we provide further evidence to support the use of cfDI as a potential biomarker. We selected 204 Eastern Finnish BC cases with non-metastatic disease and isolated cfDNA from the serum collected at the time of diagnosis before any treatment was given. The cfDConc and cfDI were measured with a fluorometer and electrophoresis and analyzed with 25 years of survival data. High cfDConc was not an independent prognostic factor in our analyses while high cfDI was found to be an independent prognostic factor for poor OS (p = 0.020, hazard ratio (HR) = 1.57, 95% confidence interval (CI) 1.07-2.29, Cox) and BCSS (p = 0.006, HR = 1.93, 95% CI 1.21-3.08)). Inclusion of cfDI in the multivariate logistic regression model improved the predictive performance. Our results show high cfDI is an independent prognostic factor for poor OS and BCSS and improves the predictive performance of logistic regression models, thus supporting its prognostic potential.
| S-EPMC8467852 | biostudies-literature
Project description:Galectin-7, has a controversial role in tumor progression, can either suppress tumor growth or induce chemoresistance depends on different tumor histology types. The aim was to appraise Galectin-7 expression on the overall survival (OS) of patients with non-metastatic clear cell renal cell carcinoma (ccRCC) following surgery.High galectin-7 expression was specifically correlated with necrosis (P = 0.015). Multivariate analysis confirmed galectin-7 as an independent prognosticator for OS (P = 0.005). High galectin-7 expression suggested poor OS (P < 0.001), particularly with UISS intermediate and high score groups. Notably, the predictive accuracy of the traditional prognostic scores was improved when combined with galectin-7 expression.We retrospectively enrolled 416 patients who underwent nephrectomy at a single institute between 2008 and 2009 and detected their intratumor galectin-7 expression by immunohistochemistry. Kaplan-Meier method was conducted to plot survival curves and multivariate cox regression analysis for potential independent prognostic factors on OS. A nomogram was constructed with concordance index (C-index) and Akaike's Information Criteria (AIC) to appraise prognostic accuracy of different models.High galectin-7 expression is an independent adverse predictor for survival. Evaluation of galectin-7 could help guide postsurgical management for non-metastatic ccRCC patients.
| S-EPMC5173110 | biostudies-literature
Project description:Herpes virus entry mediator (HVEM), also called tumor necrosis factor receptor superfamily 14 (TNFRSF14), is highly expressed in various tumor tissues and plays critical roles in tumor biology. However, the role of HVEM in clear cell renal cell carcinoma (ccRCC) is unknown. This study evaluated the clinical importance of HVEM in patients with ccRCC. HVEM expression was assessed in fresh and 140 archived paraffin-embedded ccRCC tissue samples by quantitative RT-PCR, western blot, and immunohistochemical staining. HVEM expression was higher in ccRCC than in paired peritumor tissue. Kaplan-Meier analysis showed that high level of HVEM expression was associated with poor overall survival (OS) and disease-free survival (DFS) in patients with ccRCC (both P < 0.001). Multivariate analysis indicated that HVEM overexpression was independently prognostic of survival in ccRCC patients. Two novel nomogram systems were constructed by integrating HVEM expression and other clinical parameters to predict OS (c-index 0.75) and DFS (c-index 0.74) in these patients, with both having better predictive accuracy than traditional TNM (c-index 0.65 for OS and 0.639 for DFS) and Fuhrman (c-index 0.612 for OS and 0.641 for DFS) systems. In addition, HVEM silencing led to an observable reduction in tumor cells growth in vitro and in vivo. Taken together, these findings indicate that high HVEM expression is a novel and independent adverse predictor of clinical outcomes in patients with ccRCC and that HVEM may be a potential therapeutic target.
| S-EPMC6556608 | biostudies-literature
Project description:BACKGROUND The present study explored the expression of coiled-coil domain-containing 34 (CCDC34) in cervical cancer (CC) and its prognostic value. MATERIAL AND METHODS GEPIA and Oncomine cancer databases were mined to predict the CCDC34 differential expression level between a CC group and a normal group. Immunohistochemistry was performed to examine the CCDC34 expression in 67 CC and corresponding adjacent tissues. CD31 and vascular endothelial growth factor (VEGF) were stained to reflect tumor angiogenesis in 67 CC tissues. Kaplan-Meier univariate and Cox multivariate survival analysis were done to evaluate the correlation between CCDC34 expression and prognosis of CC patients. RESULTS Both GEPIA and Oncomine cancer databases mining results revealed that CCDC34 was more highly expressed in the CC group than in the normal group (all P<0.05). Our immunochemical staining data showed that CCDC34 expression was dramatically higher in CC than in adjacent normal tissues (71.6 vs. 20.9%; P<0.001). High expression of CCDC34 was strongly associated with histological grade (P=0.022), lymph node metastasis (P=0.044), and FIGO stage (P=0.002). Furthermore, patients with CCDC34-positive expression had much more MVD than those with CCDC34-negative expression (P<0.001). Kaplan-Meier survival analysis showed that CCDC34-positive expression was associated with worse overall survival (OS) (P=0.004) and disease-free survival (DFS) (P=0.005). Additionally, Cox multivariate analysis revealed that CCDC34 was an independent unfavorable prognostic parameter of DFS and OS (P=0.040 and 0.039, respectively). CONCLUSIONS High expression of CCDC34 is an independent unfavorable prognostic parameter for OS and DFS of CC patients, which was strongly associated with tumor angiogenesis.
| S-EPMC6256838 | biostudies-literature
Project description:BackgroundKidney renal clear cell carcinoma (KIRC) is the most common subtype of kidney cancer. Inorganic pyrophosphatase (PPA2) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate; few studies have reported its significance in cancers. Therefore, we aimed to explore the prognostic value of PPA2 in KIRC.MethodsPPA2 expression was detected via immunohistochemistry in a tissue chip containing specimens from 150 patients with KIRC. We evaluated the correlation between PPA2 expression, clinicopathological characteristics, and survival. Data from online databases and another cohort (paraffin-embedded specimens from 10 patients with KIRC) were used for external validation.ResultsPPA2 expression was significantly lower in KIRC tissues than in normal renal tissues (p < 0.0001). Low expression of PPA2 was significantly associated with a high histologic grade and poor prognosis. The differential expression of PPA2 was validated at the gene and protein levels. Multivariate Cox regression analysis showed that PPA2 expression was an independent prognostic factor in patients with KIRC. Gene set enrichment analysis suggested that decreased expression of PPA2 might be related to the epithelial-mesenchymal transition in KIRC.ConclusionsOur study demonstrated that PPA2 is an important energy metabolism-associated biomarker correlated with a favorable prognosis in KIRC.
| S-EPMC8428262 | biostudies-literature
Project description:Matrix metallopeptidase 9 (MMP9) was found to be associated with tumor aggressiveness. In this study, we focused on the correlation between MMP9 expression and clear cell renal carcinoma (ccRCC). Through the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) database and immunohistochemical (IHC) staining, we observed that compared with adjacent normal renal tissues, in ccRCC tissues the mRNA and protein levels of MMP9 were enhanced, and the mRNA levels of GTP-binding protein smg p21B(RAP1B), B rapidly accelerated fibrosarcoma (RAF), methyl ethyl ketone2 (MEK2), extracellular regulated protein kinases1 (ERK1), ERK2, v-ets avian erythroblastosis virus E26 oncogene homolog1 (ETS1) and ETS2 also increased. The Kaplan-Meier survival analysis suggested that high MMP9 expression was an unfavorable prognostic biomarker for ccRCC patients. Our results indicated that the increased expression level of MMP9 in ccRCC may be due to the activation of the Mitogen-activated protein kinases (MAPK)/ERK signaling pathway, and MMP9 may be an attractive target for ccRCC therapy.
| S-EPMC6035719 | biostudies-literature
Project description:Sperm-associated antigen 5 (SPAG5), a spindle-binding protein, regulates the process of mitosis. The present study focused on the relationship between SPAG5 expression and the clinicopathological characteristics and prognosis of ovarian cancer. First, we used the Gene Expression Omnibus (GEO) database to analyze SPAG5 expression in ovarian cancer and its clinical relevance. Subsequently, qPCR test was used to detect SPAG5 mRNA expression in 20 cases of ovarian cancer. The expression of SPAG5 protein in a tissue microarray containing 102 cases of ovarian cancer was detected by immunohistochemistry. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for the 102 ovarian cancer patients. In the GEO datasets, SPAG5 mRNA expression was significantly higher in ovarian cancer tissues than that in normal ovarian tissues (P < 0.001). qPCR and immunohistochemistry showed that SPAG5 expression in ovarian cancer tissues was significantly higher than that in paracancerous tissues (P = 0.002, P < 0.001). The high expression of SPAG5 in ovarian cancer was correlated with histological type (P = 0.009), lymph node metastasis (P = 0.001), distant metastasis (P = 0.001), TNM stage (P = 0.001), and prognosis (P = 0.001). The Kaplan-Meier curve indicated that rates of disease-free survival (DFS) and overall survival (OS) were even lower in patients with high SPAG5 expression. Multivariate analysis showed that SPAG5 expression (P = 0.001) and TNM staging (P = 0.002) were independent prognostic factors for the DFS of ovarian cancer. These results suggest that high SPAG5 expression was correlated with multiple clinicopathological features of ovarian cancer and can be used as an evaluation indicator for a poor ovarian cancer prognosis.
| S-EPMC7007403 | biostudies-literature