The majority of clear cell renal cell carcinomas (ccRCCs) are caused by an accumulation of hypoxia-inducible factor (HIF) and the overexpression of downstream genes in response to the von Hippel-Lindau (VHL) gene becoming inactivated. In the present study, our hypothesis was that BNIP3, a gene positioned downstream of HIF, would be expressed at a higher level in ccRCC; however, instead, lower levels of BNIP3 expression were identified in RCC tumor tissues compared with adjacent non-tumor tissues. These changes were associated with lower levels of VHL, and higher levels of HIF and vascular endothelial growth factor. BNIP3 was also undetectable in three investigated RCC cell lines (786-O, ACHN, A498) and GRC-1-1 cells. Methylation of the BNIP3 promoter was not detected, and neither did treatment with a methylation inhibitor cause cell proliferation. However, treatment with a histone deacetylation inhibitor, trichostatin A (TSA), inhibited cultured RCC cell proliferation, promoted apoptosis and restored BNIP3 expression. Furthermore, histone deacetylation of the BNIP3 promoter was identified in ACHN and 786-O cells, and the acetylation status was restored following TSA treatment. Taken together, the results of the present study suggest that histone deacetylation, but not methylation, is most likely to cause BNIP3 inactivation in RCC. The data also indicated that restoration of BNIP3 expression by a histone deacetylation inhibitor led to growth inhibition and apoptotic promotion in RCC.
Background
A novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes and platelet counts, is associated with the prognosis of several cancers. The present study evaluates the prognostic significance of SII in non-metastatic renal cell carcinoma (RCC).
Method
The present study retrospectively reviewed the medical record of patients with non-metastatic RCC who underwent nephrectomy between 2010 and 2013. Receiver operating characteristic (ROC) curve analysis was performed to identify the optimal cut-off value. In addition, the propensity score matching (PSM) was performed with a matching ratio of 1:1. Univariate and multivariate Cox proportional hazards models were used to identify the prognostic factors. The results were reported by hazard ratio (HR) with 95% confidence interval (95% CI).
Results
A total of 646 patients were included in the final analysis. High SII group (> 529) was significantly associated with older age (P = 0.014), larger tumor (P < 0.001), higher pathological T stage (P < 0.001), higher tumor grade (P < 0.001) and more tumor necrosis (P < 0.001). Multivariate Cox regression analysis demonstrated that the higher preoperative SII was significantly associated with worse overall survival (OS) (HR = 2.26; 95% CI 1.44–3.54; P < 0.001) and cancer-specific survival (CSS) (HR = 2.17; 95% CI 1.33–3.55; P = 0.002). After PSM, elevated preoperative SII was an independent predictor of poor OS (HR = 1.78; 95% CI 1.1–2.87; P = 0.018) and CSS (HR = 1.8; 95% CI 1.07–3.03; P = 0.027).
Conclusion
In conclusion, preoperative SII is associated with adverse factors for RCC. Furthermore, higher preoperative SII is an independent predictor of poor OS and CSS in surgically treated patients with non-metastatic RCC. More prospective and large scale studies are warranted to validate our findings.
Objective
The modified Glasgow prognostic score (mGPS), a combination of C-reactive protein (CRP) and albumin levels, reflects systemic inflammation and nutritional status. This score has been shown to have prognosis value for various tumors. In the present study, we evaluated the prognostic value of mGPS for patients with renal cell carcinoma (RCC).
Methods
Literature search was conducted based on PubMed, Embase, and Cochrane Central Register of Controlled Trials up to December 2018. We pooled HRs and 95% CIs to evaluate the correlation between mGPS and survival in patients with RCC.
Results
Twelve studies comprising 2,391 patients were included in the present study for quantitative synthesis. Our studies demonstrated that higher mGPS was significantly correlated to poor overall survival (HR=4.31; 95%CI, 2.78–6.68;
P
<0.001), cancer-specific survival (HR=5.88; 95%CI, 3.93–8.78;
P
<0.001), recurrence-free survival (HR=3.15; 95%CI, 2.07–4.79;
P
<0.001), and progression-free survival (HR=1.91; 95%CI, 1.27–2.89;
P
=0.002). Subgroup analyses also confirmed the overall results.
Conclusion
mGPS could serve as a predictive tool for the survival of patients with RCC. In the different subgroups, the results are also consistent with previous results. In conclusion, pretreatment higher mGPS is associated with poorer survival in patients with RCC. Further external validations are necessary to strengthen this concept.
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