Tumor necrosis as a prognostic variable for the clinical outcome in patients with renal cell carcinoma: a systematic review and meta-analysis

Abstract

BackgroundTumor necrosis (TN) correlates with adverse outcomes in numerous solid tumors. However, its prognostic value in renal cell carcinoma (RCC) remains unclear. In this study, we performed a meta-analysis to evaluate associations between TN and cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS) and progression-free-survival (PFS) in RCC.MethodsElectronic searches in PubMed, EMBASE and Web of Science were conducted according to the PRISMA statement. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate relationships between TN and RCC. A fixed- or random-effects model was used to calculate pooled HRs and 95%CIs according to heterogeneity.ResultsA total of 34 cohort studies met the eligibility criteria of this meta-analysis. The results showed that TN was significantly predictive of poorer CSS (HR = 1.37, 95% CI: 1.23–1.53, p < 0.001), OS (HR = 1.29, 95% CI: 1.20–1.40, p < 0.001), RFS (HR = 1.55, 95% CI: 1.39–1.72, p < 0.001) and PFS (HR = 1.31, 95% CI: 1.17–1.46, p < 0.001) in patients with RCC. All the findings were robust when stratified by geographical region, pathological type, staging system, number of patients, and median follow-up.ConclusionsThe present study suggests that TN is associated with CSS, OS, RFS and PFS clinical outcomes of RCC patients and may serve as a predictor of poor prognosis in these patients.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4773-z) contains supplementary material, which is available to authorized users.

Selection of metastasis competent subclones in the tumour interior: TRACERx renal

“…2c). Necrosis, a feature associated with tumour aggressiveness 13 , harsh hypoxic environmental conditions 13 and poor prognosis 14 , was additionally found (as expected) to be signi cantly higher in the tumour centre (p=0.006, Fig. 2d).…”

“…Given these additional competencies, it is thus unsurprising that subclones from the tumour centre are better adapted to seed secondary metastatic sites. Necrotic primary tumour subclones have been shown to have greater propensity to seed metastases in pre-clinical models 17 , and clinically a recent systematic meta-analysis across 34 studies demonstrated tumour necrosis to be associated with reduced cancerspeci c survival in RCC 14 . Biologically, tumour necrosis is classically associated with chronic hypoxia caused by rapid tumour growth and inadequate blood supply 18 .…”

Extracellular K+Dampens T Cell Functions: Implications for Immune Suppression in the Tumor Microenvironment

“…Tumor necrosis has been associated with poor prognosis in a variety of cancer types. [7][8][9] Dying/necrotic tumor cells release intracellular contents/ factors in the TME and thus alter the extracellular milieu. One of the key factors that have recently been identified is an accumulation of increased amount of extracellular potassium ([K + ] e ) in the fluid around tumors (8-15-fold higher than that present in normal serum).…”

Influence of gene expression on survival of clear cell renal cell carcinoma

“…We and others reported candidate biomarkers, such as long non-coding RNAs, 9 gene expression signatures, [10][11][12][13][14][15] epigenetics 16 for ccRCC progression and/or survival. [17][18][19] However, there is currently no clinically accepted molecular biomarker for ccRCC progression.…”