The Expression of Thrombospondin-1 and p53 in Clear Cell Renal Cell Carcinoma: Its Relationship to Angiogenesis, Cell Proliferation and Cancer Specific Survival

Zubac, Damir; Bostad, Leif; Kihl, Björn; Seidal, Tomas; Wentzel‐Larsen, Tore; Haukaas, Svein A.

doi:10.1016/j.juro.2009.07.015

Cited by 37 publications

(31 citation statements)

References 41 publications

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“…The remaining articles were further excluded for several reasons, such as no data available (hazard ratio [HR] and 95% confidence interval [CI]), low-quality studies17, and duplicate publication. Finally, 20 articles published from 2000 to 2016 with 5,398 patients satisfied the criteria for meta-analysis1112131415161819202122232425262728293031. A flowchart of the study selection process is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, the role of Ki-67 in the prognosis of RCC remains inconsistent. Ki-67 was considered an unfavorable prognostic marker in RCC in many studies11121314, but some studies reported that Ki-67 expression is prognostically irrelevant in RCC patients1516. To obtain a more precise evaluation of the prognostic and clinicopathological value of Ki-67 expression in RCC, we performed a systematic review and meta-analysis to evaluate the prognostic value of Ki-67 quantitatively and explore the associations of Ki-67 with the clinicopathological features of RCC.…”

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confidence: 99%

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Prognostic and clinicopathological role of high Ki-67 expression in patients with renal cell carcinoma: a systematic review and meta-analysis

Xie

Chen

et al. 2017

Sci Rep

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Previous studies have elevated the prognostic value of Ki-67 in renal cell carcinoma (RCC), but the reports are controversial and inconsistent. We conducted a systematic review and meta-analysis to clarify the significance of Ki-67 in RCC prognosis. We systematically searched PubMed, Web of Science, and Embase to identify relevant studies until April 2016. Based on the inclusion and exclusion criteria, 20 studies, including 5,398 patients, were eligible for further analysis. Results showed that high Ki-67 expression in RCC was associated with poor OS (HR = 1.95, 95% CI: 1.44–2.64), CSS (HR = 1.67, 95% CI: 1.47–1.89), and DFS (HR = 2.56, 95% CI: 1.79–3.67). In addition, high Ki-67 expression was significantly associated with TNM stage (III/IV vs. I/II: RR = 2.03, 95% CI: 1.68–2.44), pathological T stage (T3/T4 vs. T1/T2: RR = 1.67, 95% CI: 1.35–2.06), metastasis (yes vs. no: RR = 2.15, 95% CI: 1.77–2.62), and Fuhrman grade (III/IV vs. I/II: RR = 1.77, 95% CI: 1.20–2.60). Our study suggested that Ki-67 was a prognostic marker in RCC. High Ki-67 expression was correlated with poor prognosis and advanced clinicopathological features, and it could serve as a biomarker for disease management.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Prognostic and clinicopathological role of high Ki-67 expression in patients with renal cell carcinoma: a systematic review and meta-analysis

Xie

Chen

et al. 2017

Sci Rep

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“…THBS1 is one of the most potent physiological antiangiogenic factors and its expression has been reported as an independent prognostic factor in ccRCC with retained expression being associated with increased survival [31]. It is therefore somewhat surprising to observe down-regulation of THBS1 mRNA on YAP knockdown in all cell lines analyzed.…”

Section: Discussionmentioning

confidence: 96%

Hippo Signaling Mediates Proliferation, Invasiveness, and Metastatic Potential of Clear Cell Renal Cell Carcinoma

Schütte

Bisht

Heukamp

et al. 2014

Translational Oncology

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Recent work has identified dysfunctional Hippo signaling to be involved in maintenance and progression of various human cancers, although data on clear cell renal cell carcinoma (ccRCC) have been limited. Here, we provide evidence implicating aberrant Hippo signaling in ccRCC proliferation, invasiveness, and metastatic potential. Nuclear overexpression of the Hippo target Yes-associated protein (YAP) was found in a subset of patients with ccRCC. Immunostaining was particularly prominent at the tumor margins and highlighted neoplastic cells invading the tumor-adjacent stroma. Short hairpin RNA-mediated knockdown of YAP significantly inhibited proliferation, migration, and anchorage-independent growth of ccRCC cells in soft agar and led to significantly reduced murine xenograft growth. Microarray analysis of YAP knockdown versus mock-transduced ccRCC cells revealed down-regulation of endothelin 1, endothelin 2, cysteine-rich, angiogenic inducer, 61 (CYR61), and c-Myc in ccRCC cells as well as up-regulation of the cell adhesion molecule cadherin 6. Signaling pathway impact analysis revealed activation of the p53 signaling and cell cycle pathways as well as inhibition of mitogen-activated protein kinase signaling on YAP down-regulation. Our data suggest CYR61 and c-Myc as well as signaling through the endothelin axis as bona fide downstream effectors of YAP and establish aberrant Hippo signaling as a potential therapeutic target in ccRCC.

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“…TSP-1 was frequently studied for invasion, metastasis, and prognosis of malignancies, including ovarian cancer (24), gastric cancer (25), breast carcinoma (26), lung cancer (27), renal cell carcinoma (28), and pancreatic cancer (29). These studies demonstrated that low or absent expression of TSP-1 is associated with advanced stage cancer.…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin-1 and VEGF in inflammatory bowel disease

Alkım

Sakiz

Alkım

et al. 2012

Libyan Journal of Medicine

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Background and aimAngiogenesis is an important process in the pathogenesis of chronic inflammation. We aimed to study the angiogeneic balance in inflammatory bowel disease (IBD) by evaluating the expression of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) on colonic epithelial cells, together with the expression of inducible nitric oxide synthase (iNOS).MethodsTwenty-one ulcerative colitis (UC), 14 Crohn's disease (CD), 11 colorectal cancer patients, and 11 healthy controls colonic biopsy samples were evaluated immunohistochemically.ResultsThe expressions of TSP-1, VEGF, and iNOS in UC and CD groups were higher than expression in healthy control group, all with statistical significance. However, in colorectal cancer group, VEGF and iNOS expressions were increased importantly, but TSP-1 expression was not statistically different from healthy control group's expression. Both TSP-1 and VEGF expressions were correlated with iNOS expression distinctly but did not correlate with each other.ConclusionsBoth pro-angiogeneic VEGF and antiangiogeneic TSP-1 expressions were found increased in our IBD groups, but in colorectal cancer group, only VEGF expression was increased. TSP-1 increases in IBD patients as a response to inflammatory condition, but this increase was not enough to suppress pathologic angiogenesis and inflammation in IBD.

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The Expression of Thrombospondin-1 and p53 in Clear Cell Renal Cell Carcinoma: Its Relationship to Angiogenesis, Cell Proliferation and Cancer Specific Survival

Cited by 37 publications

References 41 publications

Prognostic and clinicopathological role of high Ki-67 expression in patients with renal cell carcinoma: a systematic review and meta-analysis

Prognostic and clinicopathological role of high Ki-67 expression in patients with renal cell carcinoma: a systematic review and meta-analysis

Hippo Signaling Mediates Proliferation, Invasiveness, and Metastatic Potential of Clear Cell Renal Cell Carcinoma

Thrombospondin-1 and VEGF in inflammatory bowel disease

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