Targeting the Deterministic Evolutionary Trajectories of Clear Cell Renal Cell Carcinoma

Kowalewski, Adam; Zdrenka, Marek; Grzanka, Dariusz; Szylberg, Łukasz

doi:10.3390/cancers12113300

Cited by 6 publications

(4 citation statements)

References 76 publications

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“…Then, targeting KIF11 would be an attractive complement to evolution-targeted therapy. Evolution-targeted therapy in ccRCC is a novel con-cept that relies on patient stratification according to the deterministic evolutionary trajectory of the tumour [23]. Currently there are 7 well described evolutionary trajectories in ccRCC according to the tumour's genomic characteristics, evolution mode, and clinical course [24].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of kif11 is a poor prognostic factor in clear cell renal cell carcinoma

Kowalewski¹,

Jaworski²,

Antosik³

et al. 2022

pjp

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Introduction: Unresectable renal cell carcinoma continues to be a great challenge due to our limited understanding of its underlying pathophysiology. We explored the relationship between KIF11 protein expression and the clinical courses of clear cell renal cell carcinoma (ccRCC) using a tissue microarray. Material and methods: The tissue microarray contained specimens derived from 90 patients, cancer and matched adjacent non-cancerous tissue (2 cores per case), followed up for 7 years. Tumour samples were evaluated for KIF11 expression using the H-score, and their correlations with clinicopathological data and survival data were analysed. Results: 72.7% of ccRCC tissues presented KIF11 cytoplasmic expression with a median value of 20 (interquartile range 0-200). The nuclear staining was positive in 36.36% of ccRCC tissues. Among controls, nuclear KIF11 expression was absent, but cytoplasmic expression was identified in all cases, with a median value of 230 (interquartile range 45-290). Cytoplasmic KIF11 expression in ccRCC tissues was lower than in the control tissues and was positively correlated with tumour grade and mortality (p < 0.05). KIF11 nuclear expression did not correlate with overall survival. Conclusions: Elevated expression of KIF11 predicts poor clinical outcome in ccRCC patients. Downregulation of KIF11 may provide a new therapeutic strategy for ccRCC.

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Section: Discussionmentioning

confidence: 99%

Overexpression of kif11 is a poor prognostic factor in clear cell renal cell carcinoma

Kowalewski¹,

Jaworski²,

Antosik³

et al. 2022

pjp

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“…At present, molecularly targeted drug resistance is a huge challenge in achieving a better prognosis for advanced RCC [41]. Several studies have suggested that drug resistance results from the involvement of multiple factors such as tumor stem cells and the activation of other pathways [42]. PDGF is an angiogenic factor that can induce tumor angiogenesis and directly or indirectly promote the proliferation and migration of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Identifying the Potential Role and Prognostic Value of the Platelet-Derived Growth Factor Pathway in Kidney Renal Clear Cell Carcinoma

Xin

Sun

Jin

et al. 2022

Journal of Oncology

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The platelet-derived growth factor (PDGF) pathway is important in angiogenesis, which can accelerate the formation of vessels in tumor tissues and promote the progression of malignant tumors. To clarify the role of PDGF in the occurrence of renal cell carcinoma and targeted drug resistance, we explored the pathway in kidney renal clear cell carcinoma (KIRC) through bioinformatics analysis with the aim of supporting comprehensive and individualized therapy. First, we found 40 genes related to the PDGF pathway through gene set enrichment analysis and then obtained their expressions and clinical data in 32 different cancers from The Cancer Genome Atlas (TCGA). Mutations in these genes (including copy number and single-nucleotide variation) and mRNA expression were also detected. Next, we conducted a hazard ratio analysis to determine whether the PDGF pathway genes were risk or protective factors in tumors. Although PDGF-related genes acted as traditional oncogenes and were closely related to tumor angiogenesis in many cancers, our results indicated that most genes had a protective role in KIRC. We further analyzed the methylation modification of PDGF pathway genes and found that they were prevalent in 32 different cancers. Furthermore, 539 KIRC samples obtained from TCGA were divided into three clusters based on the mRNA expression of PDGF genes, including normal, inactive, and active PDGF gene expressions. The results from survival curve analysis indicated that the active PDGF cluster of patients had the best survival rate. Using the three clusters, we studied the correlation between the PDGF pathway and 12 common targeted drugs, as well as classical oncogenes and infiltrating immune cells. A prognostic risk model was constructed based on the PDGF score using LASSO-Cox regression analysis to analyze the value of the model in predicting the prognosis of patients with KIRC. Finally, 11 genes were selected for LASSO regression analysis, and the results demonstrated the high predictive value of this risk model and its close relationship with the pathological characteristics of KIRC (metastasis, size, grade, stage, etc.). In addition, we found that the risk score was an independent risk factor correlated with overall survival through univariate and multivariate analyses and a nomogram was built to assess patient prognosis. In conclusion, the occurrence and development of KIRC may be associated with an abnormally activated PDGF pathway, which may be a potential drug target in the treatment of KIRC.

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“…Among these, clear cell renal cell cancer (ccRCC) is the commonest, accounting for the majority of cancer-related deaths [ 2 ]. Since the early loss of function is uncommon in patients suffering from renal cell carcinoma, about one-third of patients have metastatic disease at diagnosis [ 3 ]. In addition, those with localized tumors have up to 40% risk of recurrence following complete resection [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

ORP5 promotes tumor metastasis via stabilizing c-Met in renal cell carcinoma

Zhang

Zhou

et al. 2022

Cell Death Discov.

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ORP5, a lipid transporter, has been reported to increase the metastasis of several cancers. However, the potential mechanisms of ORP5 in renal cell carcinoma (RCC) remain unclear. In this study, we demonstrated that ORP5 was commonly overexpressed in tumor cells and tissues of RCC, and associated with tumor progression. Overexpression of ORP5 could promote RCC cells migration and invasion. In addition, the results suggested that the expression of ORP5 was favorably associated with c-Met expression, and ORP5 promoted RCC cells metastasis by upregulating c-Met in vitro and in vivo. Mechanistically, ORP5 facilitated the ubiquitination and degradation of c-Cbl (the E3 ligase of c-Met), and thus inhibited c-Met lysosomal degradation, which resulted in the stabilization of c-Met. In general, these findings revealed the role of ORP5 in contributing to tumorigenesis via upregulating c-Met in RCC.

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Targeting the Deterministic Evolutionary Trajectories of Clear Cell Renal Cell Carcinoma

Cited by 6 publications

References 76 publications

Overexpression of kif11 is a poor prognostic factor in clear cell renal cell carcinoma

Overexpression of kif11 is a poor prognostic factor in clear cell renal cell carcinoma

Identifying the Potential Role and Prognostic Value of the Platelet-Derived Growth Factor Pathway in Kidney Renal Clear Cell Carcinoma

ORP5 promotes tumor metastasis via stabilizing c-Met in renal cell carcinoma

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