Nuclear factor-kappa B subunits and their prognostic cancer-specific survival value in renal cell carcinoma patients

Ng, Keng Lim; Yap, Ning Yi; Rajandram, Retnagowri; Small, David M.; Pailoor, Jayalakshmi; Ong, Teng Aik; Razack, Azad Hassan Abdul; Wood, Simon; Morais, Christudas; Gobé, Glenda C.

doi:10.1016/j.pathol.2018.03.003

Cited by 10 publications

(11 citation statements)

References 15 publications

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“…The present study found an overexpression of p65 in FeNTA-induced renal tumors, in agreement with previous observations for NF-κB in rat kidney after long term of FeNTA-exposure (36,37) and similar to what happens in patients' clear cell subtype tumors (14)(15)(16)19), as well as in some RCC human cell lines (13). Moreover, NF-κB activity is principally regulated by its inhibitory protein, IκBα, and a Figure 6.…”

Section: Discussionsupporting

confidence: 93%

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Differential behavior of NF‑κB, IκBα and EGFR during the renal carcinogenic process in an experimental model in�vivo

et al. 2020

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Renal cell carcinoma (RCC) is the most common type of cancer of the adult kidney. It is generally asymptomatic even at advanced stages, so opportune diagnosis is rare, making it almost impossible to study this cancer at its early stages. RCC tumors induced by ferric nitrilotriacetate (FeNTA) in rats histologically correspond to the human clear cell RCC subtype (ccRCC) and the exposure to this carcinogen during either one or two months leads to different early stages of neoplastic development. High levels of nuclear factor kappa B (NF-κB) and epidermal growth factor receptor (EGFR) as well as low levels of NF-κB inhibitor alpha (IκBα) are frequent in human RCC, but their status in FeNTA-induced tumors and their evolution along renal carcinogenesis is unclear. On this basis, in the present study NF-κB, IκBα and EGFR behavior was analyzed at different stages of the experimental renal carcinogenesis model. Similar to patients with RCC, neoplastic tissue showed high levels of p65, one of the predominant subunits of NF-κB in ccRCC and of EGFR (protein and mRNA), as well as a decrease in the levels of NF-κB's main inhibitor, IκBα, resulting in a classic oncogenic combination. Conversely, different responses were observed at early stages of carcinogenesis. After one month of FeNTA-exposure, NF-κB activity and EGFR levels augmented; but unexpectedly, IκBα also did. While after two months, NF-κB activity diminished, but EGFR and IκBα levels remained elevated. In conclusion, FeNTA-induced tumors and RCC human neoplasms are analogues regarding to the classic NF-κB, IκBα and EGFR behavior, and distinctive non-conventional combination of changes is developed at each early stage studied. The results obtained suggest that the dysregulation of the analyzed molecules could be related to different signaling pathways and therefore, to particular effects depending on the phase of the carcinogenic process.

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Section: Discussionsupporting

confidence: 93%

“…The p65 subunit was studied in all the aforementioned reports apart from Meteoglu et al (12) who analyzed the p50 subunit. Furthermore, Ng et al (19) reported a decrease in the levels of p50, p52 and c-Rel, as well as the absence of RelB, but an increase in p65 expression in human RCC tumors.…”

Section: Introductionmentioning

confidence: 98%

Differential behavior of NF‑κB, IκBα and EGFR during the renal carcinogenic process in an experimental model in�vivo

et al. 2020

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“…Tescalcin could promote RCC cells growth and metastasis by activating NF-κB pathway [24]. Besides, high expressions of p65 were correlated significantly with worse cancer-specific survival in ccRCC patients [25]. Amanda et al also reported that knockdown of NF-κB1 could suppress the growth and invasion of RCC in vitro and in vivo [26].…”

Section: Discussionmentioning

confidence: 99%

“…But, the underlying mechanisms of CRHBP involved in the pathogenesis of ccRCC were still elusive. NF-κB pathway has been demonstrated to play an important role in RCC [24][25][26]. Tescalcin could promote RCC cells growth and metastasis by activating NF-κB pathway [24].…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis reveals CRHBP inhibits renal cell carcinoma progression by regulating inflammation and apoptosis

Yang

Xiao

et al. 2019

Cancer Gene Ther

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Patients with renal cell carcinoma (RCC) usually develop drug resistance and have poor prognosis owing to its insensitive property. However, the underlying mechanisms of RCC are still unclear. We implemented an integrative analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets. Three genes (CRHBP, RAB25 and PSAT1) were found to be potential biomarkers in ccRCC and validated by four independent cohorts. Then, ccRCC patients with a decreased expression of CRHBP in tumor tissues had significantly poor survival by TCGA ccRCC datasets and verified by clinical samples as well as RCC cell lines. Overexpression of CRHBP suppressed cell proliferation, migration, invasion as well as apoptosis in vitro and in vivo. Moreover, the results of western blot analysis showed the effects of CRHBP via upregulating NF-κB and p53-mediated mitochondria apoptotic pathway. Our results suggested that CRHBP may be an effective target to treat ccRCC patients.

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“…All the slides were scanned using Aperio Image Scanning by Leica Biosystem at 40x magnification. The immunopositivity score was reported manually and also as a ratio of positive pixels [ 23 ]. The cut-off points were determined by using the formula below:

…”

Section: Methodsmentioning

confidence: 99%

A Study on the Immunohistochemical Expressions of Leptin and Leptin Receptor in Clear Cell Renal Cell Carcinoma

Perumal

Mun

Yap

et al. 2020

BioMed Research International

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Background. The mechanisms that link obesity and cancer development are not well-defined. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms. These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. Tissue proteins can be easily detected with immunohistochemistry (IHC), a technique widely used both in diagnostic and research laboratories. The identification of altered levels of leptin and leptin receptor proteins in tumour tissues may lead to targeted treatment for cancer. Objective. The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p<0.05 was considered significant. Results. There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC. Conclusion. In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.

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Nuclear factor-kappa B subunits and their prognostic cancer-specific survival value in renal cell carcinoma patients

Cited by 10 publications

References 15 publications

Differential behavior of NF‑κB, IκBα and EGFR during the renal carcinogenic process in an experimental model in�vivo

Differential behavior of NF‑κB, IκBα and EGFR during the renal carcinogenic process in an experimental model in�vivo

Integrative analysis reveals CRHBP inhibits renal cell carcinoma progression by regulating inflammation and apoptosis

A Study on the Immunohistochemical Expressions of Leptin and Leptin Receptor in Clear Cell Renal Cell Carcinoma

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