Chromosomal deletion of 9p21 is linked to poor patient prognosis in papillary and clear cell kidney cancer

Abstract Background BCL2L13 belongs to the BCL2 super family, with its protein product exhibits capacity of apoptosis-mediating in diversified cell lines. Previous studies have shown that BCL2L13 has functional consequence in several tumor types, including ALL and GBM, however, its function in kidney cancer remains as yet unclearly. Methods Multiple web-based portals were employed to analyze the effect of BCL2L13 in kidney cancer using the data from TCGA database. Functional enrichment analysis and hubs of BCL2L13 co-expressed genes in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were carried out on Cytoscape. Evaluation of BCL2L13 protein level was accomplished through immunohistochemistry on paraffin embedded renal cancer tissue sections. Western blotting and flow cytometry were implemented to further analyze the pro-apoptotic function of BCL2L13 in ccRCC cell line 786-0. Results BCL2L13 expression is significantly decreased in ccRCC and pRCC patients, however, mutations and copy number alterations are rarely observed. The poor prognosis of ccRCC that derived from down-regulated BCL2L13 is independent of patients’ gender or tumor grade. Furthermore, BCL2L13 only weakly correlates with the genes that mutated in kidney cancer or the genes that associated with inherited kidney cancer predisposing syndrome, while actively correlates with SLC25A4. As a downstream effector of BCL2L13 in its pro-apoptotic pathway, SLC25A4 is found as one of the hub genes that involved in the physiological function of BCL2L13 in kidney cancer tissues. Conclusions Down-regulation of BCL2L13 renders poor prognosis in ccRCC and pRCC. This disadvantageous factor is independent of any well-known kidney cancer related genes, so BCL2L13 can be used as an effective indicator for prognostic evaluation of renal cell carcinoma.

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Frequency of heterozygous carriage of mutations in the genes of Notch signal path in patients with clear cell kidney cancer and in the populations of the Volga-Ural region

Yakut Medical Journal ◽

10.25789/ymj.2021.73.01 ◽

2021 ◽

pp. 5-7

Author(s):

I.R. Gilyazova ◽

E.A. Ivanova ◽

A.A. Izmailov ◽

I.R. Sultanov ◽

R.I. Safiullin ◽

...

Keyword(s):

Kidney Cancer ◽

Clear Cell ◽

Ural Region ◽

Notch Signal ◽

Signal Path ◽

Volga Ural Region

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Low Levels of TRIM28-Interacting KRAB-ZNF Genes Associate with Cancer Stemness and Predict Poor Prognosis of Kidney Renal Clear Cell Carcinoma Patients

Cancers ◽

10.3390/cancers13194835 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4835

Author(s):

Patrycja Czerwinska ◽

Andrzej Adam Mackiewicz

Keyword(s):

Gene Expression ◽

Kidney Cancer ◽

Cancer Progression ◽

Clear Cell ◽

Cell Cancer ◽

The Cancer Genome Atlas ◽

Specific Gene ◽

Stem Cell Markers ◽

Kidney Tumors ◽

Cancer Stemness

Krüppel-associated box zinc finger (KRAB-ZNF) proteins are known to regulate diverse biological processes, such as embryonic development, tissue-specific gene expression, and cancer progression. However, their involvement in the regulation of cancer stemness-like phenotype acquisition and maintenance is scarcely explored across solid tumor types, and to date, there are no data for kidney renal clear cell cancer (KIRC). We have harnessed The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database transcriptomic data and used several bioinformatic tools (i.e., GEPIA2, GSCALite, TISIDB, GSEA, CIBERSORT) to verify the relation between the expression and genomic alterations in KRAB-ZNFs and kidney cancer, focusing primarily on tumor dedifferentiation status and antitumor immune response. Our results demonstrate a significant negative correlation between KRAB-ZNFs and kidney cancer dedifferentiation status followed by an attenuated immune-suppressive response. The transcriptomic profiles of high KRAB-ZNF-expressing kidney tumors are significantly enriched with stem cell markers and show a depletion of several inflammatory pathways known for favoring cancer stemness. Moreover, we show for the first time the prognostic role for several KRAB-ZNFs in kidney cancer. Our results provide new insight into the role of selected KRAB-ZNF proteins in kidney cancer development. We believe that our findings may help better understand the molecular basis of KIRC.

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Decreased DC‑SIGNR expression in hepatocellular carcinoma predicts poor patient prognosis

Oncology Letters ◽

10.3892/ol.2019.11074 ◽

2019 ◽

Cited By ~ 1

Author(s):

Hai‑Bing Xia ◽

Hui‑Ju Wang ◽

Shu‑Shu Song ◽

Jun‑Gang Zhang ◽

Xiang‑Lei He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Patient ◽

Patient Prognosis

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PPM1D Is a Therapeutic Target in Childhood Neural Tumors

Cancers ◽

10.3390/cancers13236042 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6042

Author(s):

Jelena Milosevic ◽

Diana Treis ◽

Susanne Fransson ◽

Gabriel Gallo-Oller ◽

Baldur Sveinbjörnsson ◽

...

Keyword(s):

Cell Cycle Control ◽

Neuroblastoma Cells ◽

Negative Regulator ◽

Activating Mutations ◽

Poor Patient ◽

Chromosome 17Q ◽

Childhood Medulloblastoma ◽

Aggressive Tumors ◽

Patient Prognosis ◽

Mdm2 Inhibitor

Childhood medulloblastoma and high-risk neuroblastoma frequently present with segmental gain of chromosome 17q corresponding to aggressive tumors and poor patient prognosis. Located within the 17q-gained chromosomal segments is PPM1D at chromosome 17q23.2. PPM1D encodes a serine/threonine phosphatase, WIP1, that is a negative regulator of p53 activity as well as key proteins involved in cell cycle control, DNA repair and apoptosis. Here, we show that the level of PPM1D expression correlates with chromosome 17q gain in medulloblastoma and neuroblastoma cells, and both medulloblastoma and neuroblastoma cells are highly dependent on PPM1D expression for survival. Comparison of different inhibitors of WIP1 showed that SL-176 was the most potent compound inhibiting medulloblastoma and neuroblastoma growth and had similar or more potent effects on cell survival than the MDM2 inhibitor Nutlin-3 or the p53 activator RITA. SL-176 monotherapy significantly suppressed the growth of established medulloblastoma and neuroblastoma xenografts in nude mice. These results suggest that the development of clinically applicable compounds inhibiting the activity of WIP1 is of importance since PPM1D activating mutations, genetic gain or amplifications and/or overexpression of WIP1 are frequently detected in several different cancers.

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