Genetic and Chromosomal Aberrations and Their Clinical Significance in Renal Neoplasms

Yap, Ning Yi; Rajandram, Retnagowri; Ng, Keng Lim; Pailoor, Jayalakshmi; Fadzli, Ahmad Nazran; Gobé, Glenda C.

doi:10.1155/2015/476508

Cited by 26 publications

(24 citation statements)

References 257 publications

(299 reference statements)

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“…Elevated mRNA expression was the most alteration. Tumorigenesis and the progression of RCC are complex and multi-faceted, and genetic alteration plays an important role in this process (35). We found a low to high correlation among the differentially expressed CXC chemokines, suggesting that these cytokines play a synergistic role in the tumorigenesis and progression of RCC.…”

Section: Discussionmentioning

confidence: 66%

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment

Zeng¹,

Sun

Li³

et al. 2020

Front. Oncol.

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Background: Renal cell carcinoma (RCC) is one of the most common malignances with an ever-increasing incidence and high mortality. Cross-talk between cancer cells and interstitial cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. CXC chemokines in the tumor microenvironment can modulate immune cell trafficking and regulate tumor cell activities, thus exerting anti-tumor immunological effects and affecting patient outcomes; however, the expression and prognostic values of CXC chemokines in RCC have not been clarified. Methods: ONCOMINE, GEPIA, UALCAN, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TRRUST, LinkedOmics, and TIMER were utilized in this study. Results: The transcriptional levels of CXCL1/2/5/6/9/10/11/16 in RCC tissues were significantly elevated while the transcriptional levels of CXCL3/7/12/13 were significantly reduced. A significant correlation was found between the expression of CXC1/5/9/10/11/13 and the pathological stage of RCC patients. RCC patients with low transcriptional levels of CXCL1/2/3/5/13 were associated with a significantly better prognosis. The functions of differentially expressed CXC chemokines are primarily related to the chemokine signaling pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the SRC family of tyrosine kinases (LCK, LYN, and FYN), mitogen-activated protein kinases (MAPK1 and MAPK3), and CSNK1D are CXC chemokine targets. We found significant correlations among the expression of CXC chemokines and the infiltration of six types of immune cells (B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells). Conclusions: Our results may provide novel insights for the selection of immunotherapeutic targets and prognostic biomarkers for renal cell carcinoma.

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Section: Discussionmentioning

confidence: 66%

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment

Zeng¹,

Sun

Li³

et al. 2020

Front. Oncol.

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“…The loss of one copy of chromosomes 1, 2, 6, 10, 13, 17, 21 and Y occurs in the majority of chRCC cases. Since losses of chromosomes 1 and Y have been reported in benign oncocytoma [5,16,18,19], we speculated that only loss of chromosomes 2, 6, 10, 13, 17 and 21 may be associated with outcome in chRCC patients. The frequencies of loss of these chromosomes were similar in both the TCGA-KICH and the Swiss cohort.…”

Section: Chromosomal Loss and Patient Outcomementioning

confidence: 99%

“…Chromophobe renal cell carcinoma (chRCC) is the third most common histological subtype of RCC and accounts for approximately 5-7% of RCC [1][2][3]. Although chRCC patients have better prognoses than patients with clear cell RCC (ccRCC) or papillary RCC (pRCC) [1][2][3][4][5], about 5-7% of patients die of metastatic disease [4,6,7]. Therefore, it is of utmost importance to identify prognostic factors, which can better predict the small patient group with clinical progression after surgical resection.…”

Section: Introductionmentioning

confidence: 99%

Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients

Ohashi

Angori

Batavia

et al. 2020

Cancers

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Chromophobe renal cell carcinoma (chRCC) patients have good prognosis. Only 5%–10% patients die of metastatic disease after tumorectomy, but tumor progression cannot be predicted by histopathological parameters alone. chRCC are characterized by losses of many chromosomes, whereas gene mutations are rare. In this study, we aim at identifying genes indicating chRCC progression. A bioinformatic approach was used to correlate chromosomal loss and mRNA expression from 15287 genes from The Cancer Genome Atlas (TCGA) database. All genes in TCGA chromophobe renal cancer dataset (KICH) for which a significant correlation between chromosomal loss and mRNA expression was shown, were identified and their associations with outcome was assessed. Genome-wide DNA copy-number alterations were analyzed by Affymetrix OncoScan® CNV FFPE Microarrays in a second cohort of Swiss chRCC. In both cohorts, tumors with loss of chromosomes 2, 6, 10, 13, 17 and 21 had signs of tumor progression. There were 4654 genes located on these chromosomes, and 13 of these genes had reduced mRNA levels, which was associated with poor outcome in chRCC. Decreased CDKN1A expression at mRNA (p = 0.02) and protein levels (p = 0.02) were associated with short overall survival and were independent predictors of prognosis (p < 0.01 and <0.05 respectively). CDKN1A expression status is a prognostic biomarker independent of tumor stage. CDKN1A immunohistochemistry may be used to identify chRCC patients at greater risk of disease progression.

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“…This suggests that genetic factors may have a critical influence on the aetiology of RCC. Several studies have confirmed the role of genetic factors in the development of RCC [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 95%

Association between vascular endothelial growth factor gene polymorphisms and the risk and prognosis of renal cell carcinoma: A systematic review and meta-analysis

Tang

Qin

et al. 2017

Oncotarget

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The aim of the meta-analysis was to clarify the associations between vascular endothelial growth factor (VEGF) polymorphisms and the risk and prognosis of renal cell carcinoma (RCC). A meta-analysis was performed by searching the databases PubMed, EMBASE and Web of Science for the relevant available studies until August 1st, 2016, and fourteen studies met the inclusion criteria. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of such associations. Besides, the pooled hazard ratios (HRs) with 95% CIs were used to evaluate the overall survival (OS). Fixed- or random-effects models were conducted according to existence of heterogeneity. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. Overall, this meta-analysis included a total of 8,275 patients, who had been accrued between November 2002 and September 2015. Meta-analysis indicated that -2578C/A, +936C/T and +405G/C polymorphisms in the VEGF gene correlated with elevated RCC risk, especially in Asian populations. Moreover, VEGF -1154G/A and -634C/G polymorphisms were found significantly associated with poor OS of RCC. Therefore, this meta-analysis revealed that VEGF -2578C/A, +936C/T, +405G/C polymorphisms were associated with an elevated susceptibility to RCC, indicating that these three polymorphisms might be risk factors for RCC, especially in Asian populations.

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Genetic and Chromosomal Aberrations and Their Clinical Significance in Renal Neoplasms

Cited by 26 publications

References 257 publications

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment

Identification of Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in the Renal Cell Carcinoma Microenvironment

Loss of CDKN1A mRNA and Protein Expression Are Independent Predictors of Poor Outcome in Chromophobe Renal Cell Carcinoma Patients

Association between vascular endothelial growth factor gene polymorphisms and the risk and prognosis of renal cell carcinoma: A systematic review and meta-analysis

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