Decreased prolyl hydroxylase 3 mRNA expression in oncocytomas compared with clear cell renal cell carcinoma

2020 ◽  
Vol 35 (4) ◽  
pp. 80-86
Author(s):  
Spyridon Kampantais ◽  
Ilias Kounatidis ◽  
Vasiliki Kotoula ◽  
Ioannis Vakalopoulos ◽  
Konstantinos Gkagkalidis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Prolyl Hydroxylase ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Fresh Frozen

Introduction: Hypoxia inducible factors (HIF) and prolyl hydroxylase domain (PHD) enzymes play a central role in tumor progression in clear cell renal cell carcinoma (ccRCC). However, there are currently no data regarding the behavior of this pathway (HIF/PHD) in a large number of benign renal tumors, the oncocytomas. The aim of the present study was to compare the expression levels of these factors between ccRCC and oncocytoma tumors. Material and methods: A total of 56 fresh frozen specimens from patients with ccRCC and 14 oncocytoma specimens were analyzed via reverse transcription-quantitative polymerase chain reaction in order to assess the expression levels of HIF-1α, HIF-2α, PHD1, PHD2, and PHD3. The analysis involved both fresh frozen tumor samples as well as adjacent normal kidney tissues. Results: In ccRCC, HIF-1α and HIF-2α levels were upregulated in 65.5% and 71.4% of cases, respectively. PHD3 was downregulated only in 15.4% of the ccRCC cases, in contrast with oncocytoma cases, which exhibited low expression levels in the majority. The upregulation of PHD3 messenger RNA (mRNA) levels in ccRCC when compared with oncocytoma was statistically significant ( P<0.001). No other comparisons (HIF-1α, HIF-2α, PHD1, and PHD2) were significantly different. HIF-2α and PHD3 mRNA expression levels were negatively correlated with Fuhrman Grade ( P=0.029 and P=0.026, respectively) in ccRCC. Conclusion: To the best of our knowledge, this is the first time that the HIF/PHD pathway was compared between ccRCC and a common benign tumor, identifying the upregulation of PHD3 as the possible underlying factor guiding the difference in the behavior of ccRCC.

scholarly journals Expression and clinical significance of PTPN12 in clear cell renal cell carcinoma

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052093604
Author(s):  
Yi Jin ◽  
Tian-xi Wang ◽  
Hao Li ◽  
Peng Guo ◽  
Qing-qing Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Relative Expression ◽  
Normal Tissues ◽  
Mrna Expression Levels

Background Clear cell renal cell carcinoma (ccRCC) is a common urological disease. Expression of the protein tyrosine phosphatase 12 gene ( PTPN12) is decreased in many cancers; however, the relationship between PTPN12 gene function and renal cancer remains unclear. Methods We detected PTPN12 protein expression in ccRCC and corresponding normal tissues from 64 patients with ccRCC by immunohistochemistry, and relative PTPN12 mRNA levels by real-time quantitative polymerase chain reaction. The relationships between the relative expression levels of PTPN12 mRNA and the patients’ clinical data were analyzed. Results PTPN12 protein and mRNA expression levels were significantly lower in ccRCC compared with the corresponding normal tissues. The mRNA expression levels in the ccRCC and corresponding normal tissues from the 64 patients with ccRCC were 0.459±0.445 and 1.001±0.128, respectively, compared with the control (glyceraldehyde 3-phosphate dehydrogenase). There was a significant correlation between relative expression of PTPN12 mRNA in ccRCC tissues and tumor diameter and clinical stage. Conclusion The expression levels of PTPN12 protein and mRNA were significantly lower in ccRCC tissues compared with normal tissues. The role of PTPN12 may provide new insights and evidence to aid the diagnosis and targeted therapy of ccRCC.

scholarly journals Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Daniel Vergho ◽  
Susanne Kneitz ◽  
Andreas Rosenwald ◽  
Charlotte Scherer ◽  
Martin Spahn ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Expression Levels

scholarly journals COL6A2/3 can serve as potential therapeutic targets and prognostic biomarkers for clear cell renal cell carcinoma

2020 ◽  
Author(s):  
Wingkeung Yiu ◽  
Can-Xuan Li ◽  
Jie Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Therapeutic Targets ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Cell Renal Cell Carcinoma ◽  
Tumorigenesis And Progression

Abstract Background: Growing evidence has shown that the type VI collagen alpha chain (COL6A) family involved in the tumorigenesis and progression of diverse malignancies; however, its biological roles and potential mechanisms in clear cell renal cell carcinoma (ccRCC) remain unknown. The study was designed to explore the potential mechanisms and functions of COL6As in ccRCC.Methods: ONCOMINE and GEPIA databases were used to compare the transcriptional expression data of COL6As in ccRCC samples and normal renal samples. UALCAN database was utilized to determine the association between clinicopathological features and COL6As expression. Kaplan–Meier method was employed to determine the prognostic value of COL6As mRNA expression in ccRCC. CBioPortal database was used to investigate the genetic alterations of COL6As in ccRCC. Co-expression analyses, functional enrichment analyses, and gene set enrichment analysis (GSEA) were utilized to explore the potential action mechanisms of COL6As in ccRCC. Finally, we estimated the relationship between COL6As expression with immune cell infiltrates.Results: Upregulated transcriptional COL6A2/COL6A3 expression was observed in ccRCC specimens by comparison with noncancerous renal specimens. Patients with increased COL6A2/COL6A3 mRNA expression have a poor clinical outcome and unfavorable prognosis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analyses showed that COL6A2/COL6A3 might promote the tumorigenesis and progression of ccRCC by involving in several cancer-related pathways, such as axon guidance, focal adhesion, ECM receptor interaction. Besides, we found that COL6A2/COL6A3 expression was significantly associated with immune infiltration levels in ccRCC.Conclusions: COL6A2 and COL6A3 could act as candidate prognostic biomarkers and therapeutic targets in ccRCC. However, further experimental work was required to validate the conclusions.

scholarly journals Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in the Era of Targeted Therapies and Personalized Medicine

2013 ◽  
Vol 137 (4) ◽  
pp. 467-480 ◽  
Author(s):  
Rajen Goyal ◽  
Elizabeth Gersbach ◽  
Ximing J. Yang ◽  
Stephen M. Rohan
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumor ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Immunohistochemical Stains

Context.—The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and—with the exception of some rare tumors—the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies. Objective.—To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management. Data Sources.—Published literature and personal experience. Conclusions.—In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.

scholarly journals Differentiation of Clear Cell Renal Cell Carcinoma from other Renal Cell Carcinoma Subtypes and Benign Oncocytoma Using Quantitative MDCT Enhancement Parameters

Medicina ◽  
2020 ◽  
Vol 56 (11) ◽  
pp. 569
Author(s):  
Claudia-Gabriela Moldovanu ◽  
Bianca Petresc ◽  
Andrei Lebovici ◽  
Attila Tamas-Szora ◽  
Mihai Suciu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumors ◽  
3D Analysis ◽  
Imaging Features ◽  
Enhancement Ratio ◽  
Cell Renal Cell Carcinoma ◽  
Renal Masses

Background and objectives: The use of non-invasive techniques to predict the histological type of renal masses can avoid a renal mass biopsy, thus being of great clinical interest. The aim of our study was to assess if quantitative multiphasic multidetector computed tomography (MDCT) enhancement patterns of renal masses (malignant and benign) may be useful to enable lesion differentiation by their enhancement characteristics. Materials and Methods: A total of 154 renal tumors were retrospectively analyzed with a four-phase MDCT protocol. We studied attenuation values using the values within the most avidly enhancing portion of the tumor (2D analysis) and within the whole tumor volume (3D analysis). A region of interest (ROI) was also placed in the adjacent uninvolved renal cortex to calculate the relative tumor enhancement ratio. Results: Significant differences were noted in enhancement and de-enhancement (diminution of attenuation measurements between the postcontrast phases) values by histology. The highest areas under the receiver operating characteristic curves (AUCs) of 0.976 (95% CI: 0.924–0.995) and 0.827 (95% CI: 0.752–0.887), respectively, were demonstrated between clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC)/oncocytoma. The 3D analysis allowed the differentiation of ccRCC from chromophobe RCC (chrRCC) with a AUC of 0.643 (95% CI: 0.555–0.724). Wash-out values proved useful only for discrimination between ccRCC and oncocytoma (43.34 vs 64.10, p < 0.001). However, the relative tumor enhancement ratio (corticomedullary (CM) and nephrographic phases) proved useful for discrimination between ccRCC, pRCC, and chrRCC, with the values from the CM phase having higher AUCs of 0.973 (95% CI: 0.929–0.993) and 0.799 (95% CI: 0.721–0.864), respectively. Conclusions: Our observations point out that imaging features may contribute to providing prognostic information helpful in the management strategy of renal masses.

scholarly journals Unilateral synchronous papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma: a case report with KRAS and PIK3CA mutations

2020 ◽  
Author(s):  
Hyun Jung Lee ◽  
Dong Hoon Shin ◽  
Joon Young Park ◽  
So Young Kim ◽  
Chung Su Hwang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Mutation ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumors ◽  
Renal Neoplasm ◽  
Reverse Polarity ◽  
Cell Renal Cell Carcinoma ◽  
Exon 2

Abstract Background: The presence of histologically different neoplasms in the same organ is rare in pathologic practice. We report the first case of synchronous clear cell renal cell carcinoma (clear cell RCC) and papillary renal neoplasm with reverse polarity (PRNRP) with comprehensive immunohistochemical and molecular characterization using next-generation sequencing (NGS). Case presentation: A 61-year-old man was incidentally found to have a left renal mass on imaging studies performed for workup of left back pain and urine color change for one week. A laparoscopic left radical nephrectomy was performed. Gross examination showed lobulated masses measuring 5.6 × 4.0 × 3.3 cm in the upper to mid pole and 1.1 × 1.0 × 1.0 cm in the lower pole. Microscopic findings revealed these to be two different separate masses of clear cell renal cell carcinoma and papillary renal neoplasm with reverse polarity. NGS analyses revealed KRAS gene mutation (c.35G>T/p.G12V in exon 2) in the papillary renal neoplasm with reverse polarity, with PIK3CA gene mutation restricted to the clear cell renal cell carcinoma (c.1624G>A/p.E542K in exon 10).Conclusions: We report here an extraordinarily rare case of synchronous renal tumors of papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma. We identified simultaneous KRAS and PIK3CA mutations in two different renal masses in the same kidney for the first time. New pathologic assessment with comparative molecular analysis of mutational profiles may be helpful for tumor studies.

scholarly journals Expression levels of immune control points genes in renal cell carcinoma

2020 ◽  
pp. 64-65
Author(s):  
Н.В. Апанович ◽  
А.А. Алимов ◽  
П.В. Апанович ◽  
А.Ю. Кузеванова ◽  
Д.Ж. Мансорунов ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
New Drugs ◽  
Control Points ◽  
Immune Control ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Further Development

Внедрение в терапию рака новых препаратов на основе ингибирования иммунных контрольных точек (ИКТ) существенно улучшило прогноз для больных. Тем не менее, такая терапия не всегда эффективна. Для вскрытия возможных причин этого мы изучили уровни экспрессии PD-L1 и других генов ИКТ - IDO1, CEACAM1, PVR, TDO2, CD276, GAL9 и ADAM17 в образцах светлоклеточного почечно-клеточного рака. В результате анализа выявили наиболее часто экспрессирующиеся совместно с PD-L1 гены - IDO1, TDO2, CD276, GAL9 и ADAM17. Значимую корреляцию с экспрессией PD-L1 имела экспрессия генов ADAM17, PVR и CD276. Полученные данные могут иметь значение для дальнейшего развития терапии на основе блокирования ИКТ, включая PD-L1. The introduction of new drugs based on the inhibition of immune control points (ICР) into cancer therapy has significantly improved the prognosis for patients. However, such therapy is not always effective. To reveal the possible reasons for this, we studied the expression levels of PD-L1 and other ICР genes - IDO1, CEACAM1, PVR, TDO2, CD276, GAL9 and ADAM17 in samples of clear cell renal cell carcinoma. The analysis revealed the genes most often expressed together with PD-L1 - IDO1, TDO2, CD276, GAL9 and ADAM17. Significant correlation with the expression of PD-L1 was found for the expression of ADAM17, PVR, and CD276 genes. The data obtained may be important for the further development of therapy based on blocking ICP, including PD-L1.

scholarly journals Identification of ACSL4 as a biomarker and contributor of ferroptosis in clear cell renal cell carcinoma

2020 ◽  
Author(s):  
na guo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Transfection ◽  
Prognostic Significance ◽  
Expression Level ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Protein Ubiquitination

Abstract Background ACSL4 has been reported to be related to tumor genesis and involved in the processes of ferroptosis. However, the expression levels and prognostic value of ACSL4 in clear cell renal cell carcinoma (ccRCC) remain unclear. Methods The Oncomine and TCGA databases were used to predict the expression of ACSL4 mRNA in ccRCC and its association with ccRCC prognosis. The expression levels of ACSL4 were determined in human RCC tissues by real-time PCR. Kaplan-Meier curves were used to analyze the diagnostic and prognostic significance of ACSL4 in ccRCC. A ferroptosis inducer (erastin) was used to investigate the effects of ACSL4 on ferroptosis in ccRCC cell lines. Results The expression level of ACSL4 was significantly down-regulated in ccRCC tissues (P < 0.001), which was consistent with the analysis of the Oncomine and TCGA database. Then, immunohistochemical results demonstrated that the ACSL4 was weak or not detected in ccRCC tissues than that in normal tissues. ACSL4 differential expression level was significantly related to gender, ccRCC subtypes, nodal invasion, tumor grade and cancer stages (all P < 0.001). Survival analysis revealed that overall survival was favorable in ccRCC patients with ACSL4 high expression (P = 0.014). Overexpression of ACSL4 by gene transfection restores ferroptosis sensitization in cancer cells, whereas suppression of ACSL4 expression by RNAi increases ferroptosis resistance. Mechanically, protein ubiquitination may be involved in ACSL4-mediated ferroptosis. Conclusions As a monitor and contributor of ferroptosis, ACSL4 was decreased in ccRCC and served as a useful diagnostic and prognostic biomarker, which will be a new potential therapeutic target for ccRCC.

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