VENUSS rising for papillary renal cell carcinoma prognostication?
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ABSTRACT:
SUBMITTER: Buchler T
PROVIDER: S-EPMC7475457 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
VENUSS rising for papillary renal cell carcinoma prognostication?
Annals of translational medicine 20200801 16
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Project description:Renal papillary cell carcinoma
| PRJNA749556 | ENA
Project description:Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. Micro-RNAs (miRNAs) are small noncoding RNAs that play a crucial role in regulating gene expression and are involved in various biological processes, including cancer development. To better understand the biology of this tumor, we aimed to analyze the miRNA expression profile of a set of CCPRCC using microarray and quantitative reverse transcription-polymerase chain reaction. A total of 15 cases diagnosed as CCPRCC were used in this study. Among the most differentially expressed miRNA in CCPRCC, we found miR-210, miR-122, miR-34a, miR-21, miR-34b*, and miR-489 to be up-regulated, whereas miR-4284, miR-1202, miR-135a, miR-1973, and miR-204 were down-regulated compared with normal renal parenchyma. To identify consensus of differentially regulated miRNA between CCPRCC, CCRCC, and PRCC, we additionally determined differential miRNA expression using 2 publically available microarray data sets from the NCBI Gene Expression Omnibus database (GSE41282 and GSE3798). This comparison revealed that the miRNA expression profile of CCPRCC shows some overlapping characteristics between CCRCC and PRCC. Moreover, CCPRCC lacks dysregulation of important miRNAs typically associated with aggressive behavior. In summary, we describe the miRNA expression profile of a relatively infrequent type of renal cancer. Our results may help in understanding the molecular underpinning of this newly recognized entity.
| S-EPMC4332813 | biostudies-literature
Project description:We used RNA-SEQ technique to detect lncRNAs expression differences in 53 pairs of tumor and adjacent normal tissues of renal papillary cell carcinoma
2024-05-22 | GSE180777 | GEO
Project description: Not available
| S-EPMC7723602 | biostudies-literature
Project description:Purpose of the reviewPapillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype and represents 15-20% of all RCC. Classification of pRCC is changing because novel tumour entities have been discovered in the last years. In this review, we summarise recent studies relevant for the understanding of the molecular complexity and the broader differential diagnosis of pRCC.Recent findingsIt has been 25 years ago, that pRCC was morphologically subdivided into type 1 and type 2. Recently described tumour entities in the 2022 WHO classification challenged this concept and allow a new view on the molecular background in pRCC. Biphasic hyalinizing psammomatous RCC and papillary renal neoplasm with reversed polarity are emerging tumour entities derived from the new concept of molecularly defined RCC subtypes. Immune checkpoint inhibition and tyrosine kinase inhibitors have been introduced as the new backbone in the first-line treatment of advanced pRCCs. To identify novel targeted treatments for patients with pRCC it is crucial to investigate the specific molecular background of pRCC considering emerging pRCC subtypes.SummaryIn the future, a deeper understanding of the correlation between molecular aberrations and new pRCC subtypes may improve the classification of pRCC patients and could reveal potential predictive biomarkers for each subgroup.
| S-EPMC9394504 | biostudies-literature
Project description:BackgroundPapillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist.MethodsWe performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis.ResultsType 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH).ConclusionsType 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).
| S-EPMC4775252 | biostudies-literature
Project description:BackgroundBesides the conventional clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC) is the second most common renal malignancy. Papillary RCCs can further be subdivided into two distinct subtypes. Although a clinical relevance of pRCC subtyping has been shown, little is known about the molecular characteristics of both pRCC subtypes.MethodsWe performed microarray-based microRNA (miRNA) expression profiling of primary ccRCC and pRCC cases. A subset of miRNAs was identified and used to establish a classification model for ccRCC, pRCC types 1 and 2 and normal tissue. Furthermore, we performed gene set enrichment analysis with the predicted miRNA target genes.ResultsOnly five miRNAs (miR-145, -200c, -210, -502-3p and let-7c) were sufficient to identify the samples with high accuracy. In a collection of 111 tissue samples, 73.9% were classified correctly. An enrichment of miRNA target genes in the family of multidrug-resistance proteins was noted in all tumours. Several components of the Jak-STAT signalling pathway might be targets for miRNAs that define pRCC tumour subtypes.ConclusionMicroRNAs are able to accurately classify RCC samples. Deregulated miRNAs might contribute to the high chemotherapy resistance of RCC. Furthermore, our results indicate that pRCC type 2 tumours could be dependent on oncogenic MYC signalling.
| S-EPMC3738121 | biostudies-literature
Project description:BackgroundNectin-4 contributes to tumor proliferation, lymphangiogenesis and angiogenesis in malignant tumors and is an emerging target in tumor therapy. In renal cell carcinoma (RCC) VEGF-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. Enfortumab vedotin-ejf (EV) is an antibody drug conjugate that targets Nectin-4. The aim of our study was to investigate the expression of Nectin-4 in a large cohort of papillary RCC specimens.Patients and methodsSpecimens were derived from the PANZAR consortium (Erlangen, Heidelberg, Herne, Homburg, Mainz, Mannheim, Marburg, Muenster, LMU Munich, TU Munich, and Regensburg). Clinical data and tissue samples from n = 190 and n = 107 patients with type 1 and 2 pRCC, respectively, were available. Expression of Nectin-4 was determined by immunohistochemistry (IHC).ResultsIn total, Nectin-4 staining was moderately or strongly positive in of 92 (48.4%) of type 1 and 39 (36.4%) type 2 of pRCC cases. No associations between Nectin-4 expression and age at diagnosis, gender, grading, and TNM stage was found. 5 year overall survival rate was not statistically different in patients with Nectin-4 negative versus Nectin-4 positive tumors for the overall cohort and the pRCC type 2 subgroup, but higher in patient with Nectin-4 positive pRCC type 1 tumors compared to Nectin-4 negative tumors (81.3% vs. 67.8%, p = 0.042).ConclusionNectin-4 could not be confirmed as a prognostic marker in pRCC in general. Due to its high abundance on pRCC specimens Nectin-4 is an interesting target for therapeutical approaches e.g. with EV. Clinical trials are warranted to elucidate its role in the pRCC treatment landscape.
| S-EPMC9500133 | biostudies-literature
Project description:Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer in ccRCC patients and the hazard ratio of death was 0.71 for ccRCC patients. No differences in PFS or ORR were detected between type I and II PRCC in this limited dataset. The median OS for type I pRCC was 20.0 months while the median OS for type II was 12.6 months (P = 0.096). The IMDC prognostic model was able to stratify pRCC patients into favorable risk (OS = 34.1 months), intermediate risk (OS = 17.0 months), and poor-risk groups (OS = 6.0 months). pRCC patient outcomes were inferior to ccRCC, even after controlling for IMDC prognostic factors. The IMDC prognostic model was able to effectively stratify pRCC patients.
| S-EPMC5430092 | biostudies-literature
Project description:Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a distinct entity, which shows a biallelic inactivation of the FH gene that consequently leads to FH protein expression and function loss, respectively. This alteration leads to an accumulation of the oncometabolite fumarate in the citrate cycle and various disorders of the cell balance and DNA processing. FH-deficient RCC often shows a morphologically overlapping spectrum with papillary renal cell carcinoma (type 2), whereby a typical mixture of growth patterns including tubulo-cystic, cribriform, and/or solid differentiation can be observed. A characteristic but non-specific morphological feature is prominent eosinophilic, virus-inclusion body-like nucleoli with perinucleolar halos. Tumoral immunohistochemical loss of FH expression supports the diagnosis but may be preserved in rare cases. Most FH-deficient RCCs show very aggressive biological behavior and are often metastasized at the time of diagnosis. The initial description encompassed RCC in association with the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, which also includes cutaneous and uterine leiomyomas. However, current data also show an increasing proportion of sporadic cases, so that a distinction (hereditary vs. sporadic) seems appropriate. So far, few but promising data on effective systemic therapeutic options have been reported. In summary, precise diagnosis is of great importance due to the frequent aggressive biological behavior, potential need to deviate from the therapeutic standard, and the possible indicator of a hereditary disease.
| S-EPMC8536582 | biostudies-literature