Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA163247 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell carcinoma (MRCC) and to validate them in a cellular model. Selected microRNAs were studied in serum from MRCC patients and healthy individuals. Methods: We screened 673 microRNAs using TaqMan Low-density Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n=41). Differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenoytpes selected from an independent cohort (n=117). Results were validated in a cellular model of sunitinib resistance and studied in serum from healthy individuals and MRCC patients. Results: TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p=0.0074). High expression of miR-942, miR-133a, miR484, and miR-628-5p was significantly associated with decreased time-to-progression and overall survival. These microRNAs were overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive parental cell line. Serum levels of miR-942, miR-133a, miR-484, miR-146a-5p, miR-374a and miR-486-5p were significantly reduced in MRCC patients compared to healthy controls. Conclusions: Our strategy identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity and resistance to sunitinib. Mir-942 was the best predictor of efficacy. Results were confirmed in a cellular model of sunitinib resistance. We also identified exosome derived serum microRNAs differentially expressed in MRCC patients and healthy individuals. Taqman Low Density Array for 6 FFPE tissues obtained from extreme phenotype MRCC patients, (n=3 marked resistance to sunitinib treatment patients and n=3 marked sensitivity to sunitinib treatment patients), was performanced to screen 667 microRNAs.
2014-09-30 | E-GEOD-37766 | biostudies-arrayexpress
Project description:Purpose: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell carcinoma (MRCC) and to validate them in a cellular model. Selected microRNAs were studied in serum from MRCC patients and healthy individuals. Methods: We screened 673 microRNAs using TaqMan Low-density Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n=41). Differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenoytpes selected from an independent cohort (n=117). Results were validated in a cellular model of sunitinib resistance and studied in serum from healthy individuals and MRCC patients. Results: TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p=0.0074). High expression of miR-942, miR-133a, miR484, and miR-628-5p was significantly associated with decreased time-to-progression and overall survival. These microRNAs were overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive parental cell line. Serum levels of miR-942, miR-133a, miR-484, miR-146a-5p, miR-374a and miR-486-5p were significantly reduced in MRCC patients compared to healthy controls. Conclusions: Our strategy identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity and resistance to sunitinib. Mir-942 was the best predictor of efficacy. Results were confirmed in a cellular model of sunitinib resistance. We also identified exosome derived serum microRNAs differentially expressed in MRCC patients and healthy individuals.
2014-09-30 | GSE37766 | GEO
Project description:Background/Objective: MicroRNAs (miRNAs) play a pivotal role in cancerogenesis and cancer progression, but their specific role in metastasis of clear cell renal cell carcinomas (ccRCCs) as so-called metastamirs is still limited. Based on microRNA microarray analyses from normal (n=12) and cancerous (n=12) samples of ccRCC specimens and from bone metastases (n=9) of ccRCC patients, we identified a set of 57 differentially expressed microRNAs between those three sample groups of ccRCC. A selected panel of 33 miRNAs, including miRNAs reported in the literature as differentially expressed in non-metastatic RCC, was validated by RT-qPCR on 57 clinical samples. 30 of the 33 examined miRNAs were confirmed to be deregulated. A stepwise down-regulated miRNA expression from normal over primary tumor to metastatic tissue samples was found to be typical. 23 miRNAs (miR-10b/-19a/-19b/-20a/-29a/-29b/-29c/-100/-101/-126/-127/-130/-141/-143/-145/-148a/-192/-194/-200c/-210/-215/-370/-514) were down-regulated in metastatic tissue samples in comparison to normal tissue. This down-regulated expression in metastatic tissue was also present in 21 miRNAs except for miR-127 and miR-370. The altered miRNA profiles including the newly identified metastasis-associated miRNAs, the compiled predicted miRNA-target interactions, and the significant correlations of miRNAs which were either lost or newly appeared in the studied sample groups afford a solid basis for further functional analyses of individual miRNAs. In this study, microarray-based profiling was performed from 9 bone metastatic tissue samples from 9 patients with clear cell renal cell carcinoma (ccRCC). For controls, 2 bone metastatic samples from two patients with prostate carcinoma and 5 total RNA pools (2 different pools of total RNAs isolated from malignant renal tissue samples derived from different ccRCC patients; 1 pool from non-malignant renal tissue of ccRCC patients; 2 pools of total RNA both from malignant and non-malignant prostate cancer tissue) were used. In addition, matched malignant (e.g., malignant NC2) and non-malignant (e.g., non-malignant NN1) samples from two independent 12 ccRCC sets were profiled (these samples were previously analyzed on a different Platform in GSE12105). The 2002 TNM System and the 2004 WHO classification was used for staging and grading.
2013-02-26 | E-GEOD-37989 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression profiling of known miRNAs and discovery of novel miRNAs at unprecedented quantitative and qualitative accuracy. Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis Deep sequencing was performed on 22 fresh frozen clear cell renal cell carcinoma (ccRCC), 11 non-tumoral renal cortex (NRC) samples and 2 ccRCC cell lines (n=35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. Those without disease recurrence, with recurrence and with metastatic disease at diagnosis.
2012-06-21 | E-GEOD-37616 | biostudies-arrayexpress
Project description:Non-coding RNAs play an important role in the pathogenesis of human malignancies. So far, microRNAs have been investigated in detail in clear cell renal cell carcinoma, but the knowledge about other small non-coding RNAs like snoRNA, tRNA and piRNA remains small. There is increasing evidence that these non-coding RNAs are also involved in regulation of gene expression, and we therefore performed small RNA sequencing in a cohort of 18 corresponding normal and malignant tissue samples from patients with clear cell renal cell carcinoma. We observed differential expression of microRNAs, but also some dysregulated tRNA and snoRNA in clear cell renal cell carcinoma tissue
2016-10-31 | GSE73342 | GEO
Project description:The majority of metastatic clear cell renal cell carcinoma (ccRCC) patients are treated with tyrosine kinase inhibitors (TKIs) in first line, however, a fraction are refractory to these drugs. MicroRNAs (miRNA) are regulatory molecules that have proven to be accurate biomarkers in cancer. Here we identified miRNA predictive of progressive disease under TKI treatment. Whole miRNA expression was quantified by deep-sequencing in a discovery set of 74 metastatic ccRCC cases uniformly treated with TKIs. Twenty nine miRNAs were found to be differentially expressed in the tumors of patients who progressed under TKI therapy. Among six miRNAs selected for validation, an over-expression of miR-1307-3p, miR-155-5p, miR-221-3p, miR-425-5p and miR-222-3p was confirmed in patients with progressive disease as best response. A 2 miRNA-based classifier could discriminate individuals with progressive disease upon TKI treatment with a better predictive value than clinicopathological risk factors commonly used. miRNAs significantly associated with progression-free survival and overall survival were identified, and 7 miRNAs were found to overlap as predictive for early progressive disease, PFS and OS.
2017-08-23 | GSE74174 | GEO
Project description:The aim of this study was to investigate the effect of VEGF targeted therapy (sunitinib) on intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mRCC). 138 samples from patients with clear cell renal cell carcinoma, including biological replicates of nephrectomy samples. RNA extracted fresh frozen tissue samples.
2015-05-25 | E-GEOD-65615 | biostudies-arrayexpress
Project description:Novel single cell technologies have paved the way for the characterization and improved biological understanding of clear cell renal cell carcinoma (ccRCC) where the focus has been mostly on the immunological compartments of the tumor microenvironment (TME). However, the identification of metastatic tumor cell clones, and the stromal compartments of TME of untreated ccRCC patients still remains to be elucidated. Here we perform single-cell RNA-sequencing on treatment naive ccRCC and adjacent normal kidney tissue.
2022-08-18 | GSE178481 | GEO
Project description:Mononuclear phagocytes moderate tissue repair, immune activation and tolerance. In the renal tubulo-interstitium, specialized DCs help maintain homeostasis and protect tubuli from immune injury. Human renal cell carcinoma is immunogenic; yet immunotherapies that target T-cell dysfunction show limited clinical efficacy suggesting additional mechanisms of immunoinhibition. We previously described “enriched-in-renal cell carcinoma” (erc)DCs. In tumor tissue, they are found in tight contact with T cells which are dysfunctional. Here we describe that ercDCs exhibit a distinct polarization state imparted by tissue-specific signals characteristic for ccRCC and renal tissue homeostasis. The resulting mosaic transcript signature includes features associated with host defense activity, angiogenesis/invasion and T-cell inhibition. An ercDC-specific profile was predictive for patient survival and suggests potential therapeutic targets for improved immunotherapy.
2019-12-31 | GSE108311 | GEO
Project description:Mononuclear phagocytes moderate tissue repair, immune activation and tolerance. In the renal tubulo-interstitium, specialized DCs help maintain homeostasis and protect tubuli from immune injury. Human renal cell carcinoma is immunogenic; yet immunotherapies that target T-cell dysfunction show limited clinical efficacy suggesting additional mechanisms of immunoinhibition. We previously described “enriched-in-renal cell carcinoma” (erc)DCs. In tumor tissue, they are found in tight contact with T cells which are dysfunctional. Here we describe that ercDCs exhibit a distinct polarization state imparted by tissue-specific signals characteristic for ccRCC and renal tissue homeostasis. The resulting mosaic transcript signature includes features associated with host defense activity, angiogenesis/invasion and T-cell inhibition. An ercDC-specific profile was predictive for patient survival and suggests potential therapeutic targets for improved immunotherapy.
2019-12-31 | GSE108310 | GEO