Identification of metastasis associated genes in clear cell renal cell carcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: xu zhang
PROVIDER: E-GEOD-47352 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This study investigates the genes that promote clear cell renal cell carcimoma (ccRCC) metastasis using 4 primary metastatic and 5 non-metastatic tumor samples. U133 plus 2.0 array was used to identify the diffrently expressed genes between the primary metastatic and non metastatic ccRCC samples
2013-05-25 | GSE47352 | 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:A total of 3 metastatic and 3 non-metastatic ccRCC tissues were collected from patients. These tissues were flash frozen in liquid nitrogen immediately after surgery and subsequently stored at -80℃. All the resected nodules or metastatic masses were identified as renal tumor by pathologic examination. No patients received anticancer treatments before surgery in this study. We analyzed gene expression microarray data from our gene chip with 3 metastatic ccRCC tissues compared with 3 non-metastatic ccRCC tissues.
2017-08-17 | GSE88948 | GEO
Project description:Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.
2023-12-18 | GSE245372 | GEO
Project description:The understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. This comprises the extremely varying dormancy periods of tumor cells in the secondary organ after metastatic spread, represented by the disease-free survival (DFS) of the patients, or differing numbers of metastases in different patients. Knowing the molecular fundamentals of these phenomena would support the individual prediction of patients´ outcome and facilitate the decision for an appropriate monitoring and therapy regime. In a first study (PMID 19391132) we analyzed the transcriptome-wide expression profiles of 20 pulmonary metastases of renal cell carcinoma (Met1-9, Met11-18, Met20, Met23, Met25) to identify expression patterns associated with the dormancy period and the number of metastases per patient. Pre-processed and analyzed data for this study are available in GEO Series GSE14378. In this second study, we validated the DFS-associated expression pattern from the first study on four further metastases and also included primary ccRCC with different DFS. For this, the microarray data of all metastases and primary tumors were pre-processed together. The aim of this second study was to identify those genes, which are differentially expressed in metastases developed after different dormancy periods and which are already deregulated in primary tumors. Genes differentially expressed in synchronously vs. metachronously metastases might contribute functionally to the dormancy period. Genes already deregulated in primary ccRCC might be suitable for prognostic purposes. metastases manifested synchronously or metachronously (DFS less than or equal to 9 months compared with DFS greater than or equal to 60 months); primary ccRCC which developed synchronous or metachronous metastases (DFS less than or equal to 6 months compared with DFS greater than or equal to 45 months)
2010-07-30 | E-GEOD-22541 | biostudies-arrayexpress
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.
2013-02-26 | GSE37989 | GEO
Project description:Metastatic clear cell renal cell carcinoma (ccRCC) has a poor prognosis and unpredictable course and there are no molecular markers that reliably predict ccRCC metastasis. In this study, specimens from 84 patients with ccRCC were directly cultured in vitro. The primary cultures from 38 of 94 specimens contained more than 90% tumor cells at 4th passages. After identified by immunostaining, the primary cultures of metastatic- and nonmetastatic ccRCC specimens from the age-, gender-matched patients were subjected to cDNA microrray assays. A total of 842 differentially expressed genes with FDR (false discovery rate) = 4.79% were identified by using SAM (Significance Analysis of Microarray) software. Pathway enrichment and co-occurrence with “cancer”, “metastasis” and “invasion” in the literature annotations enriched the functions of the 842 genes and indicated the reliability of our microarray assays. Novel genes associated with metastasis were selected based on intra-molecular interaction between 205 differentially expressed genes co-occurred with “metastasis” and those not appeared with “metastasis” on Medline, as well as co-expression analysis between 205 differentially expressed genes co-occurred with “metastasis” and those not appeared on Medline in 12 microarray data. FSTL1, AV722783, SLC15A1, DDX17, ORC2L and PKMYT1 were proved to be potential ccRCC metastasis-associated novel genes, based on its expression patterns in the cultures and tumor tissues. Interestingly, the up-regulated genes (CAV1, PKMYT1 and ORC2L) were up-regulated and the down-regulated genes (FSTL1, GSTM3, CYR61, SLC15A1 and AV722783) were down-regulated, in the primary ccRCC specimens as compared with its adjacent normal kidney in 37 patients (determined by semi-quantitative RT-PCR). This study provides potential biomarkers and novel molecular targets for the early diagnosis and treatment of ccRCC metastasis. Keywords: Homo sapiens Because of limited cell number of primary cultures, total RNA of the primary cultures from 2 age and gender matched patients was pooled for each microarray assay. Each assay was technically repeated once. Cy3-labeled 1st cDNA synthesized from total RNA of the metastatic ccRCC pool was mixed with Cy5-labeled 1st cDNA synthesized from total RNA of the non-metastatic ccRCC pool, and hybridized to 16K cDNA chips (GEO Platform ID: GPL6259; SBC-R-HC-100-22, National Engineering Center for Biochip, Shanghai, China) that included 14784 unigenes, 241 negative controls and 527 positive controls. In our study we used a co-expression analysis for the relationship between genes; three gastric cancer Samples were only introduced to this analysis methods.
2008-08-27 | E-GEOD-11072 | biostudies-arrayexpress
Project description:Clear cell renal cell carcinoma is one of the most common diagnostic tumor, with nearly one third patients diagnosed as metastatic ccRCC. Although increasing number of studies have revealed that piwi-interacting RNAs were aberrantly expressed in diverse type of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particular in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC was selected by using piRNA-sequencing combined with analyzing TCGA data, from which piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further studies revealed that piR-57125 modulated ccRCC metastasis through AKT/ERK pathway. Those data indicate that piR-57125 restrains ccRCC metastasis through directly targeting CCL3 and inhibiting AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.
2021-09-08 | GSE183496 | GEO
Project description:Advanced clear cell renal cell carcinoma (ccRCC) frequently causes systemic inflammation. Here, we identified the functional role and regulatory mechanism of inflammation driven by advanced ccRCC cells. The inflammatory nature of advanced ccRCC was recapitulated in a preclinical model of ccRCC. Amplification of cancer cell-intrinsic inflammation during ccRCC progression triggered neutrophil-dependent lung metastasis. Massive expression of inflammation-related genes was transcriptionally activated by epigenetic remodelling through mechanisms such as DNA demethylation and super-enhancer formation. Bromodomain and extra-terminal motif inhibitor (BETi) synchronously suppressed C–X–C-type chemokines in ccRCC cells and decreased neutrophil-dependent lung metastasis. Overall, our findings shed insight into the nature of inflammatory ccRCC, which triggers metastatic cascades, and suggest a potential therapeutic strategy.
2020-10-28 | GSE131137 | GEO
Project description:Clear cell renal cell carcinoma (ccRCC) is a highly immune infiltrated cancer, but how the tumor immune microenvironment (TIME) evolves during disease progression is unknown. Insights into heterogeneity within primary ccRCC raise questions about potential heterogeneity between primary and paired metastatic tumors. This information may improve understanding of immune evasion leading to metastatic disease and response to immunotherapy. In this study, we characterize and compare the TIME of primary ccRCC with paired asynchronous metastases. We demonstrate higher infiltration of immunosuppressive cells in the TIME of primary ccRCC compared with metastatic sites. Further studies are necessary to determine the prognostic and therapeutic significance of these findings. Understanding the heterogeneity of the tumor immune microenvironment in RCC, both intratumorally and between metastatic sites, has important clinical implications for selecting appropriate therapies and developing predictive biomarkers. Future research should focus on elucidating the impact of these findings on immunotherapeutic responses and patient outcomes in ccRCC.
2024-09-27 | GSE278174 | GEO