Circulating large extracellular vesicles carrying CA9 in the diagnosis and prognosis of clear-cell renal cell carcinoma.
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ABSTRACT:
SUBMITTER: Vergori L
PROVIDER: S-EPMC8002908 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and aimsAlcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as biomarkers for many diseases and are also implicated in the pathogenesis of AH. Therefore, we investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects.Approach and resultsEVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end-stage liver disease (ESLD) attributed to cholestatic liver diseases and nonalcoholic steatohepatitis, decompensated alcohol-associated cirrhosis (AC), and AH. Sphingolipids were quantified by tandem mass spectroscopy. The median plasma EV concentration was significantly higher in AH subjects (5.38 × 1011 /mL) compared to healthy controls (4.38 × 1010 /mL; P < 0.0001), heavy drinkers (1.28 × 1011 /mL; P < 0.0001), ESLD (5.35 × 1010 /mL; P < 0.0001), and decompensated AC (9.2 × 1010 /mL; P < 0.0001) disease controls. Among AH subjects, EV concentration correlated with Model for End-Stage Liver Disease score. When EV counts were dichotomized at the median, survival probability for AH subjects at 90 days was 63.0% in the high-EV group and 90.0% in the low-EV group (log-rank P value = 0.015). Interestingly, EV sphingolipid cargo was significantly enriched in AH when compared to healthy controls, heavy drinkers, ESLD, and decompensated AC (P = 0.0001). Multiple sphingolipids demonstrated good diagnostic and prognostic performance as biomarkers for AH.ConclusionsCirculating EV concentration and sphingolipid cargo signature can be used in the diagnosis and differentiation of AH from heavy drinkers, decompensated AC, and other etiologies of ESLD and predict 90-day survival permitting dynamic risk profiling.
| S-EPMC7541595 | biostudies-literature
Project description:Background: Renal cell carcinoma (RCC) accounts for about 2% of all cancers. Renal biopsy is the gold standard among the diagnostic tools, but it is invasive and not suitable for all patients. Therefore, new reliable and non-invasive biomarkers for ccRCC detection are required. Secretion of extracellular vesicles (EVs), containing RNA molecules that can be transferred between cells, seems to be a general characteristic of malignant transformation. Consistently, cancer-derived EVs are enriched in the blood, urine and various malignant effusions of cancer patients. Therefore, urinary samples can be a non-invasive approach for discovering diagnostic biomarkers. Methods: We enrolled 33 clear-cell RCC (ccRCC) patients and 22 healthy subjects (HS), age and sex-matched, for urine collection and extracellular vesicles isolation by differential centrifugation. Transcriptional profiles of urinary EVs from 12 patients with ccRCC and 11 HS were generated using the Illumina HumanHT-12 v4 BeadChip oligonucleotide arrays. Microarray analysis led to the identification of RNA that were then validated using RT-qPCR. Results: We showed for the first time that urinary exosomal shuttle RNA (esRNA) was significantly different in ccRCC patients compared to HS and we identified three EVs esRNA involved in the tumor biology that are potentially suitable as non-invasive biomarkers. GSTA1, CEBPA and PCBD1 RNA levels decreased in urinary EVs of patients compared to HS. After 1 month post-operation, the levels of RNA increased to reach the normal level. Conclusions: This study suggests, for the first time, the potential use of the RNA content of urinary EVs to provide a non-invasive first step to diagnose the ccRCC. Total RNA obtained from urinary extracellular vesicles isolated from ccRCC patients and healthy subjects.
2016-09-01 | E-GEOD-72922 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) accounts for more than 2% of neoplasias in humans worldwide. Renal biopsy is the gold standard among the diagnostic procedures, but it is invasive and not suitable for all patients. Therefore, new reliable and non-invasive biomarkers for RCC are required. Secretion of extracellular vesicles (EVs), containing RNA molecules that can be transferred between cells, appears to be a common feature of neoplasia. Consistently, cancer-derived EVs are increased in blood and urine. Therefore, urinary samples may be a non-invasive approach for discovering new diagnostic biomarkers. We enrolled 46 patients of whom 33 with clear cell renal cell carcinoma (ccRCC) and 22 healthy subjects (HS). Urinary EVs were isolated by differential centrifugation. Microarray analysis led to the identification of RNA molecules that were validated using RT-qPCR. We found that urinary exosomal shuttle RNA (esRNA) pattern was significantly different in ccRCC patients compared to HS and to non-clear cell RCC (non-ccRCC) and we identified three esRNAs involved in the tumor biology that may be potentially suitable as non-invasive gene signature. GSTA1, CEBPA and PCBD1 esRNA levels were decreased in urine of patients compared with HS. This pattern was specific of the ccRCC and one month after partial or radical nephrectomy the esRNA levels increased to reach the normal level. This study suggests, for the first time, the potential use of the RNA content of urinary EVs to provide a non-invasive first step to diagnose the ccRCC.
| S-EPMC5118659 | biostudies-literature
Project description:Background: Renal cell carcinoma (RCC) accounts for about 2% of all cancers. Renal biopsy is the gold standard among the diagnostic tools, but it is invasive and not suitable for all patients. Therefore, new reliable and non-invasive biomarkers for ccRCC detection are required. Secretion of extracellular vesicles (EVs), containing RNA molecules that can be transferred between cells, seems to be a general characteristic of malignant transformation. Consistently, cancer-derived EVs are enriched in the blood, urine and various malignant effusions of cancer patients. Therefore, urinary samples can be a non-invasive approach for discovering diagnostic biomarkers. Methods: We enrolled 33 clear-cell RCC (ccRCC) patients and 22 healthy subjects (HS), age and sex-matched, for urine collection and extracellular vesicles isolation by differential centrifugation. Transcriptional profiles of urinary EVs from 12 patients with ccRCC and 11 HS were generated using the Illumina HumanHT-12 v4 BeadChip oligonucleotide arrays. Microarray analysis led to the identification of RNA that were then validated using RT-qPCR. Results: We showed for the first time that urinary exosomal shuttle RNA (esRNA) was significantly different in ccRCC patients compared to HS and we identified three EVs esRNA involved in the tumor biology that are potentially suitable as non-invasive biomarkers. GSTA1, CEBPA and PCBD1 RNA levels decreased in urinary EVs of patients compared to HS. After 1 month post-operation, the levels of RNA increased to reach the normal level. Conclusions: This study suggests, for the first time, the potential use of the RNA content of urinary EVs to provide a non-invasive first step to diagnose the ccRCC.
2016-09-01 | GSE72922 | GEO
Project description:Autophagy can protect cells and organisms from stressors such as nutrient deprivation, and is involved in many pathological processes including human cancer. Therefore, it is necessary to investigate the role of autophagy-related genes (ARGs) in cancer. In this study, we investigated the gene expression of 222 ARGs in 1048 Kidney Renal Clear Cell Carcinoma (KIRC) cases, from 5 independent cohorts. The gene expression of ARGs were first evaluated in the The Cancer Genome Atlas (TCGA) by Recevier Operating Characteristic (ROC) analysis to select potential biomarkers with extremely high ability in KIRC detection (AUC?0.85 and p<0.0001). Then in silico procedure progressively leads to the selection of two genes in a three rounds of validation performed in four human KIRC-patients datasets including two independent Gene Expression Omnibus (GEO) datasets, Oncomine dataset and Human Protein Atlas dataset. Finally, only P4HB (Prolyl 4-hydroxylase, beta polypeptide) gene was experimentally validated by RT-PCR between control kidney cells and cancer cells. Following univariate and multivariate analyses of TCGA-KIRC clinical data showed that P4HB expression is an independent prognostic indicator of unfavorable overall survival (OS) for KIRC patients. Based on these findings, we proposed that P4HB might be one potential novel KIRC diagnostic and prognostic biomarker at both mRNA and protein levels.
| S-EPMC7053637 | biostudies-literature
Project description:The ever-increasing morbidity and mortality of clear cell renal cell carcinoma (ccRCC) urgently demands updated biomarkers. MicroRNAs (miRNAs) are involved in diverse biological processes such as cell proliferation, differentiation, apoptosis by regulating their target genes' expression. In kidney cancers, miRNAs have been reported to be involved in tumorigenesis and to be the diagnostic, prognostic, and therapeutic response biomarkers. Here, we performed a systematic analysis for ccRCC-related miRNAs as biomarkers by searching keywords in the NCBI PubMed database and found 118 miRNAs as diagnostic biomarkers, 28 miRNAs as prognostic biomarkers, and 80 miRNAs as therapeutic biomarkers in ccRCC. miRNA-21, miRNA-155, miRNA-141, miRNA-126, and miRNA-221, as significantly differentially expressed miRNAs between cancer and normal tissues, play extensive roles in the cell proliferation, differentiation, apoptosis of ccRCC. GO and KEGG enrichment analysis of these miRNAs' target genes through Metascape showed these target genes are enriched in Protein Domain Specific Binding (GO:0019904). In this paper, we identified highly specific miRNAs in the pathogenesis of ccRCC and explored their potential applications for diagnosis, prognosis, and treatment of ccRCC.
| S-EPMC7746831 | biostudies-literature
Project description:Clear cell renal cell carcinoma (ccRCC) is the most common histological type of renal carcinoma and has a high recurrence rate and poor outcome. Accurate patient risk stratification based on genetic markers can help to identify the high-risk patient for early and further treatments and would promote patient survival. Long non-coding RNAs (lncRNAs) have attracted widespread attention as biomarkers for early diagnosis, treatment, and prognosis because of their high specificity and sensitivity. Here, we performed a systematic search in NCBI PubMed and found 44 lncRNAs as oncogenes, 18 lncRNAs as tumor suppressors, 199 lncRNAs as diagnostic biomarkers, 62 lncRNAs as prognostic biomarkers, and 3 lncRNAs as predictive biomarkers for ccRCC. We also comprehensively discuss the biological functions and molecular regulatory mechanisms of lncRNAs in ccRCC. Overall, the present study is a systemic analysis to assess the expression and clinical value of lncRNAs in ccRCC, and lncRNAs hold promise to be diagnostic, prognostic, and predictive biomarkers.
| S-EPMC8424129 | biostudies-literature
Project description:What is the leading molecular mechanism that causes broad resistance to systemic therapies remains a key question in renal cancer related research. We explored associations of TRIP13 expression with the clinical course using the tissue microarray (TMA). The TMA contained specimens from 87 patients diagnosed with clear cell renal cell carcinoma (ccRCC). We performed immunohistochemistry to investigate TRIP13 protein expression levels. The overall survival (OS) was analyzed using the Kaplan-Meier method and log-rank statistics. Univariate and multivariate analyses were conducted using Cox proportional hazard models. Median follow up for the TMA cohort was 7.0 years. Tissues from 28.74% of patients demonstrated high TRIP13 expression. Mean TRIP13 expression in TRIP13-rich tumors was significantly higher comparing to adjacent normal tissues (P < 0.05). TRIP13 expression did not significantly correlate with stage nor tumor grade (P > 0.05). Elevated expression of TRIP13 served as an independent unfavorable prognostic indicator of survival in ccRCC (P < 0.05). TRIP13 overexpression predicts poor prognosis in ccRCC. Together with the emerging reports, this observation raises a suspicion that TRIP13 is a substantial driver of resistance to systemic therapies against kidney cancer.
| S-EPMC7539765 | biostudies-literature
Project description:Most cancer-related deaths are caused by distant metastases, which are tumour cells that have escaped from a primary tumour and passed into the bloodstream to colonize a new organ. In this context, communication between tumour and stromal cells is essential. Indeed, tumor cells interact with cells in the tumor microenvironment and are able to modify them to their advantage. Both extracellular vesicles (EVs) and exosomes are heterogeneous populations of small vesicles present in the tumor microenvironment and in body fluids that have recently emerged as powerful mediators involved in this communication and their transport in fluids. Tumor cells release large quantities of exosomes containing tumor markers, which can then spread to distant locations.
The exosomes are of endosomal origin. They are composed of proteins, lipids, RNA and DNA, and they circulate in the bloodstream. They can be internalized by specific distant cells and thus deliver a functional message. It has recently been shown that tumor exosomes containing pro-metastatic factors form pre-metastatic niches, before the tumor cells actually arrive, while determining the metastatic organotropism of tumors. These properties are now opening up new avenues of research in tumor biomarkers. In recent years, several studies have highlighted different markers contained specifically in exosomes derived from cancer cells. Consequently, exosomes are considered as potential reservoirs of tumor biomarkers that could be clinically useful for the non-invasive diagnosis of cancer, with the advantage of being performed by liquid biopsy. The study of microRNA (miRNA) is of particular interest. Indeed, miRNAs are small non-coding RNAs (between 21 and 25 nucleotides) involved in the regulation of gene expression and which are frequently deregulated in cancer. Several studies underline that the variation of free miRNAs in the blood is correlated with the progression of the disease, particularly in colon cancer. However, the stability of free miRNAs is controversial. Therefore, exosomes represent a very advantageous means of transporting miRNAs in the blood, as they are able to protect miRNAs from degradation by RNAase.
The hypothesis of the project is that circulating exosomes derived from tumours contain markers including specific miRNAs that could be used as biomarkers of early prognosis (survival and progression), easily measured in blood samples from patients with colon cancer. But other molecules contained in exosomes could also be of interest.
| 2349603 | ecrin-mdr-crc
Project description:Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that the immune-related gene (IRG) hematopoietic cell signal transducer (HCST) could provide guidance for the diagnosis, prognosis, and treatment of ccRCC. The RNA-seq data of ccRCC tissues were extracted from two databases: TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/). Corresponding clinical information was downloaded from TCGA. Immune-related gene data were extracted from the IMMPORT website (https://www.immport.org/). Differential analysis with R software (https://www.r-project.org/) was used to obtain a prognosis model of ccRCC IRGs. The differences were combined with the clinical data to assess the usefulness of the HCST as a prognostic biomarker. Based on data obtained from the Oncomine (https://www.oncomine.org/), Human Protein Atlas (https://www.proteinatlas.org/), and PubMed (https://pubmed.ncbi.nlm.nih.gov/) databases, the expression levels of the HCST in ccRCC, clinical-pathological indicators of relevance, and influence on prognosis were analyzed. Regulation of the HCST gene in ccRCC was assessed by gene set enrichment analysis (GSEA). In TCGA/GEO databases, the high HCST expression in tumor tissues was significantly correlated to the TMN stage, tumor grade, invasion depth, and lymphatic metastasis (p < 0.05). The overall survival (OS) of patients with high HCST gene expression was significantly lower than that of patients with low HCST gene expression (p < 0.001). Multivariate Cox regression analysis suggested that the HCST expression level [hazard ratio (HR) = 1.630, 95% confidence interval (CI) = 1.042-2.552], tumor cell grade (HR = 1.829, 95% CI = 1.115-3.001), and distant metastasis (HR = 2.634, 95%, CI = 1.562-4.442) were independent risk factors affecting the OS of ccRCC patients (all, p < 0.05). The GSEA study showed that there was significant enrichment in cell adhesion, tumorigenesis, and immune and inflammatory responses in HCST high expression samples. Hematopoietic cell signal transducer expression was closely associated with the levels of infiltrating immune cells around ccRCC tissues, especially dendritic cells (DCs). In conclusion, the present study suggested that the HCST was interrelated to the clinicopathology and poor prognosis of ccRCC. High HCST expression was also closely correlated with the levels of tumor-infiltrating immune cells, especially DCs.
| S-EPMC8103545 | biostudies-literature