Molecular Profiling Reveals Immunosuppressive Tumor Immune Microenvironment in Primary versus Paired Asynchronous Metastatic Clear Cell Renal Cell Carcinoma
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ABSTRACT:
PROVIDER: PRJNA1165804 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30812704_1.fastq.gz | Fastqsanger.gz | |||
| SRR30812704_2.fastq.gz | Fastqsanger.gz | |||
| SRR30812705_1.fastq.gz | Fastqsanger.gz | |||
| SRR30812705_2.fastq.gz | Fastqsanger.gz | |||
| SRR30812706_1.fastq.gz | Fastqsanger.gz |
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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
Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues.
2015-10-26 | GSE61441 | GEO
Project description:Genome wide DNA methylation profiling of clear cell renal cell carcinoma (ccRCC) tissue versus matched normal kidney tissue. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumor and adjacent normal kidney tissue samples from ccRCC patients. Samples included 46 paired fresh frozen ccRCC tumor and adjacent normal kidney tissues. Bisulphite converted DNA from the 92 samples were hybridised to the Illumina Infinium 450 Human Methylation Beadchip v1.2
2015-10-26 | E-GEOD-61441 | biostudies-arrayexpress
Project description:<p>The ultimate goal of surgical treatment in cancer is to remove the tumor mass for restoring a healthy state. A 16-lipid panel that discriminated healthy controls from clear cell renal cell carcinoma (ccRCC) patients in a prior study was evaluated in the present work in paired-serum samples collected from patients (n = 41) before and after nephrectomy. Changes in the lipid and metabolite fingerprints from ccRCC patients were investigated and compared with fingerprints from healthy individuals obtained by means of ultra-performance liquid chromatography-high-resolution mass spectrometry. The lipid panel differentiated phenotypes associated with metabolic restoration after surgery, representing a serum signature of phenoreversion to a healthy metabolic state. In particular, PC 16:0/0:0, PC 18:2/18:2 and linoleic acid allowed discriminating serum samples from ccRCC patients with poor prognosis from those with an improved outcome during the follow-up period. Ratios of PC 16:0/0:0 and PC 18:2/18:2 with linoleic acid levels may contribute as prognostic tools to support decision-making during the patient follow-up care. The preliminary character of these results should be validated with larger cohorts, including subjects with different ethnicities, life style and diets.</p>
2023-01-02 | MTBLS3838 | MetaboLights
Project description:Intragraft transcriptional profiles were investigated in patients with tubular dysfunction to disclose subclinical mechanisms underlying graft deterioration. Moreover, we analyzed whether individualization of immunosuppression could modify this profile while improving renal function after 12 months of regimen modification. 33 renal transplant patients were enrolled in the study considering their high urinary levels of retinol binding protein, a biomarker of proximal tubular dysfunction (PTD). They were divided in two groups regarding immunosuppressive therapy. At time zero (t0), 33 patients were biopsied and 18 patients had their immunosuppression regimen modified, namely, reduction of cyclosporine dosage and introduction of mycophenolate mofetil (MYF), while 15 patients remained under azathioprine (AZA) schema. All patients were followed-up for 12 months (t12) and then re-biopsied. Microarray experiments were performed using biopsies from 17 patients. Molecular changes due to elevated uRBP levels and immunosuppressive therapies were interpreted via transcriptional network analysis. This dataset is part of the TransQST collection.
2015-07-31 | E-GEOD-48250 | biostudies-arrayexpress
Project description:BackgroundThe association between ccRCC and Anoikis remains to be thoroughly investigated.MethodsAnoikis-related clusters were identified using NMF. To identify prognostic anoikis-related genes (ARGs) and establish an optimal prognostic model, univariate Cox and LASSO regression were employed. The E-MTAB-1980 cohort was utilized for external validation. Multiple algorithms were used to evaluate the immune properties of the model. GO, KEGG and GSVA analyses were employed to analyze biological pathway functions. qRT-PCR was employed to measure RNA levels of specific genes. Cell Counting Kit-8, wound healing, and Transwell chamber assays were performed to determine changes in the proliferative and metastatic abilities of A498 and 786-O cells.ResultsBased on the expression of 21 prognostic ARGs, we constructed anoikis-related clusters with different prognostic and immune characteristics. The cluster A1 showed a worse prognosis, higher infiltration of immunosuppressive cells and enrichment of several oncogenic pathways. We also calculated the Anoikis Index (AI). Patients in high AI group had a worse prognosis, higher infiltration of immunosuppressive cells and higher expression of immunosuppressive checkpoints. TIMP1 exerted a tumor-promoting role in ccRCC and was significantly associated with immunosuppressive cells and checkpoints. The downregulation of TIMP1 negatively regulated ccRCC cell proliferation and metastasis.ConclusionsARGs played crucial roles in tumorigenesis and progression and were positively associated with a poor prognosis. AI had great accuracy in predicting the prognosis and immune characteristics of ccRCC patients. TIMP1 was significantly associated with clinicopathological variables and the immunosuppressive microenvironment, which could be exploited to design novel immunotherapies for ccRCC patients.
| S-EPMC10522382 | biostudies-literature
Project description:Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor and immune dysfunction is associated with ccRCC poor prognosis. The RhoGTPase-activating proteins (RhoGAPs) family was reported to affect ccRCC development, but its role in immunity and prognosis prediction for ccRCC remain unknown. In the current study, we found ARHGAP11A was the only independent risk factor among 33 RhoGAPs (hazard ratio [HR] 1.949, 95% confidence interval [CI] 1.364-2.785). High ARHGAP11A level was associated with shorter overall survival (OS, HR 2.040, 95% CI 1.646-3.417) and ARHGAP11A is a prognostic biomarker for ccRCC. ARHGAP11A knockdown suppressed renal cell carcinoma (RCC) cell proliferation, colony formation, and migration, suggesting the promoting role of ARHGAP11A on RCC development. Mechanistically, ARHGAP11A might contribute to the suppressive tumor immune microenvironment (TIME). High ARHGAP11A level was correlated with infiltration of immunosuppressive cells (including T helper 2 (Th2) cells, regulatory T (Treg) cells, myeloid derived suppressor cells (MDSC), and M2 macrophage cells), activation of immunosuppressive pathways (IL6-JAK-STAT3 signaling and IFNγ response), and expression of inhibitory immune checkpoints (ICs). ARHGAP11A could promote T cell exhaustion and induce immune escape. ccRCC patients with low ARHGAP11A level were more suitable for immune checkpoint inhibitors (ICIs) therapy, while those with high ARHGAP11A level might benefit from a combination of ARHGAP11A blockade and ICIs. In all, ARHGAP11A might serve as a novel prognostic marker, therapeutic target, and predictor in the clinical response to ICIs therapy for ccRCC.
| S-EPMC10178328 | biostudies-literature
Project description:We analyzed 84 tumor/normal pairs (177 total) using standard shotgun proteomic techniques in order to characterize the molecular landscape of clear cell renal cell carcinoma (ccRCC) and interrogated changes in protein abundance and biological pathways with ccRCC grade. These tissues were distributed across stage 1 (n = 34), 2 (n = 40), 3 (n = 42), and 4 (n = 52), with 9 pairs also including samples from metastasized tumor. These data can be (and were) combined with a previously published transcriptomic data set from the same sample cohort (NCBI GEO: GSE53757).
2016-04-18 | PXD003271 | Pride
Project description:ObjectivesPrevious studies noted discordance of programmed death-1 (PD-1) and one of its ligands (PD-L1) across patient-matched primary and metastatic clear cell renal cell carcinoma (ccRCC). There are inconsistencies if the primary or metastatic tumor has higher expression, and whether metastatic tumor expression is associated with patient outcome. Thus, we examined PD-1 and PD-L1 in patient-matched tumors using a large number of ccRCC patients with long follow-up.Materials and methodsWe analyzed PD-1 and PD-L1 using immunohistochemistry in patient-matched primary and metastatic tumors from 110 ccRCC patients. Concordance was assessed among longitudinal metastatic tumors, as well as across patient-matched primary and metastatic tumors. Cox proportional hazards regression was used to evaluate the associations of metastatic tumor expression with cancer-specific survival.ResultsWe observed inter-metastatic tumor heterogeneity of PD-1 in 25 (69%) of the 36 patients and of PD-L1 in seven (19%) patients. Concordance between patient-matched primary and metastatic tumors was 73% (Kappa = 0.16, 95% CI: -0.003-0.32). Similarly, concordance of PD-L1 between metastatic and patient-matched primary tumors was 78% (Kappa = 0.27, 95% CI: 0.09-0.46). Both markers demonstrated higher expression in primary vs metastatic tumors. Metastatic tumor expression of PD-1 was significantly associated with metastatic location (P < .0001) and ccRCC-specific survival (HR = 2.15, 95% CI: 1.06-4.36, P = .035).ConclusionsThe expression of PD-1 and PD-L1 is discordant across patient-matched ccRCC tumors, with higher expression in primary tumors. Higher PD-1 expression was associated with metastatic location and lower cancer-specific survival. If validated, these results highlight the importance of evaluating these biomarkers in metastatic tissue specifically.
| S-EPMC6997072 | biostudies-literature
Project description:In sporadic clear cell renal cell carcinoma (CCRCC), the von Hippel Lindau (VHL) gene is inactivated by mutation or methylation in the majority of primary (P) tumors. Due to differing effects of wild-type (WT) and mutant (MT) VHL gene on downstream signaling pathways regulating angiogenesis, VHL gene status could impact clinical outcome. In CCRCC, comparative genomic hybridization analysis studies have reported genetic differences between paired P and metastatic (M) tumors. We thus sequenced the VHL gene in paired tumor specimens from 10 patients to determine a possible clonal relationship between the P tumor and M lesion(s) in patients with CCRCC. Using paraffin-embedded specimens, genomic DNA from microdissected samples (>80% tumor) of paired P tumor and M lesions from all 10 patients, as well as in normal tissue from 6 of these cases, was analyzed. The DNA was used for PCR-based amplification of each of the 3 exons of the VHL gene. Sequences derived from amplified samples were compared to the wild-type VHL gene sequence (GenBank Accession No. AF010238). Methylation status of the VHL gene was determined using VHL methylation-specific PCR primers after DNA bisulfite modification. In 4/10 (40%) patients the VHL gene status differed between the P tumor and the M lesion. As expected, when the VHL gene was mutated in both the P tumor and M lesion, the mutation was identical. Further, while the VHL genotype differed between the primary tumor in different kidneys or multiple metastatic lesions in the same patient, the VHL germline genotype in the normal adjacent tissue was always wild-type irrespective of the VHL gene status in the P tumor. These results demonstrate for the first time that the VHL gene status can be different between paired primary and metastatic tissue in patients with CCRCC.
| S-EPMC3361062 | biostudies-literature