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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
Project description:A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma
| PRJNA423067 | ENA
Project description:A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma [in vitro]
| PRJNA423142 | ENA
Project description:A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma [ex vivo]
| PRJNA423143 | ENA
Project description:Background: Specific lifestyle factors including tobacco-exposure are vital etiologic factors for renal cell carcinoma (RCC), F2R Like Thrombin/Trypsin Receptor 3 (F2RL3) is associated with smoking but it is unknown whether its expression translate into poor survival of clear cell RCC (ccRCC). In the current study, the expression profiling and prognostic value of F2RL3 in Chinese patients with ccRCC were investigated. Methods: Using Quantitative PCR analysis and immunohistochemistry, the relative expression levels of F2RL3 in 367 paired ccRCC and adjacent normal tissues were calculated. Cox regression analysis was used to identify independent prognostic factors and Kaplan-Meier analysis and a log-rank test were employed to evaluate the prognostic value of F2RL3. Results: We observed that high expression of F2RL3 mRNA and protein were strongly correlated with shorten progression-free survival (PFS) of ccRCC with hazard ratios (HR; 95% confidence interval (CI)) of 2.060 (1.410-3.009) and 1.657 (1.193-2.300), respectively, as well as with poor overall survival (OS) with HRs (95%CI) of 2.826 (1.713-4.662) and 1.712 (1.140-2.569), respectively. After adjustment for confounding factors including smoking status, elevated HRs (95%CI) of 2.113 (1.445-3.089) and 1.692 (1.218-2.352) were presented for PFS, respectively, and 2.936 (1.777-4.851) and 1.811 (1.203-2.725) were present for OS, respectively. Meanwhile, increased F2RL3 mRNA and protein level were reported to significantly associate with smoking-exposure and well-known prognostic factors (higher TNM stage and ISUP grade). Conclusion: These findings suggested that F2RL3 mRNA and protein level in ccRCC is a robust predictor of poorly prognostic phenotype. Exploring the causal relevance of F2RL3 in ccRCC development further warrants in the future study.
| S-EPMC6160688 | biostudies-literature
Project description:BackgroundKidney renal clear cell carcinoma (KIRC) is the most common subtype of kidney cancer. Inorganic pyrophosphatase (PPA2) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate; few studies have reported its significance in cancers. Therefore, we aimed to explore the prognostic value of PPA2 in KIRC.MethodsPPA2 expression was detected via immunohistochemistry in a tissue chip containing specimens from 150 patients with KIRC. We evaluated the correlation between PPA2 expression, clinicopathological characteristics, and survival. Data from online databases and another cohort (paraffin-embedded specimens from 10 patients with KIRC) were used for external validation.ResultsPPA2 expression was significantly lower in KIRC tissues than in normal renal tissues (p < 0.0001). Low expression of PPA2 was significantly associated with a high histologic grade and poor prognosis. The differential expression of PPA2 was validated at the gene and protein levels. Multivariate Cox regression analysis showed that PPA2 expression was an independent prognostic factor in patients with KIRC. Gene set enrichment analysis suggested that decreased expression of PPA2 might be related to the epithelial-mesenchymal transition in KIRC.ConclusionsOur study demonstrated that PPA2 is an important energy metabolism-associated biomarker correlated with a favorable prognosis in KIRC.
| S-EPMC8428262 | biostudies-literature
Project description:MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 was significantly downregulated in 87.8% renal cancer samples compared with corresponding noncancerous tissues (NCT), which was significantly associated with clinical stage, T classification and poor overall survival. Functional study demonstrated that enforced overexpression of miR-1 in renal cancer cells inhibited proliferation and metastasis in vitro and in vivo. Conversely, miR-1 inhibitor silencing miR-1 expression promoted cell proliferation and metastasis in ccRCC. CDK4, CDK6, Caprin1 and Slug were each directly targeted for inhibition by miR-1 and restoring their expression reversed miR-1-mediated inhibition of cell cycle progression and metastasis. Taken together, our findings established a tumor suppressive role for miR-1 in the progression of ccRCC by targeting CDK4, CDK6, Caprin1 and Slug and suggested miR-1 can be served as a novel potential therapeutic target for ccRCC.
| S-EPMC4537008 | biostudies-other
Project description:Loss of chromosome 14 has been associated with poor outcomes in clear-cell renal cell carcinoma. Expression of HIF? isoforms has been linked to distinct molecular phenotypes of clear-cell renal cell carcinoma. We hypothesized that chromosome 14 loss could lead to a decrease in HIF1? levels, as its gene (HIF1A) resides in this chromosome. We analyzed 112 archival clear-cell renal cell carcinoma tumor specimens with 250K SNP microarrays. We also evaluated expression of HIF? isoforms by qPCR and immunohistochemistry in a subset of 30 patients. Loss of chromosome 14q was associated with high stage (III-IV, P=0.001), high risk for recurrence (P=0.002, RR 2.78 (1.506-5.153)) and with decreased overall survival (P=0.030) in non-metastatic clear-cell renal cell carcinoma. HIF1? mRNA and protein expression was reduced in specimens with loss of 14q (P=0.014) whereas HIF2? was not. Gain of 8q was associated with decreased overall survival (P<0.0001). Our studies confirm an association between 14q loss and clinical outcome in non-metastatic clear-cell renal cell carcinoma patients and that 8q gain is a candidate prognostic marker for decreased overall survival and appears to further decrease survival in patients with 14q loss. We have also identified that differential expression of HIF1? is associated with 14q loss. Further exploration of 8q gain, 14q loss, MYC, HIF1A and EPAS1 (HIF2?) as molecular markers of tumor behavior and prognosis could aid in personalizing medicine for patients with clear-cell renal cell carcinoma.
| S-EPMC4639322 | biostudies-literature
Project description:There has been an increase in the mortality rate and morbidity of kidney cancer (KC) with kidney renal clear cell carcinoma (KIRC) being the most common subtype of KC. GRAMD1C (GRAM Domain Containing 1C) has not been reported to relate to prognosis and immunotherapy in any cancers. Using bioinformatics methods, we judged the prognostic value of GRAMD1C expression in KIRC and investigated the underlying mechanisms of GRAMD1C affecting the overall survival of KIRC based on data downloaded from The Cancer Genome Atlas (TCGA). The outcome revealed that reduced GRAMD1C expression could be a promising predicting factor of poor prognosis in kidney renal clear cell carcinoma. Meanwhile, GRAMDIC expression was significantly correlated to several tumor-infiltrating immune cells (TIICs), particularly the regulatory T cells (Tregs). Furthermore, GRAMD1C was most significantly associated with the mTOR signaling pathway, RNA degradation, WNT signaling pathway, toll pathway and AKT pathway in KIRC. Thus, GRAMD1C has the potential to become a novel predictor to evaluate prognosis and immune infiltration for KIRC patients.
| S-EPMC6927341 | biostudies-literature