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A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma

ABSTRACT: A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma

PROVIDER: PRJNA423067 | ENA |

REPOSITORIES: ENA

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A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma [in vitro]

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

A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma [ex vivo]

2019-12-31 | GSE108310 | GEO

A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma [in vitro]

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

A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma [ex vivo]

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

A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-31 | GSE108312 | GEO

Downregulation of PPA2 expression correlates with poor prognosis of kidney renal clear cell carcinoma.

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

Low DAPK1 expression correlates with poor prognosis and sunitinib resistance in clear cell renal cell carcinoma.

Project description:We investigated the prognostic significance of Death-Associated Protein Kinase 1 (DAPK1) and its role in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). DAPK1 mRNA levels were significantly lower in tumor tissues than normal kidney tissues in TCGA-KIRC dataset (n=428). Both overall survival and disease-free survival were significantly shorter in ccRCC patients with low DAPK1 expression than those with high DAPK1 expression. Receiver operating characteristic curve analysis showed that low DAPK1 expression correlated with poor prognosis in ccRCC patients. Multivariate analysis confirmed that DAPK1 expression was an independent prognostic indicator in ccRCC. Gene set enrichment analysis showed that low DAPK1 expression correlates with upregulation of pathways related to metastasis, drug resistance, hypoxia and invasiveness in ccRCC patients. Sunitinib-resistant ccRCC cells show significantly lower DAPK1 mRNA and protein levels than sunitinib-sensitive ccRCC cells. DAPK1 overexpression enhances apoptosis in sunitinib-resistant ccRCC cells via the ATF6-dependent ER stress pathway. Xenograft tumors derived from DAPK1-overxpressing ccRCC cells were significantly smaller than the controls in nude mice. Our finding demonstrates that low DAPK1 expression is an independent prognostic indicator that correlates with ccRCC progression and sunitinib resistance.

| S-EPMC7880360 | biostudies-literature

Nuclear localization of the CK2α-subunit correlates with poor prognosis in clear cell renal cell carcinoma.

Project description:Protein kinase CK2α, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2α expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC). Also the kinase activity of CK2 was significantly increased in ccRCC compared to normal renal cortex. Nuclear protein expression of CK2α correlated in univariate analysis with poor Progression Free Survival (HR = 8.11, p = 0.016). Functional analyses (cell proliferation assay) revealed an inhibitory effect of Caki-2 cell growth following CK2 inhibition with CX-4945. Our results suggest that CK2α promotes migration and invasion of ccRCC and therefore could serve as a novel prognostic biomarker and molecular therapeutic target in this type of cancer.

| S-EPMC5352082 | biostudies-literature

Clear-cell renal cell carcinomas tumors

Project description:Whole genome expression of 39 clear-cell renal cell carcinomas tumors 39 frozen tissue from recent nephrectomies for clear-cell renal cell carcinoma; association with clinical characteristics

2011-05-28 | E-GEOD-29609 | biostudies-arrayexpress

Reduced GRAMD1C expression correlates to poor prognosis and immune infiltrates in kidney renal clear cell carcinoma.

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

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