ArticleCancer cell international2022
KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma.
Article in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- An externally validated lactylation-associated prognostic signature for overall survival prediction in lung adenocarcinoma identifiesTranslational cancer research · 2026Article
- Immune Escape in Renal Cell Carcinoma: Latest Research and Treatment Strategies.International journal of molecular sciences · 2026Review
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- Identification of glycolysis-related genes and analysis of potential prognostic clinical application in oral squamous cell carcinoma.Translational cancer research · 2025Article
- Integrative analysis of ceRNA networks and immune cell infiltration in thyroid cancer for enhanced diagnostic and prognostic insights.Scientific reports · 2025Article
- Construction and validation of a novel prognostic model with palmitoylation-related genes for glioblastoma.Translational cancer research · 2024Article
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- ACYP2 functions as an innovative nano-therapeutic target to impede the progression of hepatocellular carcinoma by inhibiting the activity of TERT and the KCNN4/ERK pathway.Journal of nanobiotechnology · 2024Article
- Identification and analysis of key genes related to efferocytosis in colorectal cancer.BMC medical genomics · 2024Article
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- CVD phenotyping in oncologic disorders: cardio-miRNAs as a potential target to improve individual outcomes in revers cardio-oncology.Journal of translational medicine · 2024Review
- Comprehensive analysis of a tryptophan metabolism-related model in the prognostic prediction and immune status for clear cell renal carcinoma.European journal of medical research · 2024Article
- The RELT Family of Proteins: An Increasing Awareness of Their Importance for Cancer, the Immune System, and Development.Biomedicines · 2023Review
- Identification of the Prognostic Biomarkers CBX6 and CBX7 in Bladder Cancer.Diagnostics (Basel, Switzerland) · 2023Article
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- Risk model-guided identification of MTDH expression as a marker for ferroptosis induction therapy in head and neck squamous cell carcinoma.American journal of cancer research · 2023Article
- Predicting prognosis and immunotherapeutic response of clear cell renal cell carcinoma.Frontiers in pharmacology · 2022Article
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16 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundStudies over the past decade have shown that competitive endogenous RNA (ceRNA) plays an essential role in the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). Meanwhile, immune checkpoint blocker is gradually moving towards the first-line treatment of ccRCC. Hence, it's urgent to develop a new prediction model for the efficiency of immunotherapy. At present, there is no study to reveal the effect of ceRNA network on the efficiency of immunotherapy for ccRCC.
methodsTo systematically analyze the effect of ceRNA hub genes in ccRCCon immune response, we constructed prognosis models based on ceRNAs and immune cells, respectively. We constructed ceRNA network using hypergeometric distribution test and correlation analysis with R script based on The Cancer Genome Atlas (TCGA) database. We then applied the Cibersort algorithm to simulate the infiltration overview of immune cells in kidney renal clear carcinoma (KIRC) samples. Prognosis-related immune cells were screened and a predictive model of these cells was constructed. Prognosis-related immune cells and ceRNA hub genes were performed with co-expression analysis. Finally, qRT-PCR and immunofluorescence assays were performed to validate the results.
resultsThe construction of ceRNA related prognosis model contained 8 hub genes, including RELT, MYO9B, KCNN4, SIX1, OTOGL, MALAT1, hsa-miR-130b-3p, and hsa-miR-21-5p. The area under the receiver operating characteristic curve (AUC) was 0.77 at 5 years. For the construction of immune cells prognosis model, 3 immune cells (T cells regulatory, Macrophages, Mast cells resting) were adopted, and the AUC was 0.65 at 5 years. We then merged the two models by correlation analysis and co-expression analysis. Finally, we found that KCNN4 positively correlates with T cells regulatory (Tregs) and negatively correlates with mast cells resting significantly. Furthermore, higher expression of KCNN4 may lead to a higher potential for immune evasion and lower efficiency for immune checkpoint inhibitors (ICIs).
conclusionsGenerally, this is the first study to assess the prognostic value of immune related ceRNA hub genes in ccRCC, and KCNN4 was finally demonstrated to be a key regulatory factor with strong correlation with Tregs and mast cells resting.
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