Caspase recruiting domain-containing protein 11 (CARD11) serves as a therapeutic biomarker for the drug therapies of clear cell renal cell carcinoma

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Abstract Clear cell renal cell carcinoma (ccRCC) belongs to the ten most diagnosed cancer types worldwide. Novel drug therapies are introduced and beneficial to the advanced ccRCC but lack effective biomarkers for the therapeutic response. Tumor-infiltrating immune cells and gene signatures are two critical factors for the response to immunotherapy and targeted therapy. Meanwhile, Caspase recruiting domain-containing protein 11 (CARD11) owns a deep connection with the immune system and has recently been identified to play a role in tumor development. Therefore, we investigated the CARD11 expression and its association with the immune environment in ccRCC to discover novel therapeutic biomarkers. Data from TCGA and GEO together with IHC were extracted to analyze the mRNA and protein expression of CARD11 in ccRCC. EWAS Atlas and cBioPortal provided the epigenomic modification information of CARD11. Then, we utilized the ESTIMATE, ssGSEA, and TIP to illustrate the relationship between CARD11 expression and the immune landscape in ccRCC. Furthermore, CARD11 was investigated for its correlation with the response toward immunotherapy and targeted therapy through the online datasets TIDE and GDSC. As we found, CARD11 expression was upregulated which may be mainly modified by body methylation and was correlated with poor prognosis in ccRCC. In the tumor microenvironment of ccRCC, CARD11 expression was positively correlated with increased T lymphocyte infiltration and increased expression of inhibitory immune checkpoints. Moreover, ccRCC patients with high CARD11 expression had a better response to immunotherapy and targeted therapy. The knockdown of CARD11 ultimately suppressed the proliferation, migration, and invasion capabilities of ccRCC cells while simultaneously enhancing tumor cell apoptosis. In summary, we identified CARD11 as a novel therapeutic biomarker for immunotherapy and targeted therapy in ccRCC.

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