As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner

Abstract

Background Clear cell renal cell carcinoma (ccRCC) is one of the most lethal malignancies in the urinary system and the existing immunotherapy has not achieved satisfactory outcomes. Therefore, this study aims at establishing a novel gene signature for immune infiltration and clinical outcome (overall survival and immunotherapy responsiveness) in ccRCC patients. Methods Based on RNA sequencing data and clinical information in The Cancer Genome Atlas (TCGA) database, we calculated proportions of immune cells in 611 samples using an online tool CIBERSORTx. Multivariate survival analysis was conducted to determine crucial survival-associated immune cells and immune-infiltration-related genes (IIRGs). Next, the clinical specimens and common renal cancer cell lines were applied to confirm IIRGs expression at protein and RNA levels. Finally, functional enrichment analyses and siRNA technology targeted to RUFY4 were implemented to verify its function of predicting immunotherapy response. Results Follicular helper T cells (TFHs) and Regulatory T cells (Tregs) were highly infiltrated in the tumor microenvironment (TME) and their relative proportions were independent prognostic factors for patients. Among IIRGs of TFHs and TREGs, RUFY4 was found to be highly activated in tumor microenvironment and its co-expression network was enriched in PDL1/PD1 checkpoint pathway in cancer. Additionally, knockdown of RUFY4 led to the decline of PDL1 and proliferation ability in ccRCC cell lines. Conclusion TFHs and Tregs were considered as prognostic biomarkers and RUFY4 was an immunotherapeutic predictor of ccRCC patients in a PDL1-Related manner.

Identification of a risk score model based on tertiary lymphoid structure‐related genes for predicting immunotherapy efficacy in non‐small cell lung cancer

“…The risk score model included five genes (RGS8, RUFY4, HLA‐DQB2, THEMIS, and TRBV12‐5), and the role of RGS8 has previously been found to be controversial in solid cancers for its positive prognosis effect on thyroid carcinoma and negative prognosis effect on ovarian cancer, 43,44 while we found RGS8 high expression was associated with poor prognosis. Miao et al indicated that the depletion of RUFY4 led to the decrease of PD‐L1, speculating that RUFY4 regulated the expression level of PD‐L1 by involving in JAK–STAT and/or NF‐kappa B signaling pathways, there by influencing immunotherapy responsiveness 45 . Being a member of the MHC class II family, HLA‐DQB2 is an important molecule involved in the T cell immune response and antigen presentation.…”

HSD3B7 as a prognostic-related biomarker predicts poor prognostic in ccRCC

“…Moreover, Carril ajuria l et al found that the SWI/SNF chromatin remodelling complex gene PBRM1 is also one of the key genes of ccRCC [26,27]. Recent studies have found that OIP5[28], RUFY4 [29] and MUC20 [30] are related to the immune microenvironment (TME) of ccRCC and may be used as new therapeutic targets. However, these are not enough to understand the development and prognosis of ccRCC.…”

N6‐methyladenosine‐modified DBT alleviates lipid accumulation and inhibits tumor progression in clear cell renal cell carcinoma through the ANXA2/YAP axis‐regulated Hippo pathway

“…The procedure was carried out as previously described [ 30 ]. Cells were starved for 24 h. The top chamber of the Transwell plate (#REF3422, Corning Inc., Corning, NY, USA) was coated by the Matrigel (#356234, dilution 1:8, Corning Inc.).…”