KIRCにおけるADRM1の癌促進および免疫抑制の役割の包括的解析と実験的確認

Kidney renal clear cell carcinoma (KIRC), as the major type of renal cell carcinoma, remains challenging due to its rapid malignant progression and poor prognosis. Adhesion-regulating molecule 1 (ADRM1) has been implicated in tumor development, yet its specific role in KIRC is poorly understood.

ADRM1 expression was analyzed using TCGA datasets and the CPTAC database. The differences in ADRM1 expression and its association with survival outcomes were investigated. The correlation of genetic alteration status with ADRM1 expression was studied. The effect of ADRM1 on immune infiltration was examined using R packages. Clinical samples were validated via qPCR and Western blot. In vitro functional assays assessed proliferation of KIRC cells. Transcriptional factors that regulated ADRM1 was confirmed by luciferase reporter gene assay. GSEA and experimental confirmation explored molecular pathways.

ADRM1 expression was significantly upregulated in KIRC, compared to normal tissues. The expression of ADRM1 was associated with high stages and poor prognosis of KIRC patients. The methylation level was positively associated with the expression of ADRM1 and indicated better survival outcomes. Overexpression of ADRM1 significantly promoted the proliferation of KIRC cells, while ADRM1 knockdown inhibited the proliferation of KIRC cells. ADRM1 expression was regulated by transcriptional factor CTCF. Moreover, ADRM1 promoted the proliferation of KIRC cells via ERK pathway. Immune analysis showed ADRM1 positively correlated with immune checkpoint genes (CTLA-4 and LAG3) and influenced Treg cells.

ADRM1 is transcriptionally regulated by CTCF and promotes KIRC proliferation through ERK pathway and has prognostic predictive value. It may become a novel therapeutic target for KIRC patients.