Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Anticancer Res. 2023 Aug;43(8):3493-3506. doi: 10.21873/anticanres.16526.
BACKGROUND/AIM: CD44 is a critical cell-surface glycoprotein. However, its prognostic significance and correlation with tumor-infiltrating lymphocytes in clear cell renal cell carcinoma (ccRCC) are not well-understood.
The mRNA and protein levels of CD44 in ccRCC were assessed. The prognostic value of CD44 was analyzed in the TCGA and PrognoScan databases. The functional enrichment and immune infiltrates analyses were conducted. The STRING database was used to analyze the protein interactions of CD44. Tissue array, western blot, qRT-PCR, and transwell assay were performed to determine the expression and biological function of CD44 in ccRCC cells.
CD44 was highly expressed in ccRCC and correlated with poor prognosis. CD44 mRNA and protein expression was associated with TNM stage, pathologic stage, and histologic grade. Functional enrichment analyses revealed CD44 is involved in extracellular matrix organization, metastasis, IL6/JAK/STAT3 signaling and so on. Moreover, CD44 expression was positively correlated with infiltrating levels of macrophages, Th2 cells and Th1 cells in ccRCC. Combining the immune infiltration analysis and immunohistochemistry, the SPP1/CD44 axis might participate in immune escape through regulating PD-L2 expression. Experiments indicated that CD44 was increased in ccRCC and inhibition of CD44 could suppress the migration of ccRCC cells.
High expression of CD44 in ccRCC was associated with metastasis, poor prognosis, and high infiltrating levels of macrophages. The SPP1/CD44 axis potentially contributes to the regulation of PD-L2. These results demonstrated that targeting the SPP1/CD44 axis or inhibiting CD44 expression may be a new therapy to suppress ccRCC progression.
背景/目的：CD44 是一种重要的细胞表面糖蛋白。然而，其在透明细胞肾细胞癌（ccRCC）中的预后意义及其与肿瘤浸润淋巴细胞的相关性尚不清楚。
评估 ccRCC 中 CD44 的 mRNA 和蛋白水平。在 TCGA 和 PrognoScan 数据库中分析 CD44 的预后价值。进行功能富集和免疫浸润分析。使用 STRING 数据库分析 CD44 的蛋白相互作用。通过组织阵列、western blot、qRT-PCR 和 Transwell 测定来确定 CD44 在 ccRCC 细胞中的表达和生物学功能。
CD44 在 ccRCC 中高表达，并与不良预后相关。CD44 mRNA 和蛋白表达与 TNM 分期、病理分期和组织学分级相关。功能富集分析表明，CD44 参与细胞外基质组织、转移、IL6/JAK/STAT3 信号等过程。此外，CD44 表达与 ccRCC 中巨噬细胞、Th2 细胞和 Th1 细胞的浸润水平呈正相关。结合免疫浸润分析和免疫组化，SPP1/CD44 轴可能通过调节 PD-L2 表达参与免疫逃避。实验表明，ccRCC 中 CD44 表达增加，抑制 CD44 可抑制 ccRCC 细胞的迁移。
ccRCC 中 CD44 的高表达与转移、不良预后和巨噬细胞的高浸润水平相关。SPP1/CD44 轴可能有助于 PD-L2 的调节。这些结果表明，靶向 SPP1/CD44 轴或抑制 CD44 表达可能是抑制 ccRCC 进展的新疗法。
