<br>CENPF 作为与皮肤黑色素瘤中 CD4+ 记忆 T 细胞相对应的独立预后和转移生物标志物,Cancer Science

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CENPF 作为与皮肤黑色素瘤中 CD4+ 记忆 T 细胞相对应的独立预后和转移生物标志物
Cancer Science ( IF 4.5 ) Pub Date : 2022-02-21 , DOI: 10.1111/cas.15303
Mengzhi Li ₁ , Jingling Zhao ₁ , Ronghua Yang ₂ , Ruizhao Cai ₁ , Xusheng Liu ₁ , Julin Xie ₁ , Bin Shu ₁ , Shaohai Qi ₁

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由于免疫疗法的最新进展，皮肤黑色素瘤（SKCM）患者的总生存率有所增加；然而，转移患者的5年生存率仍然很低。通过分析差异表达基因（GSE3189和GSE46517）筛选皮肤黑色素瘤上调基因，并通过GSE46517数据集的加权基因共表达网络分析鉴定转移相关癌基因。经肿瘤免疫评估资源证实，我们在 SKCM 及其转移瘤中发现高表达的着丝粒蛋白 F (CENPF)。人类黑色素瘤组织的免疫染色显示 CENPF 高表达。根据Kaplan-Meier生存曲线对数秩检验、接受者操作特征曲线以及单变量和多变量分析，癌症基因组图谱（TCGA）数据库表明CENPF是SKCM的典型独立预测因子。 CIBERSORT 算法对 GSE46517 的免疫细胞类型进行了分类，结果显示转移性黑色素瘤中 CD4+ 记忆激活 T 细胞的比例较高。 TCGA 数据的单样本基因集富集分析证实了 CENPF 与激活的 CD4+ T 细胞之间的相关性。通过相关分析，着丝粒蛋白 F 与肿瘤突变负荷和 CD4+ 记忆 T 细胞标志物（白细胞介素 [IL]-23A、CD28 和 CD62L）呈正相关，与记忆 T 细胞维持因子（IL-7 和 IL-15）呈负相关。此外，免疫荧光显示黑色素瘤中 CENPF 与 IL23A、CD4 高度共表达。 CENPF 上调可能导致 CD4+ 记忆 T 细胞过早耗竭和免疫抑制。列线图表明 CENPF 对 1 年、3 年、5 年和 7 年黑色素瘤总生存率的临床预测价值。因此，CENPF在黑色素瘤的进展和转移中起着至关重要的作用，可以成为有效的治疗靶点。

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CENPF as an independent prognostic and metastasis biomarker corresponding to CD4+ memory T cells in cutaneous melanoma

Owing to recent advances in immunotherapies, the overall survival of patients with skin cutaneous melanoma (SKCM) has increased; however, the 5-year survival rate of metastatic patients remains poor. Skin cutaneous melanoma—upregulated genes were screened via analysis of differentially expressed genes (GSE3189 and GSE46517), and metastasis-related oncogenes were identified via weighted gene coexpression network analysis of the GSE46517 dataset. As confirmed by the Tumor Immune Estimation Resource, we found highly expressed centromere protein F (CENPF) in SKCM and its metastases. Immunostaining of human melanoma tissues demonstrated high CENPF expression. According to the Kaplan-Meier survival curve log-rank test, receiver-operating characteristic curve, and univariate and multivariate analyses, the Cancer Genome Atlas (TCGA) database suggested CENPF be a typical independent predictor of SKCM. The CIBERSORT algorithm classified the types of the immune cells from GSE46517 and showed higher proportion of CD4+ memory-activated T cells in metastatic melanoma. Single-sample gene set enrichment analysis of TCGA data confirmed the correlation between CENPF and activated CD4+ T cells. Centromere protein F was positively correlated with tumor mutational burden and CD4+ memory T cell markers (interleukin [IL]-23A, CD28, and CD62L), negatively associated with memory T cell maintenance factors (IL-7 and IL-15) by correlation analysis. Moreover, immunofluorescence showed high coexpression of CENPF and IL23A, CD4 in melanoma. Upregulated CENPF might lead to premature depletion of CD4+ memory T cells and immunosuppression. Nomogram indicated CENPF clinical predictive value for 1-, 3-, 5-, and 7-year melanoma overall survival. Therefore, CENPF plays a vital role in the progression and metastasis of melanoma and can be an effective therapeutic target.

更新日期：2022-02-21

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