Wang Libo, Liu Zaoqu, Liu Long, Guo Chunguang, Jiao Dechao, Li Lifeng, Zhao Jie, Han Xinwei, Sun Yuling
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Institute of Hepatobiliary and Pancreatic Diseases, Zhengzhou University, Zhengzhou, China.
J Cell Mol Med. 2021 Aug;25(15):7559-7574. doi: 10.1111/jcmm.16791. Epub 2021 Jul 19.
CUGBP Elav-like family member 2(CELF2) plays crucial roles in the development and activation of T cell. However, the impacts of CELF2 on tumour-infiltrating immune cells (TIICs) and clinical outcomes of tumours remain unclear. In this study, we found that elevated CELF2 expression was markedly correlated with prolonged survival in multiple tumours, particularly in breast and lung cancers. Notably, CELF2 only impacted the prognosis of triple-negative breast cancer (TNBC) with lymph node metastasis. Further investigation showed CELF2 expression was positively correlated with the infiltration abundance of dendritic cells (DCs), CD8+ T cells and neutrophils in breast invasive carcinoma (BRCA) and DCs in lung squamous cell carcinoma (LUSC). CELF2 also had strong correlations with markers of diverse TIICs such as T cells, tumour-associated macrophages and DCs in BRCA and LUSC. Importantly, CELF2 was significantly associated with plenty of immune checkpoint molecules (ICMs) and outperformed five prevalent biomarkers including PD-1, PD-L1, CTLA-4, CD8 and tumour mutation burden in predicting immunotherapeutic responses. Immunohistochemistry also revealed lower protein levels of CELF2 in TNBC and LUSC compared to normal tissues, and patients with high expression showed significantly prolonged prognosis. In conclusion, we demonstrated that increased CELF2 expression was closely related to better prognosis and superior TIIC infiltration and ICM expression, particularly in BRCA and LUSC. CELF2 also performed well in evaluating the immunotherapeutic efficacy, suggesting CELF2 might be a promising biomarker.
CUGBP Elav样家族成员2(CELF2)在T细胞的发育和激活中发挥着关键作用。然而,CELF2对肿瘤浸润免疫细胞(TIICs)和肿瘤临床结局的影响仍不清楚。在本研究中,我们发现CELF2表达升高与多种肿瘤的生存期延长显著相关,尤其是在乳腺癌和肺癌中。值得注意的是,CELF2仅影响有淋巴结转移的三阴性乳腺癌(TNBC)的预后。进一步研究表明,CELF2表达与乳腺浸润性癌(BRCA)中的树突状细胞(DCs)、CD8 + T细胞和中性粒细胞以及肺鳞状细胞癌(LUSC)中的DCs的浸润丰度呈正相关。CELF2与BRCA和LUSC中多种TIICs的标志物如T细胞、肿瘤相关巨噬细胞和DCs也有很强的相关性。重要的是,CELF2与大量免疫检查点分子(ICMs)显著相关,并且在预测免疫治疗反应方面优于包括PD-1、PD-L1、CTLA-4、CD8和肿瘤突变负荷在内的五种常见生物标志物。免疫组织化学还显示,与正常组织相比,TNBC和LUSC中CELF2的蛋白水平较低,高表达患者的预后显著延长。总之,我们证明CELF2表达增加与更好的预后、优越的TIIC浸润和ICM表达密切相关,尤其是在BRCA和LUSC中。CELF2在评估免疫治疗疗效方面也表现良好,表明CELF2可能是一种有前途的生物标志物。