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CELF2 is a candidate prognostic and immunotherapy biomarker in triple‐negative breast cancer and lung squamous cell carcinoma: A pan‐cancer analysis

机译:Celf2是三阴性乳腺癌和肺鳞癌中的候选预后和免疫疗法生物标志物:泛癌分析

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摘要

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.
机译:Cugbp般的家庭成员2(Celf2)在T细胞的开发和激活中起着至关重要的作用。然而,Celf2对肿瘤浸润的免疫细胞(Tiics)和肿瘤临床结果的影响仍不清楚。在这项研究中,我们发现升高的Celf2表达与多种肿瘤的延长存活率明显相关,特别是在乳腺癌和肺癌中。值得注意的是,Celf2只影响了三阴性乳腺癌(TNBC)的预后,淋巴结转移。进一步的研究表明,CELF2表达与乳乳癌(BRCA)和DC在肺鳞状细胞癌(LUSC)中的树突状细胞(DCS),CD8 + T细胞和中性粒细胞的浸润丰度正相关。 Celf2还与不同Tiics的标记等具有强烈的相关性,例如T细胞,BRCA和LUSC中的T细胞,肿瘤相关的巨噬细胞和DC。重要的是,CELF2与大量免疫检查点分子(ICMS)显着相关,并且优于预测免疫治疗反应的PD-1,PD-L1,CTLA-4,CD8和肿瘤突变负担的优于五种普遍的生物标志物。免疫组织化学还揭示了TNBC和LUSC中Celf2的蛋白质水平,与正常组织相比,高表达患者显着延长了预后显着延长。总之,我们证明,增加的Celf2表达与更好的预后和优越的TIIC浸润和ICM表达密切相关,特别是在BRCA和LUSC中。 Celf2也在评估免疫治疗疗效时表现良好,暗示Celf2可能是一个有前途的生物标志物。

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