Immune signature of T follicular helper cells predicts clinical prognostic and therapeutic impact in lung squamous cell carcinoma
Immune signature of T follicular helper cells predicts clinical prognostic and therapeutic impact in lung squamous cell carcinoma
复制标题
滤泡辅助 T 细胞的免疫特征可预测肺鳞状细胞癌的临床预后和治疗影响
DOI：
10.1016/j.intimp.2019.105932
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Chen, Yongsong
中科院分区：
文献类型：
--
作者：
Xu, Feng;Zhang, Hongpan;Chen, Yongsong
肺癌是全球男性和女性癌症相关死亡的主要原因。最近，肿瘤免疫异质性已被牵连在癌症的临床结果。然而，肺鳞状细胞癌（LUSC）中免疫细胞类型的预后意义尚不清楚，应进行系统研究。从基因表达Omnibus（GEO）数据库下载两个微阵列数据集（GSE 67061和GSE 2088），然后通过CIBERSORT算法整合以估计22种免疫细胞类型的分数。为了验证对LUSC的估计，还评估了LUSC TCGA的数据，以确定与通过考克斯回归分析确定的LUSC患者生存密切相关的特异性浸润免疫细胞类型。还评估了LUSC患者之间的免疫和化疗反应。通过考克斯回归分析获得T滤泡辅助细胞以开发预后标志。根据该免疫预后风险评分，T滤泡辅助细胞的免疫特征是预测LUSC患者总生存期的独立和特异性预后特征。此外，高危组中N6-甲基腺苷（m（6）A）RNA甲基化调节因子ALKBH 5、胃L3、HNRNPC和KIAA 1429的表达较低，对免疫治疗和化疗的敏感性更高。这项研究表明，这种免疫特征是LUSC预后的重要决定因素，并可能为免疫和化疗开发提供潜在的预后生物标志物或治疗靶点。
Lung cancer is the leading reason of cancer-related death from cancer globally for both men and women. Recently, tumor immune heterogeneity has been implicated in cancer clinical outcome. However, this prognostic significance of immune cell types in lung squamous cell carcinoma (LUSC) is unclear and should be systematically investigated. Two microarray datasets (GSE67061 and GSE2088) from the Gene Expression Omnibus (GEO) database were downloaded and then integrated to estimate the fraction of 22 immune cell types by CIBERSORT algorithm. To validate the estimation for LUSC, the data of LUSC TCGA were also assessed in order to determine specific infiltrating immune cell type closely correlated with LUSC patients' survival determined by Cox regression analyses. Immunotherapeutic and chemotherapeutic response between the LUSC patients were also evaluated. T follicular helper cells were obtained by Cox regression analysis to develop the prognostic signature. According to this immune prognostic risk score, immune signature of T follicular helper cells is an independent and specific prognostic signature for predictions of LUSC patient overall survival. Moreover, high-risk group exhibited less expression of N6-methyladenosine (m(6)A) RNA methylation regulator including ALKBH5, METTL3, HNRNPC and KIAA1429 and was much more sensitive to immunotherapy and chemotherapy. This study suggests that this immune signature is important determinants of prognosis in LUSC and may provide potential prognostic biomarker or therapeutic target for immunotherapeutic and chemotherapeutic development.