A B7-CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in lung adenocarcinoma

作者：Zheng, Shanbo; Luo, Xiaoyang; Dong, Chuanpeng; Zheng, Difan; Xie, Juntao; Zhuge, Lingdun; Sun, Yihua^*; Chen, Haiquan^*

来源：International Journal of Cancer, 2018, 143(10): 2592-2601.

DOI：10.1002/ijc.31764

• B7
• CD28
• prognostic signature
• lung adenocarcinoma
• TCGA

B7 family ligands and CD28 family receptors have complicated interaction for modulating immune functions. They play a central role in response to immunotherapy and outcome of patients with lung adenocarcinoma (LUAD). Thus, we analyzed B7-CD28 family gene expression profiles in LUAD and generated a signature to predict prognosis and immune host status. B7-CD28 family gene expression profiles and clinical data of LUAD from The Cancer Genome Atlas (TCGA) were analyzed. In the training cohort, prognostic association was assessed and then a prognostic signature was built with stepwise multivariable Cox analysis. The signature was validated by Kaplan-Meier and multivariable Cox analysis in several published gene expression datasets and a Fudan University cohort. Expression of immune cell populations and other immunotherapy predictors was further investigated. In TCGA LUAD cohort, eight B7-CD28 family genes had prognostic association with p values <0.05. Stepwise regression generated a gene signature including two genes, CD28 and CD276. Signature high-risk cases had worse overall survival (OS) and disease-free survival (DFS) in three published gene expression datasets and a Fudan University validation cohort. The B7-CD28 family based signature also significantly stratified OS and DFS in important clinical subsets, including stage I-II and EGFR mutant subsets. Signature high- and low-risk tumor had significantly different expressions of PD-L1 and tumor infiltrating leukocytes. The B7-CD28 family based signature demonstrates significantly different prognoses and tumor immune landscapes in LUAD. Whether it could serve as potential biomarkers for immunotherapy needs further investigation. @@@ What's new? @@@ Changes in the expression of immune-modulating B7 ligands and CD28 receptors are associated with cancer. In particular, in lung adenocarcinoma, tumor-cell expression of B7 and CD28 is associated with patient outcome. This study links eight B7-CD28 family genes to lung adenocarcinoma prognosis. A B7-CD28 gene signature was developed and validated in independent cohorts and clinical subsets. The signature was associated with predictive immune markers for immunotherapy, including PD-L1 and tumor-infiltrating lymphocytes. The prognostic signature potentially could be used to facilitate patient counseling and to stratify lung adenocarcinoma patients who may benefit from personalized immune checkpoint therapy.

• 出版日期2018-11-15
• 单位复旦大学