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

Abstract

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.

An immune infiltration signature to predict the overall survival of patients with colon cancer

“…To date, however, this viewpoint has not been well‐translated into clinical implications and significance. In addition, a number of existing studies have focused on the role of immune gene signatures, rather than of immune cells composition, in the initiation and progression of cancer . In the present study, we first constructed a PIS model for predicting the overall survival of patients based on the fractions of 17 immune cell types using LASSO penalized regression.…”

Identification of a costimulatory molecule-based signature for predicting prognosis risk and immunotherapy response in patients with lung adenocarcinoma

“…Before our study, a signature based on the expression of costimulatory molecules from the B7-CD28 family was constructed. 31 Through meta-analysis, we obtained two crucial conclusions: the CMS signature had prognostic significance across these public datasets, although some of the P-values were not statistically significant and our CMS model demonstrated an advantage over the reported B7-CD28 model. These conclusions are consistent with our finding that the TNF family has a more important prognostic value for patients with LUAD.…”

“…Prior to the creation of our signature, Shanbo Zheng et al constructed a signature for LUAD based on the costimulatory molecules from the B7-CD28 family (B7-CD28 signature) with a risk score of 0.3313× CD276 -0.1559× CD28. 31 We then comprehensively assessed the prognostic significance of our CMS and the B7-CD28 signature by examining public datasets and conducting prognostic meta-analyses based on the nine groups (n = 1472) of the two different signature groups. As shown in Figure 3(a), our CMS performed very well in the different cohorts, producing HRs larger than 1.…”

Identification of a costimulatory molecule-based signature for predicting prognosis risk and immunotherapy response in patients with lung adenocarcinoma

“…Prior to the creation of our signature, Shanbo Zheng et al constructed a signature for LUAD based on the costimulatory molecules from the B7-CD28 family (B7-CD28 signature) with a risk score of 0.3313 × CD276-0.1559 × CD28. [31] We then comprehensively assessed the prognostic significance of our CMS and the B7-CD28 signature by examining public datasets and conducting prognostic metaanalyses based on the nine groups (n = 1472) of the two different signature groups. As shown in Fig.…”