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The role of CD28 in the prognosis of young lung adenocarcinoma patients.

ABSTRACT: BACKGROUND:The prognosis of lung cancer was found to be associated with a series of biomarkers related to the tumor immune microenvironment (TIME), which can modulate the biological behaviors and consequent outcomes of lung cancer. Therefore, establishing a prognostic model based on the TIME for lung cancer patients, especially young patients with lung adenocarcinoma (LUAD), is urgently needed. METHODS:In all, 809 lung cancer patients from the TCGA database and 71 young patients with LUAD in our center were involved in this study. Univariate and multivariate analysis based on clinical characteristics and TIME-related expression patterns (as evaluated by IHC) were performed to estimate prognosis and were verified by prognostic nomograms. RESULTS:Both LUAD and lung cancer patients with high CD28 expression had shorter disease-free survival (DFS) (P?=?0.0011; P?=?0.0001) but longer overall survival (OS) (P?=?0.0001; P?=?0.0282). TIME-related molecules combined with clinical information and genomic signatures could predict the prognosis of young patients with LUAD with robust efficiency and could be verified by the established nomogram based on the Cox regression model. In addition, CD28 expression was correlated with an abundance of lymphocytes and could modulate the TIME. Higher CD28 levels were observed in primary tumors than in metastatic tissues. CONCLUSION:TIME-related molecules were identified as compelling biomarkers for predicting the prognosis of lung cancer, especially in a cohort of young patients. Furthermore, CD28, which is associated with poor DFS but long OS, might participate in the modulation of the TIME and has a different role in the prognosis of young patients with LUAD.

SUBMITTER: Sun D

PROVIDER: S-EPMC7510131 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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The role of CD28 in the prognosis of young lung adenocarcinoma patients.

Sun Dantong D Tian Lu L Bian Tiantian T Zhao Han H Tao Junyan J Feng Lizong L Liu Qiaoling Q Hou Helei H

BMC cancer 20200923 1

<h4>Background</h4>The prognosis of lung cancer was found to be associated with a series of biomarkers related to the tumor immune microenvironment (TIME), which can modulate the biological behaviors and consequent outcomes of lung cancer. Therefore, establishing a prognostic model based on the TIME for lung cancer patients, especially young patients with lung adenocarcinoma (LUAD), is urgently needed.<h4>Methods</h4>In all, 809 lung cancer patients from the TCGA database and 71 young patients w ...[more]

PMID: 32967633

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Project description:Background:Immune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients. Methods:We first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database. Results:Among the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway. Conclusions:Our findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy.

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The role of CD28 in the prognosis of young lung adenocarcinoma patients.

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The role of CD28 in the prognosis of young lung adenocarcinoma patients.

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