Establishment and validation of an immune-associated signature in lung adenocarcinoma.

Recent studies demonstrated that immune associated genes (IAGs) played an important role in the treatment of lung adenocarcinoma (LUAD). In the research, we established an IAGs signature and validated its prognostic value in LUAD by using bioinformatic methods and public databases. Based on the RNA-Seq samples from The Cancer Genome Atlas (TCGA), 576 differentially expressed IAGs were firstly identified. The R package coxph was used to select significant prognostic IAGs using both univariate and multivariate analyses. As a result, four IAGs (SCG2, CCL20, CAT, S100P) were finally screened in an IAGs signature. Based on these four IAGs, LASSO (least absolute shrinkage and selection operator) Cox regression analysis was used to construct a Risk score prognostic model and survival analysis revealed that high risk score was significantly associated with poor survival outcomes, which was validated in the external datasets GSE68465 and GSE31210. In addition, Risk score was found to be significantly associated with stage, lymphatic involvement, tumor metastasis and immune cells (B cells and dendritic cells) infiltration. Moreover, it was found that TP53 and EGFR had a higher mutation frequency in high risk group. Then a nomogram with clinical characteristics was established to superiorly predict prognosis of LUAD patients, and calibration plots and ROC analysis proved its accuracy. We believe that our findings can be conveniently used for individualized prediction of the clinical prognosis for LUAD patients, but further clinical trials and experimental exploration are needed to validate our observations.

Wang Z ，Chen X 《-》

Immune landscape and a promising immune prognostic model associated with TP53 in early-stage lung adenocarcinoma.

TP53 mutation, one of the most frequent mutations in early-stage lung adenocarcinoma (LUAD), triggers a series of alterations in the immune landscape, progression, and clinical outcome of early-stage LUAD. Our study was designed to unravel the effects of TP53 mutation on the immunophenotype of early-stage LUAD and formulate a TP53-associated immune prognostic model (IPM) that can estimate prognosis in early-stage LUAD patients. Immune-associated differentially expressed genes (DEGs) between TP53 mutated (TP53MUT ) and TP53 wild-type (TP53WT ) early-stage LUAD were comprehensively analyzed. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis identified the prognostic immune-associated DEGs. We constructed and validated an IPM based on the TCGA and a meta-GEO composed of GSE72094, GSE42127, and GSE31210, respectively. The CIBERSORT algorithm was analyzed for assessing the percentage of immune cell types. A nomogram model was established for clinical application. TP53 mutation occurred in approximately 50.00% of LUAD patients, stimulating a weakened immune response in early-stage LUAD. Sixty-seven immune-associated DEGs were determined between TP53WT and TP53MUT cohort. An IPM consisting of two prognostic immune-associated DEGs (risk score = 0.098 * ENTPD2 expression + 0.168 * MIF expression) was developed through 397 cases in the TCGA and further validated based on 623 patients in a meta-GEO. The IPM stratified patients into low or high risk of undesirable survival and was identified as an independent prognostic indicator in multivariate analysis (HR = 2.09, 95% CI: 1.43-3.06, p < 0.001). Increased expressions of PD-L1, CTLA-4, and TIGIT were revealed in the high-risk group. Prognostic nomogram incorporating the IPM and other clinicopathological parameters (TNM stage and age) achieved optimal predictive accuracy and clinical utility. The IPM based on TP53 status is a reliable and robust immune signature to identify early-stage LUAD patients with high risk of unfavorable survival.

Wu C ，Rao X ，Lin W 《Cancer Medicine》

A Seven-Gene Signature with Close Immune Correlation Was Identified for Survival Prediction of Lung Adenocarcinoma.

Zou X ，Hu Z ，Huang C ，Chang J ... -  《MEDICAL SCIENCE MONITOR》

Identification of a methylomics-associated nomogram for predicting overall survival of stage I-II lung adenocarcinoma.

Wang H ，Wei C ，Pan P ，Yuan F ，Cheng J ... -  《Scientific Reports》

Combination of tumor mutation burden and immune infiltrates for the prognosis of lung adenocarcinoma.

Tumor mutation burden (TMB) levels are associated with immune infiltrates in the tumor microenvironment and can modulate the responses to immune checkpoint inhibitors (ICIs) in lung adenocarcinoma (LUAD) patients. This study aimed at exploring the potential role of a signature of genes associated with TMB and immune infiltrates and the relevant nomogram in the prognosis of LUAD. The TMB levels in LUAD patients in the Cancer Genome Atlas (TCGA) were analyzed. The differentially expressed genes (DEGs) between the higher- and lower-TMB subgroups were functionally analyzed. The immune-related DEGs and their relationship with immune infiltrates in the tumor environment between two subgroups were analyzed. Nine immune-related DEGs were used to generate a TMB-related immune signature. The sensitivity to immunotherapy in TCGA-LUAD patients was analyzed by immunophenotypic scores (IPS). Subsequently, a nomogram was generated using tumor-related parameters and the signature score. The signature or nomogram values in predicting overall survival (OS) were evaluated and validated in LUAD patients in the GSE30219 and GSE72094. There were 468 DEGs between the higher and lower-TMB subgroups of LUAD patients. The TMB levels were associated positively with the number of immune infiltrates in LUAD patients. Nine DEGs were related to immune infiltrates in the tumor environment. The higher signature scores (high-risk) were associated with poor prognosis of LUAD in the TCGA, which was validated in LUAD patients of the GSE30219 and GSE72094 datasets. Interestingly, the patients in the high-risk group had higher PD-L1 expression in their tumors and the risk scores in LUAD patients. The IPS of LUAD patients in the high-risk group were predicted to benefit from immunotherapy. Finally, the nomogram had high AUC values in predicting the OS of LUAD patients. The TMB-related immune signature or nomogram is valuable for the prognosis of LUAD patients and evaluating their responses to ICIs. These relevant genes may participate into the pathogenesis, ICIs, and drug resistance of LUAD.

Zhao Z ，He B ，Cai Q ，Zhang P ，Peng X ，Zhang Y ，Xie H ，Wang X ... -  《-》