Predictive value of dendritic cell-related genes for prognosis and immunotherapy response in lung adenocarcinoma

Patients with lung adenocarcinoma (LUAD) receiving drug treatment often have an unpredictive response and there is a lack of effective methods to predict treatment outcome for patients. Dendritic cells (DCs) play a significant role in the tumor microenvironment and the DCs-related gene signature may be used to predict treatment outcome. Here, we screened for DC-related genes to construct a prognostic signature to predict prognosis and response to immunotherapy in LUAD patients.

DC-related biological functions and genes were identified using single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing. DCs-related gene signature (DCRGS) was constructed using integrated machine learning algorithms. Expression of key genes in clinical samples was examined by real-time q-PCR. Performance of the prognostic model, DCRGS, for the prognostic evaluation, was assessed using a multiple time-dependent receiver operating characteristic (ROC) curve, the R package, "timeROC", and validated using GEO datasets.

Analysis of scRNA-seq data showed that there is a significant upregulation of LGALS9 expression in DCs isolated from malignant pleural effusion samples. Leveraging the Coxboost and random survival forest combination algorithm, we filtered out six DC-related genes on which a prognostic prediction model, DCRGS, was established. A high predictive capability nomogram was constructed by combining DCRGS with clinical features. We found that patients with a high-DCRGS score had immunosuppression, activated tumor-associated pathways, and elevated somatic mutational load and copy number variant load. In contrast, patients in the low-DCRGS subgroup were resistant to chemotherapy but sensitive to the CTLA-4 immune checkpoint inhibitor and targeted therapy.

We have innovatively established a deep learning-based prediction model, DCRGS, for the prediction of the prognosis of patients with LUAD. The model possesses a strong prognostic prediction performance with high accuracy and sensitivity and could be clinically useful to guide the management of LUAD. Furthermore, the findings of this study could provide an important reference for individualized clinical treatment and prognostic prediction of patients with LUAD.