Abstract
BackgroundSuppressive tumor microenvironment is closely related to the progression and poor prognosis of lung adenocarcinoma (LUAD). Novel individual and universal immune-related biomarkers to predict the prognosis and immune landscape of LUAD patients are urgently needed. Two-gene pairing patterns could integrate and utilize various gene expression data.MethodsThe RNA-seq and relevant clinicopathological data of the LUAD project from the TCGA and well-known immune-related genes list from the ImmPort database were obtained. Co-expression analysis followed by an analysis of variance was performed to identify differentially expressed immune-related lncRNA (irlncRNA) (DEirlncRNA) between tumor and normal tissues. Two arbitrary DEirlncRNAs (DEirlncRNAs pair) in a tumor sample underwent pairwise comparison to generate a score (0 or 1). Next, Univariate analysis, Lasso regression and Multivariate analysis were used to screen survival-related DEirlncRNAs pairs and construct a prognostic model. The Acak information standard (AIC) values of the receiver operating characteristic (ROC) curve for 3 years are calculated to determine the cut-off point for high- or low-risk score. Finally, we evaluated the relationship between the risk score and overall survival, clinicopathological features, immune landscape, and chemotherapy efficacy.ResultsData of 54 normal and 497 tumor samples of LUAD were enrolled. After a strict screening process, 15 survival-independent-related DEirlncRNA pairs were integrated to construct a prognostic model. The AUC value of the 3-year ROC curve was 0.828. Kaplan–Meier analysis showed that patients with low risk lived longer than patients with high risk (p <0.001). Univariate and Multivariate Cox analysis suggested that the risk score was an independent factor of survival. The risk score was negatively associated with most tumor-infiltrating immune cells, immune score, and microenvironment scores. The low-risk group was correlated with increased expression of ICOS. The high-risk group had a connection with lower half inhibitory centration (IC50) of most chemotherapy drugs (e.g., etoposide, paclitaxel, vinorelbine, gemcitabine, and docetaxel) and targeted medicine—erlotinib, but with higher IC50 of methotrexate.ConclusionThe established irlncRNA pairs-based model is a promising prognostic signature for LUAD patients. Furthermore, the prognostic signature has great potential in the evaluation of tumor immune landscape and guiding individualized treatment regimens.
Highlights
Lung cancer remains the main cause of cancer death [1]
The prognosis for Lung adenocarcinoma (LUAD) is generally poor in virtue of the characteristics of early metastasis
We investigated the value of the prognostic model in evaluating the immune landscape and prediction of effects of chemotherapy and targeted therapy
Summary
Lung cancer remains the main cause of cancer death [1]. Lung adenocarcinoma (LUAD), as the most common pathological type of lung cancer, has brought great burden to the health care systems [2]. Chemotherapy and molecular targeted therapy are already conventional treatments for LUAD [3]. Suppressive tumor microenvironment is closely related to the progression and poor prognosis of lung cancer [4]. Immunotherapy targeted to relevant immunological mechanisms especially immune checkpoint inhibitor treatment has brought promising future for cure of LUAD patients [3, 5, 6]. It is necessary and theoretically feasible to find immune-related biomarkers that can predict the prognosis and treatment sensitivity of LUAD patients. Suppressive tumor microenvironment is closely related to the progression and poor prognosis of lung adenocarcinoma (LUAD). Novel individual and universal immune-related biomarkers to predict the prognosis and immune landscape of LUAD patients are urgently needed. Two-gene pairing patterns could integrate and utilize various gene expression data
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
