Abstract
Inflammation is an important hallmark of cancer and plays a role in both neogenesis and tumor development. Despite this, inflammatory-related genes (IRGs) remain to be poorly studied in lung adenocarcinoma (LUAD). We aim to explore the prognostic value of IRGs for LUAD and construct an IRG-based prognosis signature. The transcriptomic profiles and clinicopathological information of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Least absolute shrinkage and selection operator (LASSO) analysis and multivariate Cox regression were applied in the TCGA set to generate an IRG risk signature. LUAD cases with from the GSE31210 and GSE30219 datasets were used to validate the predictive ability of the signature. Analysis of the TCGA cohort revealed a five-IRG risk signature consisting of EREG, GPC3, IL7R, LAMP3, and NMUR1. This signature was used to divide patients into two risk groups with different survival rates. Multivariate Cox regression analysis verified that the risk score from the five-IRG signature negatively correlated with patient outcome. A nomogram was developed using the IRG risk signature and stage, with C-index values of 0.687 (95% CI: 0.644–0.730) in the TCGA training cohort, 0.678 (95% CI: 0.586–0.771) in GSE30219 cohort, and 0.656 (95% CI: 0.571–0.740) in GSE30219 cohort. Calibration curves were consistent between the actual and the predicted overall survival. The immune infiltration analysis in the TCGA training cohort and two GEO validation cohorts showed a distinctly differentiated immune cell infiltration landscape between the two risk groups. The IRG risk signature for LUAD can be used to predict patient prognosis and guide individual treatment. This risk signature is also a potential biomarker of immunotherapy.
Highlights
Lung cancer is the second most common malignancy and has the highest mortality rate (Sung et al, 2021)
After differential expression analysis in the The Cancer Genome Atlas (TCGA) dataset between 535 tumor tissues and 59 normal tissues, we discovered 2,849 upregulated and 689 downregulated Differentially expressed genes (DEGs), including 22 differentially expressed inflammatory-related genes (IRGs)
A five-IRG risk signature was constructed according to the 488 lung adenocarcinoma (LUAD) cases in the TCGA cohort, whose risk scores were calculated based on a linear combination of gene expression levels and their corresponding regression coefficients
Summary
Lung cancer is the second most common malignancy and has the highest mortality rate (Sung et al, 2021). Inflammation is the immune system’s response to infection, trauma, and other stresses (Gomes et al, 2014). It is important in cancer, where it plays multiple roles (Hanahan and Weinberg, 2011). The local inflammatory response promotes the occurrence and development of tumors by releasing important molecules and carcinogens to the tumor microenvironment. These can include survival factors that limit apoptosis, growth factors that sustain the proliferative signaling, and pro-angiogenic factors (Ben-Baruch, 2006; Hanahan and Weinberg, 2011). The lymphocyte-to-monocyte ratio and the neutrophil-tolymphocyte ratio, which are indicators of the systemic inflammatory response, and have been found to be prognostic factors in patients with LUAD (Takahashi et al, 2016; Minami et al, 2018)
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.
