Abstract
Background: Inflammatory responses are strongly linked with tumorigenesis and cancer development. This research aimed to construct and validate a novel inflammation response–related risk predictive signature for forecasting the prognosis of patients with LUAD. Methods: Differential expression analysis, univariate Cox, LASSO, and multivariate Cox regression analyses of 200 inflammatory response–related genes (IRRG) were performed to establish a risk predictive model in the TCGA training cohort. The performance of the IRRG model was verified in eight GEO datasets. GSEA analysis, ESTIMATE algorithms, and ssGSEA analysis were applied to elucidate the possible mechanisms. Furthermore, the relationship analysis between risk score, model genes, and chemosensitivity was performed. Last, we verified the protein expression of seven model genes by immunohistochemical staining or Western blotting. Results: We constructed a novel inflammatory response–related 7-gene signature (MMP14, BTG2, LAMP3, CCL20, TLR2, IL7R, and PCDH7). Patients in the high-risk group presented markedly decreased survival time in the TCGA cohort and eight GEO cohorts than the low-risk group. Interestingly, multiple pathways related to immune response were suppressed in high-risk groups. The low infiltration levels of B cell, dendritic cell, natural killer cell, and eosinophil can significantly affect the unsatisfactory prognosis of the high-risk group in LUAD. Moreover, the tumor cells’ sensitivity to anticancer drugs was markedly related to risk scores and model genes. The protein expression of seven model genes was consistent with the mRNA expression. Conclusion: Our IRRG prognostic model can effectively forecast LUAD prognosis and is tightly related to immune infiltration.
Highlights
Lung cancer is a clinical malignancy with the third highest morbidity and the highest mortality worldwide (Siegel et al, 2021)
Microarray data of lung adenocarcinoma (LUAD) were downloaded from the Gene Expression Omnibus (GEO) dataset. 200 inflammatory response–related genes (IRRG) were downloaded from the MSigDB platform (Supplementary Table S1)
We revealed that the inflammatory response pathway is suppressed in LUAD from The Cancer Genome Atlas (TCGA) (Figure 1A) which was verified in five GEO datasets (Figures 1B–F)
Summary
Lung cancer is a clinical malignancy with the third highest morbidity and the highest mortality worldwide (Siegel et al, 2021). With the progress of RNA sequencing technology, an increasing number of key genes have been discovered, and their abnormal expression can drive cancer initiation and development and predict the patient’s prognosis. As we all know, tumors are highly polygenic, and a single gene cannot well forecast the prognosis of tumor patients (Zhang et al, 2020). There is an urgent need for a more effective prognostic model integrated with multiple genes for prognosis prediction and potential therapeutic targets in patients with LUAD. Inflammatory responses are strongly linked with tumorigenesis and cancer development.
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