Screening and identifying a novel M-MDSCs-related gene signature for predicting prognostic risk and immunotherapeutic responses in patients with lung adenocarcinoma

Abstract

Background: Lung adenocarcinoma (LUAD) shows intratumoral heterogeneity, a highly complex phenomenon that known to be a challenge during cancer therapy. Considering the key role of monocytic myeloid-derived suppressor cells (M-MDSCs) in the tumor microenvironment (TME), we aimed to build a prognostic risk model using M-MDSCs-related genes.Methods: Monocytic myeloid-derived suppressor cells-related genes were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Utilized univariate survival analysis and random forest algorithm to screen candidate genes. A least absolute shrinkage and selection operator (LASSO) Cox regression analysis was selected to build the risk model. Patients were scored and classified into high- and low-risk groups based on the median risk scores. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis along with R packages “estimate” and “ssGSEA” were performed to reveal the mechanism of risk difference. Prognostic biomarkers and tumor mutation burden (TMB) were combined to predict the prognosis. Nomogram was carried out to predict the survival probability of patients in 1, 3, and 5 years.Results: 8 genes (VPREB3, TPBG, LRFN4, CD83, GIMAP6, PRMT8, WASF1, and F12) were identified as prognostic biomarkers. The GEO validation dataset demonstrated the risk model had good generalization effect. Significantly enrichment level of cell cycle-related pathway and lower content of CD8+ T cells infiltration in the high-risk group when compared to low-risk group. Morever, The patients were from the intersection of high-TMB and low-risk groups showed the best prognosis. The nomogram demonstrated good consistency with practical outcomes in predicting the survival rate over 1, 3, and 5 years.Conclusion: The risk model demonstrate good prognostic predictive ability. The patients from the intersection of low-risk and high-TMB groups are not only more sensitive response to but also more likely to benefit from immune-checkpoint-inhibitors (ICIs) treatment.

Breaking Barriers in Lung Cancer Research: The Intriguing Connection between IL-1β and PD-1/PD-L1 Pathways

“…Elevated serum IL-1β levels were correlated with decreased response to PD-L1 treatment and worsened survival outcomes, alluding to the potential role for serum IL-1β as a biomarker of response to combination therapies [3]. In another study, Wang et al noted the potential prognostic implication of tracking M-MDSCs-related genes (monocytic myeloid-derived suppressor cells) in the TME of lung adenocarcinoma (LUAD) [91]. Following the distinct genetic signatures of M-MDSCs-related genes may aid in our efforts to distinguish the effects of upregulated IL-1β and PD-1 expression in studying TME compositions that may have better responses to ICIs [91].…”

“…In another study, Wang et al noted the potential prognostic implication of tracking M-MDSCs-related genes (monocytic myeloid-derived suppressor cells) in the TME of lung adenocarcinoma (LUAD) [91]. Following the distinct genetic signatures of M-MDSCs-related genes may aid in our efforts to distinguish the effects of upregulated IL-1β and PD-1 expression in studying TME compositions that may have better responses to ICIs [91].…”

Comprehensive Review: Unveiling the Pro-Oncogenic Roles of IL-1ß and PD-1/PD-L1 in NSCLC Development and Targeting Their Pathways for Clinical Management

“…Elevated serum IL-1β levels were correlated with decreased response to PD-L1 treatment and worsened survival outcomes, alluding to the potential role for serum IL-1β as a biomarker of response to combination therapies [3]. In another study, Wang et al noted the potential prognostic implication of tracking M-MDSCs-related genes (monocytic myeloid-derived suppressor cells) in the TME of lung adenocarcinoma (LUAD) [92]. Following the distinct genetic signatures of M-MDSCs-related genes may aid in our efforts to distinguish the effects of upregulated IL-1β and PD-1 expression in studying TME compositions that may have better responses to ICIs [92].…”

“…In another study, Wang et al noted the potential prognostic implication of tracking M-MDSCs-related genes (monocytic myeloid-derived suppressor cells) in the TME of lung adenocarcinoma (LUAD) [92]. Following the distinct genetic signatures of M-MDSCs-related genes may aid in our efforts to distinguish the effects of upregulated IL-1β and PD-1 expression in studying TME compositions that may have better responses to ICIs [92].…”