A Novel Prognostic Model of Early-Stage Lung Adenocarcinoma Integrating Methylation and Immune Biomarkers

Abstract

Lung adenocarcinoma (LUAD) is caused by multiple biological factors. Therefore, it will be more meaningful to study the prognosis from the perspective of omics integration. Given the significance of epigenetic modification and immunity in tumorigenesis and development, we tried to combine aberrant methylation and tumor infiltration CD8 T cell-related genes to build a prognostic model, to explore the key biomarkers of early-stage LUAD. On the basis of RNA-seq and methylation microarray data downloaded from The Cancer Genome Atlas (TCGA), differentially expressed genes and aberrant methylated genes were calculated with “DEseq2” and “ChAMP” packages, respectively. A Chi-square test was performed to obtain methylation driver genes. Weighted correlation network analysis (WGCNA) was utilized to mine cancer biomarkers related to CD8 T cells. With the consequences of univariate Cox proportional hazards analysis and least absolute shrinkage and selection operator (LASSO) COX regression analysis, the prognostic index based on 17 methylation driver genes (ZNF677, FAM83A, TRIM58, CLDN6, NKD1, NFE2L3, FKBP5, ITGA5, ASCL2, SLC24A4, WNT3A, TMEM171, PTPRH, ITPKB, ITGA2, SLC6A17, and CCDC81) and four CD8 T cell-related genes (SPDL1, E2F7, TK1, and TYMS) was successfully established, which could make valuable predictions for the survival risk of patients with early-stage LUAD.

The Fibrosis-Targeted Collagen/Integrins Gene Profile Predicts Risk of Metastasis in Pulmonary Neuroendocrine Neoplasms

“…Therefore, for all these reasons, we realize that COL1A2, COL3A1, COL5A2, ITGA5, ITGAV, and ITGB1 genes expression provide important predictive information about metastatic-free and overall survival in PNENs and our results now confirm the predictive importance of COL and ITG genes in PNENs. Whereas prior studies about lung cancer were able to show a significant relationship between COL5A2, ITGA5, ITGAV, and ITGB1 gene expression only in nonsmall cell lung cancer (54)(55)(56)(57)(58), our results suggest that COL5A2, ITGA5, and ITGB1 expression in PNENs, used as co-dependent variables, provide more information about the risk of metastasis and overall survival than does pathological stage. Moreover, the predictive value of COL5A2, ITGA5, and ITGB1 expression in PNENs persisted in the subset of patients with pathological stage I and II.…”

Signatures of Multi-Omics Reveal Distinct Tumor Immune Microenvironment Contributing to Immunotherapy in Lung Adenocarcinoma

“…A stable metabolism was required for T cell differentiation and effector function; metabolic deregulation could cause T cell dysfunction (47,48). FAM83A as MET signature shows a significant correlation to tumor mutation burden and DNA damage response pathways (49,50). DNA repair deficiency can trigger a more robust and long-lasting immune response, and strong TIL infiltration with tumor eradication with the presence of frameshift-mutated neoantigens, mutational landscape, and mismatch-repair deficiency are related to the immune response as candidate biomarkers for ICI immunotherapy (51,52).…”

Pan-cancer analysis combined with experiments explores the oncogenic role of spindle apparatus coiled-coil protein 1 (SPDL1)

“…Interestingly, the variant of SPDL1 reduce the incidence of different cancer types due to lower chromosomal alterations accumulated over time [ 20 ]. SPDL1 was identified as tumor infiltration CD8+ T cell-related genes in a prognostic model in LUAD, which indicate the potential relation of SPDL1 and immunity [ 21 ].…”