Risk stratification for lung adenocarcinoma on EGFR and TP53 mutation status, chemotherapy, and PD‐L1 immunotherapy

Abstract

The overall survival rates for lung cancer remain unsatisfactorily low, even for patients with biomarkers for which target therapies or immunotherapies are recommended. Better identification of at‐risk patients is needed to achieve more effective personalized treatment. Here, we derived a risk‐stratifying gene signature consisting of five genes that had the greatest differential expression by stage from lung adenocarcinoma (LUAD) transcriptomes. The new gene signature enabled survival prognosis for multiple LUAD datasets from different platforms of transcriptomics and risk stratification for patients with and without a mutation in TP53 or EGFR, with high and low levels of PD‐L1, and with and without adjuvant chemotherapy treatment. Using these evaluations, it was also shown to be more robust compared to several other gene signatures. Functional analysis of the five genes and their protein‐protein interaction partners indicated that they are functionally enriched in cell cycle, endocytosis, and EGFR regulation, which are biological processes associated with lung cancer and drug resistance. Extensive discussions on related experimental studies suggest that the five genes are novel and sensible targets for developing new drugs and/or tackling drug resistance problems for LUAD.

LncRNA DLG2-AS1 as a Novel Biomarker in Lung Adenocarcinoma

“…To compare its specificity and sensitivity with other well-known cancer biomarkers [ 21 ] and cancer-related lncRNAs [ 18 ], we calculated the ROC curves of the EGFR, TP53, and TP53 genes, as well as the oncogenic lncRNAs MALAT-1 and NEAT1, using TCGA-LUAD data. We obtained AUC values of 0.539, 0.703, 0.542, and 0.573, respectively, which are considerably lower than the AUC values obtained for DLG2-AS1 ( Figure 2 b).…”

Characterization of the Immune Cell Infiltration Landscape Uncovers Prognostic and Immunogenic Characteristics in Lung Adenocarcinoma

“…TP53 mutation is not only the most common genetic event in NSCLC but also reported to be associated with poor prognosis in cancers, especially non-small cell lung cancer ( Ozaki and Nakagawara, 2011 ). TP53 mutation could affect disease progression, tumor cell characteristics, and the therapeutic effect of different therapeutics ( Wu and Hwang, 2019 ). In addition, the more enrichment of KEAP1 mutations in TMEscore high tumors than TMEscore low may be one potential explanation for the distinct performance of ICI efficacy in LUAD.…”

Proteome profiling of formalin‑fixed, paraffin‑embedded lung adenocarcinoma tissues using a tandem mass tag‑based quantitative proteomics approach

“…Marinelli et al ( 26 ) confirmed that the efficacy of immunotherapy had notable interpatient heterogeneity in patients with LUAD. In addition, immune checkpoint inhibitors were of benefit to a great deal patients with LUAD, and a small mutation panel of coding sequences could predict the long-term outcome of immunotherapy ( 27 ). In the current study, 19 differentially expressed membrane proteins were found to be associated with immune processes, indicating that these cell membrane proteins may be potential immunotherapeutic targets.…”