Development and validation of a novel epigenetic-related prognostic signature and candidate drugs for patients with lung adenocarcinoma

Abstract

Background: Epigenetic dysregulation has been increasingly proposed as a hallmark of cancer. Here, the aim of this study is to establish an epigenetic-related signature for predicting the prognosis of lung adenocarcinoma (LUAD) patients. Results: Five epigenetic-related genes (ERGs) (ARRB1, PARP1, PKM, TFDP1, and YWHAZ) were identified as prognostic hub genes and used to establish a prognostic signature. According our risk score system, LUAD patients were stratified into high and low risk groups, and patients in the high risk group had a worse prognosis. ROC analysis indicated that the signature was precise in predicting the prognosis. A new nomogram was constructed based on the five hub genes, which can predict the OS of every LUAD patients. The calibration curves showed that the nomogram had better accuracy in prediction. Finally, candidate drugs that aimed at hub ERGs were identified, which included 47 compounds. Conclusions: Our epigenetic-related signature nomogram can effectively and reliably predict OS of LUAD patients, also we provide precise targeted chemotherapeutic drugs. Methods: The genomic data and clinical data of LUAD cohort were downloaded from the TCGA database and ERGs were obtained from the EpiFactors database. GSE31210 and GSE50081 microarray datasets were included as independent external datasets. Univariate Cox, LASSO regression, and multivariate Cox analyses were applied to construct the epigenetic-related signature.

Identification of N7-methylguanosine related signature for prognosis and immunotherapy efficacy prediction in lung adenocarcinoma

“…After reviewing previous researches, we further compared the m 7 G related signature with other prognostic models, including 5-gene signature (Wang) ( 33 ), 4-gene signature (Wu) ( 34 ), 3-gene signature (Yue) ( 35 ), and 5-gene signature (Zhai) ( 36 ). In order to ensure comparability among models, the risk score of each LUAD sample in entire TCGA cohort was calculated with the same formula according to corresponding genes in four signatures, and then patients were categorized into two groups based on same cut-off value ( 37 ).…”

A novel prognostic signature of metastasis-associated genes and personalized therapeutic strategy for lung adenocarcinoma patients

“…To present potential candidate drugs, the CMap database was conducted to predict small molecule drugs on the base of the prognostic MAGs as previously described [ 9 ]. The correlation between hub MAGs expression and drug response was predicted by CellMiner database ( https://discover.nci.nih.gov/cellminer/ ) [ 56 ].…”

“…Although two studies have previously been conducted by our team to identify numerous biomarkers associated with the survival of LUAD for predicting prognosis, including metabolism-related genes [ 8 ] and epigenetic-related prognostic signature [ 9 ]. However, since most patients with advanced lung adenocarcinoma die of tumor recurrence and metastasis, it is particularly important to analyze the predictive genes related to recurrence and metastasis.…”

Comprehensive Analysis Reveals the Potential Roles of Transcription Factor Dp-1 in Lung Adenocarcinoma

“…COMMD9 acted on TFDP1 to enhance the p53 signaling pathway in non-small cell lung cancer (NSCLC) [ 16 ]. Five genes, including TFDP1, were used to establish a prognostic signature nomogram in LUAD [ 17 ]. However, there are few studies on the specific roles and molecular mechanisms of TFDP1 in LUAD.…”