Establishment and validation of an eight-gene metabolic–related prognostic signature model for lung adenocarcinoma

Ma, Weishuang; Liang, Jiaming; Liu, Jinhui; Tian, Dan; Chen, Zisheng

doi:10.18632/aging.202681

Cited by 8 publications

(8 citation statements)

References 38 publications

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“…Liang et al discovered a novel ferroptosisrelated prognostic gene signature for hepatocellular carcinoma (15). Several studies have identified prognostic gene signatures of LUAD involving glycolysis (16), metabolism (17), or immunity (18). These studies did not explain the role of ferroptosis in their models.…”

Section: Introductionmentioning

confidence: 99%

Prognostic and immune implications of a novel ferroptosis-related ten-gene signature in lung adenocarcinoma

Ma¹,

Li²,

Luo³

2021

Ann Transl Med

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Background: Lung cancer has been the focus of attention for many researchers in recent years due to its leading contribution to cancer-related death worldwide, with lung adenocarcinoma (LUAD) being the most common histological type. Ferroptosis, a novel iron-dependent form of regulated cell death, can be induced by sorafenib. Emerging evidence shows that triggering ferroptosis has potential as a cancer therapy. This work aimed to build a ferroptosis-related gene signature for predicting the outcome of LUAD.Methods: The TCGA-LUAD dataset was set as the training cohort, and the GSE72094 and GSE68465 datasets were set as the validation cohorts. Sixty-two ferroptosis-related genes were retrieved from the literature. A univariate Cox regression model was constructed for the training cohort to preliminarily screen for potential prognostic ferroptosis-related genes. A gene signature was generated from a LASSO Cox regression model and assessed with the training and validation cohorts through Kaplan-Meier, Cox, and ROC analyses. In addition, the correlation between the risk score and autophagy-related genes was determined by the Pearson test. Finally, GSEA and immune infiltrating analyses were performed to better study the functional annotation of the signature and the role of each kind of immune cell.Results: A ten-gene signature was constructed from the training cohort and validated in three cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognostic value in LUAD. Moreover, a ROC analysis conducted with all cohort data confirmed the predictive ability of the ten-gene signature for LUAD prognosis. A total of 62.85% (308/490) of autophagy-related genes were found to be significantly correlated with risk scores. GSEA detailed the exact pathways related to the gene signature, and immuneinfiltrating analyses identified crucial roles for resting mast cells and resting dendritic cells in the prognosis of LUAD. Conclusions:We identified a novel ferroptosis-related ten-gene signature (PHKG2, PGD, PEBP1, NCOA4, GLS2, CISD1, ATP5G3, ALOX15, ALOX12B, and ACSL3) that can accurately predict LUAD prognosis and is closely linked to resting mast cells and resting dendritic cells.

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Section: Introductionmentioning

confidence: 99%

Prognostic and immune implications of a novel ferroptosis-related ten-gene signature in lung adenocarcinoma

Ma¹,

Li²,

Luo³

2021

Ann Transl Med

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“…In human hepatocellular carcinoma, Chinnadurai et al implicated IDO1 and PD-L1 as players in T cell suppression in this setting by investigating RNA expression of IDO/TDO and a set of B7 ligands. Lastly, in a retrospective study of non-small cell lung cancer (NSCLC), Mandarano et al report a correlation between elevated levels of IDO2 and poor prognosis, a finding recently confirmed by another group (9).…”

Section: Targeting Indoleamine 23-dioxygenases and Tryptophan Dioxygenase For Cancer Immunotherapymentioning

confidence: 85%

“…Lastly, in a retrospective study of non-small cell lung cancer (NSCLC), Mandarano et al. report a correlation between elevated levels of IDO2 and poor prognosis, a finding recently confirmed by another group ( 9 ).…”

mentioning

confidence: 85%

Editorial: Targeting Indoleamine 2,3-dioxygenases and Tryptophan Dioxygenase for Cancer Immunotherapy

Brochez

Krüse²,

Schadendorf³

et al. 2021

Front. Immunol.

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“…As a major component of the tumor microenvironment (TME), immune infiltration has been shown to contribute to tumor progression and the immunotherapeutic response ( Balkwill et al, 2012 ), and tumor-infiltrating immune cells, particularly T cells, are the cellular basis of immunotherapy. A better understanding of immune cells in the TME is critical to deciphering the mechanisms of immunotherapy, defining predictive biomarkers, and identifying new therapeutic targets ( Zhang and Zhang, 2020 ; Ma et al, 2021 ). In our GO analysis, most of the enriched functional terms were immune-related, and the same results were obtained by KEGG analysis.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Prognostic Signature Associated With the Homeobox Gene Family for Bladder Cancer

Dong

Liang

Ding

et al. 2021

Front. Mol. Biosci.

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Background: Bladder cancer (BLCA) is a common malignant tumor of the genitourinary system, and there is a lack of specific, reliable, and non-invasive tumor biomarker tests for diagnosis and prognosis evaluation. Homeobox genes play a vital role in BLCA tumorigenesis and development, but few studies have focused on the prognostic value of homeobox genes in BLCA. In this study, we aim to develop a prognostic signature associated with the homeobox gene family for BLCA.Methods: The RNA sequencing data, clinical data, and probe annotation files of BLCA patients were downloaded from the Gene Expression Omnibus database and the University of California, Santa Cruz (UCSC), Xena Browser. First, differentially expressed homeobox gene screening between tumor and normal samples was performed using the “limma” and robust rank aggregation (RRA) methods. The mutation data were obtained with the “TCGAmutation” package and visualized with the “maftools” package. Kaplan–Meier curves were plotted with the “survminer” package. Then, a signature was constructed by logistic regression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using “clusterProfiler.” Furthermore, the infiltration level of each immune cell type was estimated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Finally, the performance of the signature was evaluated by receiver-operating characteristic (ROC) curve and calibration curve analyses.Results: Six genes were selected to construct this prognostic model: TSHZ3, ZFHX4, ZEB2, MEIS1, ISL1, and HOXC4. We divided the BLCA cohort into high- and low-risk groups based on the median risk score calculated with the novel signature. The overall survival (OS) rate of the high-risk group was significantly lower than that of the low-risk group. The infiltration levels of almost all immune cells were significantly higher in the high-risk group than in the low-risk group. The average risk score for the group that responded to immunotherapy was significantly lower than that of the group that did not.Conclusion: We constructed a risk prediction signature with six homeobox genes, which showed good accuracy and consistency in predicting the patient’s prognosis and response to immunotherapy. Therefore, this signature can be a potential biomarker and treatment target for BLCA patients.

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Establishment and validation of an eight-gene metabolic–related prognostic signature model for lung adenocarcinoma

Cited by 8 publications

References 38 publications

Prognostic and immune implications of a novel ferroptosis-related ten-gene signature in lung adenocarcinoma

Prognostic and immune implications of a novel ferroptosis-related ten-gene signature in lung adenocarcinoma

Editorial: Targeting Indoleamine 2,3-dioxygenases and Tryptophan Dioxygenase for Cancer Immunotherapy

Identification of a Prognostic Signature Associated With the Homeobox Gene Family for Bladder Cancer

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