IMR Press / FBL / Volume 29 / Issue 4 / DOI: 10.31083/j.fbl2904135
Open Access Original Research
Prognostic Cell Death Index for Lung Adenocarcinoma: A Comprehensive Transcriptome-Based Analysis of Twelve Programmed Cell Death Pattern Genes
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1 Department of Thoracic and Cardiac Surgery, Longyan First Affiliated Hospital of Fujian Medical University, 364000 Longyan, Fujian, China
*Correspondence: (Jiehuan Lin)
Front. Biosci. (Landmark Ed) 2024, 29(4), 135;
Submitted: 23 September 2023 | Revised: 14 January 2024 | Accepted: 6 February 2024 | Published: 1 April 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Objective: Lung adenocarcinoma (LUAD) is a prominent contributor to global cancer mortality, characterized by constrained prognosis. This study aimed to develop a novel prognostic indicator, the Cell Death Index (CDI), utilizing twelve programmed cell death (PCD) pattern genes, to predict the immune infiltration and prognosis in LUAD patients. Methods: We collected PCD-related genes and identified prognostic PCD genes in the Cancer Genome Atlas (TCGA)-LUAD dataset, and made rigorous validation in the Clinical Proteomic Tumor Analysis Consortium (CPTAC)-LUAD cohorts. CDI was calculated using a multivariable Cox regression model. Functional enrichment and tumor microenvironment were evaluated. Drug sensitivity prediction and nomogram development were performed to assess CDI’s potential value. Results: The results revealed 10 PCD genes (ERO1A, CDK5R1, TRIM6, DNASE2B, ITPRIP, MRGPRX2, FGA, NDUFA13, NLRP2, and CD68) significantly associated with LUAD prognosis. The CDI was constructed and showed high accuracy in predicting patient survival with C-index values of 0.801 and 0.794 in the prognosis cohort and validation cohort, respectively. CDI is also indicative of variations in biological functions, tumor microenvironment, and immune cell infiltration including neutrophils, activated mast cells, activated dendritic cells, M0 macrophages, resting natural killer cells, γδT cells, and activated memory CD4+T cells. Furthermore, drug sensitivity analysis indicated potential targeted strategies. Conclusions: The CDI, based on PCD genes, serves as a robust prognostic tool for LUAD, offering profound insights into tumor biology, immune response, and personalized treatment strategies. This study underscores the pivotal role of PCD mechanisms in LUAD pathogenesis and identifies potential therapeutic targets.

lung adenocarcinoma
prognostic indicator
programmed cell death genes
immune infiltration
personalized treatment strategies

-This study introduces a novel prognostic indicator named the Cell Death Index (CDI), based on programmed cell death genes, for predicting immune infiltration and prognosis in LUAD patients.
-CDI exhibits remarkable accuracy in predicting patient survival, with C-index values of 0.801 and 0.794 in the prognosis cohort and validation cohort, respectively.
-The CDI, comprising ten programmed cell death genes, demonstrates a significant association with LUAD prognosis and offers insights into tumor biology, tumor microenvironment, and immune cell infiltration.

Fig. 1.
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