4.5 Article

Exonuclease 1 (EXO1) is a Potential Prognostic Biomarker and Correlates with Immune Infiltrates in Lung Adenocarcinoma

Journal

ONCOTARGETS AND THERAPY
Volume 14, Issue -, Pages 1033-1048

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S286274

Keywords

EXO1; lung adenocarcinoma; prognosis; biomarker; immune infiltration

Funding

  1. Natural Science Foundation of China [81802494]
  2. Shanghai Municipal Commission of Health and Family Planning [20184Y0107]

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The study found that EXO1 is highly expressed in LUAD and is associated with poor prognosis, potentially involving biological pathways such as cell cycle regulation, DNA repair, and immune response. Furthermore, it is correlated with levels of infiltrating immune cells in the tumor microenvironment, and knockdown of EXO1 may inhibit the migratory ability of lung cancer cells.
Background: Exonuclease 1 (EXO1) has been identified to be highly expressed in different human malignancies, but its expression and prognostic role in lung adenocarcinoma (LUAD) remain unknown. Materials and Methods: Two independent cohorts extracted from public databases and one cohort from our center were analyzed in this study. Expression levels of EXO1 in LUAD tissues and paired para-cancer tissues were detected. The prognostic value of EXO1 in LUAD patients was evaluated in the three cohorts. Enrichment analyses were performed to explore the possible underlying biological pathways. Moreover, we also explored the correlations between EXO1 and tumor-infiltrating immune cells and evaluated the impact of EXO1 knock-down on the migration of lung cancer cells. Results: In this study, we found that EXO1 was highly expressed in LUAD tissues compared with para-cancerous tissues in public databases (p < 0.01), which was consistent with our data (p < 0.01). Survival analysis indicated that high expression of EXO1 was associated with poor prognosis in LUAD (p < 0.01). Enrichment analyses indicated that biological pathways like cell cycle regulation, DNA damage and repair, immune response, neuroactive ligand-receptor interaction, may be associated with EXO1 aberrant expression. Moreover, high expression of EXO1 was correlated with decreased infiltrating B cells (p < 0.01) and CD4+ T cells (p < 0.01) levels, and low infiltrating levels of B cells (p < 0.01) and dendritic cells (DCs) (p < 0.05) indicated poor overall survival (OS) in LUAD. Additionally, in vitro experiments suggested that knockdown of EXO1 may inhibit the migratory ability of lung cancer cells. Conclusion: In conclusion, EXO1 is a potential prognostic biomarker in LUAD, and correlates with infiltrating levels of immune cells in the tumor microenvironment. Further prospective validation of EXO1 in lung cancer is warranted.

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