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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1492725
This article is part of the Research Topic Novel Molecular Targets in Cancer Therapy View all 6 articles

The bioinformatics analysis and experimental validation of the carcinogenic role of EXO1 in lung adenocarcinoma

Provisionally accepted
Bohao Sun Bohao Sun 1Jing Zhang Jing Zhang 1*Nan Wang Nan Wang 2*Zhirong Zhang Zhirong Zhang 3*Yichen Wu Yichen Wu 1*Mengzhen Xie Mengzhen Xie 1*Yanmei Peng Yanmei Peng 1*Zhaochang Jiang Zhaochang Jiang 1*Shumei Wei Shumei Wei 1*
  • 1 Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • 2 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
  • 3 School of Life Sciences, Xiamen University, Xiamen, Fujian Province, China

The final, formatted version of the article will be published soon.

    Background: Exonuclease 1 (EXO1), a protein involved in mismatch repair and recombination processes, has been identified as a prognostic biomarker in lung adenocarcinoma (LUAD). Nevertheless, its role in LUAD progression remains elusive. This study seeks to elucidate the functional significance of EXO1 in LUAD and evaluate its potential as a therapeutic target.Patient RNA-seq and clinical data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Subsequently, a protein-protein interaction (PPI) network was constructed using differentially expressed genes (DEGs) to identify pivotal genes. Validation of the expression of signature genes was carried out through quantitative real-time PCR (qRT-PCR). Additionally, the association between EXO1 expression and clinical data was investigated. Immunohistochemistry was utilized to assess EXO1 expression in 93 cases of invasive pulmonary adenocarcinoma.Finally, cellular functional assays were conducted to investigate the impact of EXO1 on LUAD cells.Ten key molecules (PBK, ASPM, NCAPG, EXO1, MKI67, RRM2, AURKA, DLGAP5, UBE2C, and CDC6) exhibited significantly elevated expression levels in LUAD tissues. Moreover, elevated levels of EXO1 gene expression correlated strongly with advanced T, N, and M stages and were significantly associated with immune cell infiltration in LUAD. Furthermore, marked increases in EXO1 protein expression were observed in patients diagnosed with invasive pulmonary adenocarcinoma. Notably, patients diagnosed with invasive pulmonary adenocarcinoma who exhibited elevated EXO1 expression levels exhibited increased lymph node metastasis, pleural invasion, poor tumor differentiation, and advanced clinical stage. Additionally, this study employed wound healing assay and CCK-8 cell proliferation assays to investigate the significant role of EXO1 in promoting the growth and migration of lung adenocarcinoma cells.Conclusions: This study identified ten hub genes associated with the initiation and progression of LUAD. Additionally, EXO1 may serve as a prognostic marker for LUAD patients, offering new perspectives for clinical treatments.

    Keywords: LUAD, Exo1, Poor-prognosis predictor, Clinical stage, Bioinformatics analysis

    Received: 07 Sep 2024; Accepted: 04 Dec 2024.

    Copyright: © 2024 Sun, Zhang, Wang, Zhang, Wu, Xie, Peng, Jiang and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jing Zhang, Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    Nan Wang, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China
    Zhirong Zhang, School of Life Sciences, Xiamen University, Xiamen, 361102, Fujian Province, China
    Yichen Wu, Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    Mengzhen Xie, Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    Yanmei Peng, Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    Zhaochang Jiang, Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    Shumei Wei, Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

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