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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Thoracic Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1473437

Prognostic Determinants and Functional Role of PIK3C2G in Stage IIb-IIIa Lung Adenocarcinoma: Insights from Clinical and Molecular Analyses

Provisionally accepted
Chao Gao Chao Gao Jiaqi Zhang Jiaqi Zhang Xin Du Xin Du Xuehan Gao Xuehan Gao Xiayao Diao Xiayao Diao Ke Zhao Ke Zhao Yeye Chen Yeye Chen *Shanqing Li Shanqing Li *
  • Department of Thoracic Surgery, Peking Union Medical College Hospital (CAMS), Beijing, China

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

    To investigate the prognostic factors for stage IIb and IIIa lung adenocarcinoma following radical surgery and to explore the molecular mechanisms underlying these prognostic markers, focusing on the role of PIK3C2G.A retrospective analysis of patients with stage IIb or IIIa lung adenocarcinoma who underwent radical surgery between January 2017 and June 2023 was conducted. Baseline clinical and pathological data, surgical methods, and postoperative treatments were analyzed to assess overall survival (OS). Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors. Whole-exome sequencing (WES) was performed on a subset of the patients with preserved tumor tissues and no matched targeted therapies to identify high-frequency mutated genes. Functional experiments in A549 lung adenocarcinoma cells were performed to evaluate the role of the significant genes in tumor progression through cell proliferation, migration, invasion, apoptosis, and cell cycle assays.The survival analysis of 877 stage IIb and IIIa lung adenocarcinoma cases revealed significant differences in clinical characteristics and outcomes. Stage IIb patients had a median OS of 58 months compared to 37 months for stage IIIa, with 5-year OS rates of 46.9% and 30.5%, respectively. Univariate and multivariate Cox regression identified pathological stage, number of positive lymph nodes, age, and targeted therapy as independent prognostic factors.WES of 184 patients with no matched targeted therapies revealed high-frequency mutations in genes such as TP53 and PIK3C2G, with the latter emerging as the most significant prognostic marker. Functional assays demonstrated that the knockdown of PIK3C2G in A549 cells significantly reduced proliferation, migration and invasion while promoting apoptosis and disrupting cell cycle progression.PIK3C2G was identified as a significant prognostic marker in stage IIb and IIIa lung adenocarcinoma, with functional data supporting its therapeutic potential. Taken together, this study integrates clinical and molecular findings, which could be used as a reference to guide personalized treatment strategies.

    Keywords: Lung Adenocarcinoma, Stage IIb and IIIa, Whole-exome sequencing, PIK3C2G, targeted therapy

    Received: 31 Jul 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Gao, Zhang, Du, Gao, Diao, Zhao, Chen and Li. 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:
    Yeye Chen, Department of Thoracic Surgery, Peking Union Medical College Hospital (CAMS), Beijing, China
    Shanqing Li, Department of Thoracic Surgery, Peking Union Medical College Hospital (CAMS), Beijing, China

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