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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1347770
This article is part of the Research Topic Application of Bioinformatics, Machine Learning, and Artificial Intelligence to Improve Diagnosis, Prognosis and Treatment of Cancer View all 5 articles

Exploring the Molecular and Immune Landscape of Cellular Senescence in Lung Adenocarcinoma Cellular Senescence in Lung Adenocarcinoma

Provisionally accepted
Kun Ru Kun Ru 1Liang Cui Liang Cui 2Cong Wu Cong Wu 3Xinxin Tan Xinxin Tan 4Yuting Ma Yuting Ma 1Yu Hao Yu Hao 1Xiao Xiao Xiao Xiao 4Jing Bai Jing Bai 2Xiang Liu Xiang Liu 5Xuefeng Xia Xuefeng Xia 2Miaoqing Zhao Miaoqing Zhao 1*
  • 1 Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
  • 2 Geneplus-Beijing Institute, Beijing, China
  • 3 Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
  • 4 Geneplus-Shenzhen, Guangdong, China
  • 5 Department of Thoracic Surgery, The Second Affiliated Hospital,Hengyang Medical School, University of South China, Hengyang, China

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

    The connection between aging and cancer is complex. Previous research has highlighted the association between the aging process of lung adenocarcinoma (LUAD) cells and the immune response, yet there remains a gap in confirming this through single-cell data validation. Here, we aim to develop a novel aging-related prognostic model for LUAD, and verify the alterations in the genome and immune microenvironment linked to cellular senescence. By exploring the expression profiles of 586 cellular senescence-related genes in 428 LUAD patients, we constructed an aging-related genes (ARGs) risk model included 10 ARGs and validated it as an independent prognostic predictor for LUAD patients. Notably, patients with low aging scores (LAS group) exhibited better survival, lower tumor mutation burden (TMB), lower somatic mutation frequency, lower tumor proliferation rate, and an immune activated phenotype compared to patients with high aging scores (HAS group). While the HAS group was enriched in tumor cells and showed a lower infiltration of CD8-CCR7, CD8-CXCL13, CD8-GNLY, FCGR3A NK cells, XCL1 NK cells, plasma cell (PC) and other immune subsets. Furthermore, the SPP1 and TENASCIN pathways, associated with tumor immune escape and tumor progression, were also enriched in the HAS group. Additionally, our study also indicated that senescence levels were heterogeneous in the LUAD tumor microenvironment (TME), especially with tumor cells in the LAS group showing higher age scores compared to those in the HAS group. Collectively, our findings underscore that ARRS through ARGs serves as a robust biomarker for the prognosis in LUAD.

    Keywords: cellular senescence, Lung Adenocarcinoma, Tumor Microenvironment, heterogeneity, machine learning

    Received: 01 Dec 2023; Accepted: 08 Aug 2024.

    Copyright: © 2024 Ru, Cui, Wu, Tan, Ma, Hao, Xiao, Bai, Liu, Xia and Zhao. 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: Miaoqing Zhao, Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.