Immune microenvironment analysis and novel biomarkers of early-stage lung adenocarcinoma evolution

Jun Liu; Yaxin Ji; Xiaodan Weng; Wei Shao; Jiaping Zhao; Hanlin Chen; Lu Shen; Fufeng Wang; Qi Meng; Xue Wu; Xiaonan Wang; Qiuxiang Ou; Honggang Ke

doi:10.3389/fonc.2023.1150098

Immune microenvironment analysis and novel biomarkers of early-stage lung adenocarcinoma evolution

Front Oncol. 2023 Jun 23:13:1150098. doi: 10.3389/fonc.2023.1150098. eCollection 2023.

Authors

Jun Liu¹, Yaxin Ji², Xiaodan Weng³, Wei Shao², Jiaping Zhao², Hanlin Chen⁴, Lu Shen⁴, Fufeng Wang⁴, Qi Meng⁴, Xue Wu⁴, Xiaonan Wang⁴, Qiuxiang Ou⁴, Honggang Ke³

Affiliations

¹ Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, China.
² Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
³ Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
⁴ Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China.

Abstract

Background: Lung cancer is the deadliest and most diagnosed type of cancer worldwide. The 5-year survival rate of lung adenocarcinoma (LUAD) dropped significantly when tumor stages advanced. Patients who received surgically resecting at the pre-invasive stage had a 5-year survival rate of nearly 100%. However, the study on the differences in gene expression profiles and immune microenvironment among pre-invasive LUAD patients is still lacking.

Methods: In this study, the gene expression profiles of three pre-invasive LUAD stages were compared using the RNA-sequencing data of 10 adenocarcinoma in situ (AIS) samples, 12 minimally invasive adenocarcinoma (MIA) samples, and 10 invasive adenocarcinoma (IAC) samples.

Results: The high expression levels of PTGFRN (Hazard Ratio [HR] = 1.45; 95% Confidence Interval [CI]: 1.08-1.94; log-rank P = 0.013) and SPP1 (HR = 1.44; 95% CI: 1.07-1.93; log-rank P = 0.015) were identified to be associated with LUAD prognosis. Moreover, the early LUAD invasion was accompanied by the enhancement of antigen presentation ability, reflected by the increase of myeloid dendritic cells infiltration rate (Cuzick test P < 0.01) and the upregulation of seven important genes participating in the antigen presentation, including HLA-A (Cuzick test P = 0.03), MICA (Cuzick test P = 0.01), MICB (Cuzick test P = 0.01), HLA-DPA1 (Cuzick test P = 0.04), HLA-DQA2 (Cuzick test P < 0.01), HLA-DQB1 (Cuzick test P = 0.03), and HLA-DQB2 (Cuzick test P < 0.01). However, the tumor-killing ability of the immune system was inhibited during this process, as there were no rising cytotoxic T cell activity (Cuzick test P = 0.20) and no increasing expression in genes encoding cytotoxic proteins.

Conclusion: In all, our research elucidated the changes in the immune microenvironment during early-stage LUAD evolution and may provide a theoretical basis for developing novel early-stage lung cancer therapeutic targets.

Keywords: RNA-sequencing; biomarkers; early-stage lung adenocarcinoma; immune microenvironment; tumor evolution.

Grants and funding

This study was supported in part by the Beijing Life Oasis Public Service Center(cphcf-02022-026).