Single-cell RNA sequencing reveals distinct tumor microenvironment of ground glass nodules and solid nodules in lung adenocarcinoma

Xiaofeng Huang; Zhimeng Lu; Xuewei Jiang; Zhe Zhang; Kun Yan; Guiping Yu

doi:10.3389/fcell.2023.1198338

Single-cell RNA sequencing reveals distinct tumor microenvironment of ground glass nodules and solid nodules in lung adenocarcinoma

Front Cell Dev Biol. 2023 Sep 7:11:1198338. doi: 10.3389/fcell.2023.1198338. eCollection 2023.

Authors

Xiaofeng Huang¹, Zhimeng Lu^#¹, Xuewei Jiang¹, Zhe Zhang¹, Kun Yan¹, Guiping Yu¹

Affiliation

¹ Department of Cardiothoracic Surgery, Jiangyin Clinical College of Xuzhou Medical University, Jiangyin, China.

^# Contributed equally.

Abstract

Introduction: Lung adenocarcinoma (LUAD) is the most prevalent lung cancer. LUAD presents as ground glass nodules (GGN) and solid nodules (SN) in imaging studies. GGN is an early type of LUAD with good prognosis. However, SN exhibits a more malignant behavior than GGN, including worse pathological staging and tumor prognosis. The mechanism leading to the different malignancy levels of GGN and SN remains elusive. Methods: Three patients with GGN and three patients with SN diagnosed with early LUAD were enrolled. The tumor samples were digested to a single-cell suspension and analyzed using 10× Genomic Single-cell ribonucleic acid sequences (scRNA-seq) techniques. Results: A total of 15,902 cells were obtained and classified into nine major types. The tumor microenvironment (TME) was subsequently described in detail. ScRNA-seq revealed that ribosome-related pathways and cell adhesion played similar but distinct roles in the two groups. SN also had more active cell proliferation, enriched cell cycle regulatory pathways, and severe inflammatory responses. Conclusion: We observed changes in the cellular composition and transcriptomic profile of GGN and SN. The study improved the understanding of the underlying mechanisms of lung carcinogenesis and contributed to lung cancer prevention and treatment.

Keywords: ground glass nodule; lung adenocarcinoma; macrophage; single-cell RNA sequencing; solid nodule; tumor microenvironment.

Grants and funding

This study was supported by the Scientific Research Program of Wuxi City Health Commission (grant number Q202156), the Scientific Research Program of Jiangsu Provincial Health Commission (grant number M2020076), the Scientific Research Program of Wuxi City Science and Technology Association (grant number KX-22-B15), the Talent Program of Wuxi City Health Commission (grant number BJ2020104) and the Postgraduate Research and Practice Innovation Program of Jiangsu Provincial Department of Education (grant number SJCX22_1283).