Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma

Linshan Xie; Hui Kong; Jinjie Yu; Mengting Sun; Shaohua Lu; Yong Zhang; Jie Hu; Fang Du; Qiuyu Lian; Hongyi Xin; Jian Zhou; Xiangdong Wang; Charles A. Powell; Fred R. Hirsch; Chunxue Bai; Yuanlin Song; Jun Yin; Dawei Yang

doi:10.1002/ctm2.1573

Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (2) : e1573 DOI: 10.1002/ctm2.1573

RESEARCH ARTICLE

Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma

Linshan Xie ¹
, Hui Kong ²
, Jinjie Yu ³^,⁴
, Mengting Sun ¹
, Shaohua Lu ²
, Yong Zhang ¹
, Jie Hu ¹
, Fang Du ⁵
, Qiuyu Lian ⁶
, Hongyi Xin ⁷
, Jian Zhou ¹^,⁸^,⁹^,¹⁰
, Xiangdong Wang ¹^,¹¹^,¹²
, Charles A. Powell ¹³
, Fred R. Hirsch ¹⁴
, Chunxue Bai ¹^,⁸^,⁹^,¹⁰
, Yuanlin Song ¹^,⁸^,⁹^,¹⁰
, Jun Yin ³^,^†
, Dawei Yang ¹^,⁸^,⁹^,¹⁰^,¹⁵^,^†

Author information +

¹. Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China

². Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

³. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

⁴. Department of Thoracic Surgery, Shanghai Geriatric Medical Center, Shanghai, China

⁵. Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China

⁶. Gurdon Institute, University of Cambridge, Cambridge, UK

⁷. Global Institute of Future Technology, Shanghai Jiao Tong University, Shanghai, China

⁸. Shanghai Engineer and Technology Research Center of Internet of Things for Respiratory Medicine, Shanghai, China

⁹. Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, China

¹⁰. Shanghai Respiratory Research Institution, Shanghai, China

¹¹. Shanghai Institute of Clinical Bioinformatics, Shanghai, China

¹². Shanghai Engineering Research for AI Technology for Cardiopulmonary Diseases, Fudan University Shanghai Medical College, Shanghai, China

¹³. Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA

¹⁴. Tisch Cancer Institute, Center for Thoracic Oncology, Mount Sinai Health System, New York, New York, USA

¹⁵. Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China

jun_yin@fudan.edu.cn

yang.dawei@zs-hospital.sh.cn

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Abstract

Background: Patients who possess various histological subtypes of early-stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early-stage LUAD due to intratumour intricacy.

Methods: We included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single-cell RNA sequencing (scRNA-seq) was carried out on matched tumour and normal tissue. Three formalin-fixed and paraffin-embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP).

Results: Using DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA-seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = -.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD-L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region.

Conclusions: These findings illustrate that assessing patient histological subtypes at the single-cell level is feasible. Additionally, tumour endothelial cells that express PD-L1 in stage IA LUAD suppress immune-responsive CD8+ T cells.

Keywords

digital spatial profiler / histological subtypes / lung adenocarcinoma / single-cell RNA sequencing / tumour endothelial cells

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Linshan Xie,Hui Kong,Jinjie Yu,Mengting Sun,Shaohua Lu,Yong Zhang,Jie Hu,Fang Du,Qiuyu Lian,Hongyi Xin,Jian Zhou,Xiangdong Wang,Charles A. Powell,Fred R. Hirsch,Chunxue Bai,Yuanlin Song,Jun Yin,Dawei Yang. Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma. Clinical and Translational Medicine, 2024, 14(2): e1573 DOI:10.1002/ctm2.1573

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2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.