Spatial transcriptomics reveals prognosis‐associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment

Author:

Yan Kai1,Liu Qing‐Zhi2,Huang Rong‐Rong1,Jiang Yi‐Hua13,Bian Zhen‐Hua4,Li Si‐Jin5,Li Liang6,Shen Fei5,Tsuneyama Koichi7,Zhang Qing‐Ling8,Lian Zhe‐Xiong9,Guan Haixia10,Xu Bo5ORCID

Affiliation:

1. Guangdong Cardiovascular Institute Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou China

2. Chronic Disease Laboratory Institutes for Life Sciences South China University of Technology Guangzhou China

3. Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application Guangzhou China

4. School of Biomedical Sciences and Engineering South China University of Technology Guangzhou International Campus Guangzhou China

5. Department of Thyroid Surgery Guangzhou First People's Hospital South China University of Technology Guangzhou China

6. Medical Research Institute Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou China

7. Department of Pathology and Laboratory Medicine Institute of Biomedical Sciences Tokushima University Graduate School Tokushima Japan

8. Department of Pathology Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou China

9. Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou China

10. Department of Endocrinology Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou China

Abstract

AbstractBackgroundPapillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study.MethodsIn conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC‐associated cells within the tissue sections. The spatial RNA‐clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand–receptor analysis and Gene Ontology enrichment analysis.ResultsThe spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse‐free survival in PTC patients. We discovered key ligand–receptor interactions, including LAMB3–ITGA2, FN1–ITGA3 and FN1–SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse‐free survival. In the tumour immune microenvironment, reduced interaction between myeloid‐derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA‐clinical analysis method developed here revealed prognosis‐associated cellular heterogeneity in the PTC microenvironment.ConclusionsThe occurrence of tumour foci No. 2 and three enhanced ligand–receptor interactions in the AFC area/tumour foci reduced the relapse‐free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.

Funder

National Natural Science Foundation of China

Guangzhou Municipal Science and Technology Bureau

Publisher

Wiley

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3