Single-Cell RNA-seq Analysis Reveals Dysregulated Cell-Cell Interactions in a Tumor Microenvironment Related to HCC Development

Author:

Liu Zhenhao123ORCID,Zhang Siwen345,Ouyang Jian3,Wu Dan6,Chen Lanming45,Zhou Wen12ORCID,Xie Lu37ORCID

Affiliation:

1. Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China

2. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; Key Laboratory of Carcinogenesis, National Health and Family Planning Commission; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China

3. Shanghai-MOST Key Laboratory of Health and Disease Genomics, Institute for Genome and Bioinformatics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China

4. Key Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai), China Ministry of Agriculture, College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China

5. College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China

6. Center for Biomedical Informatics, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, 200040, China

7. Bioinformatics Center, National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China

Abstract

The heterogeneity of tumor microenvironment (TME) of hepatocellular carcinoma (HCC) may relate to cell-cell interaction event (CCE) dysregulation and would affect therapeutic responses and clinical outcomes. To reveal the differentiation of CCEs in the liver tissue from healthy donors (HD) to HCC, scRNA-seq data of ~62000 cells from HD, paracancerous nontumor tissue (NT), and HCC were analyzed. The microenvironmental CCE landscape was constructed. Dysregulated cell types and changed molecular functions were identified with CCE alterations in HCC. Dysregulated CCEs which function as pivotal roles in tumorigenesis and development of HCC included SPP1-CD44, MIF-TNFRSF14, and VEGFA-NRP1. A CCE-based immune regulatory network was extracted to illustrate the mechanism of TME dysregulation. A prognostic signature based on CCE genes was identified and validated in independent datasets. Our study provided insights into the characteristics of the cross-talk between tumor cells and microenvironment in HCC and established a workflow strategy for CCE analyses based on scRNA-seq data.

Funder

Central South University

Publisher

Hindawi Limited

Subject

Biochemistry (medical),Clinical Biochemistry,Genetics,Molecular Biology,General Medicine

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