Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer

Frontiers in Oncology

Oncology

Zhi-Ji Chen¹  Hong-Tao Liu¹  Li Zhou¹  Zhi-Hang Zhou¹  Si-Qi Liao¹  Li Zhong¹  Song He¹  Si-Yuan Chen²  Ling-Long Peng³  Qing-Liang Wang⁴ 

[1] Department of Gastroenterology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;Department of Gastroenterology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China;Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;Department of Pathology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;

关键词: colorectal cancer;    metastasis;    prognosis;    heterogeneity;    spatial transcriptomics;   

DOI  :  10.3389/fonc.2023.1089090

 received in 2022-11-23, accepted in 2023-01-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveLocal invasion is the first step of metastasis, the main cause of colorectal cancer (CRC)-related death. Recent studies have revealed extensive intertumoral and intratumoral heterogeneity. Here, we focused on revealing local invasion-related genes in CRC. MethodsWe used spatial transcriptomic techniques to study the process of local invasion in four CRC tissues. First, we compared the pre-cancerous, cancer center, and invasive margin in one section (S115) and used pseudo-time analysis to reveal the differentiation trajectories from cancer center to invasive margin. Next, we performed immunohistochemical staining for RPL5, STC1, AKR1B1, CD47, and HLA-A on CRC samples. Moreover, we knocked down AKR1B1 in CRC cell lines and performed CCK-8, wound healing, and transwell assays to assess cell proliferation, migration, and invasion.ResultsWe demonstrated that 13 genes were overexpressed in invasive clusters, among which the expression of CSTB and TM4SF1 was correlated with poor PFS in CRC patients. The ribosome pathway was increased, while the antigen processing and presentation pathway was decreased along CRC progression. RPL5 was upregulated, while HLA-A was downregulated along cancer invasion in CRC samples. Pseudo-time analysis revealed that STC1, AKR1B1, SIRPA, C4orf3, EDNRA, CES1, PRRX1, EMP1, PPIB, PLTP, SULF2, and EGFL6 were unpregulated along the trajectories. Immunohistochemic3al staining showed the expression of STC1, AKR1B1, and CD47 was increased along cancer invasion in CRC samples. Knockdown of AKR1B1 inhibited CRC cells’ proliferation, migration, and invasion.ConclusionsWe revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion.

【 授权许可】

Unknown   
Copyright © 2023 Liu, Chen, Peng, Zhong, Zhou, Liao, Chen, Wang, He and Zhou