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Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer
OBJECTIVE: Local 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. METHODS: We used spatial transcri...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928961/ https://www.ncbi.nlm.nih.gov/pubmed/36816947 http://dx.doi.org/10.3389/fonc.2023.1089090 |
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author | Liu, Hong-Tao Chen, Si-Yuan Peng, Ling-Long Zhong, Li Zhou, Li Liao, Si-Qi Chen, Zhi-Ji Wang, Qing-Liang He, Song Zhou, Zhi-Hang |
author_facet | Liu, Hong-Tao Chen, Si-Yuan Peng, Ling-Long Zhong, Li Zhou, Li Liao, Si-Qi Chen, Zhi-Ji Wang, Qing-Liang He, Song Zhou, Zhi-Hang |
author_sort | Liu, Hong-Tao |
collection | PubMed |
description | OBJECTIVE: Local 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: We revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion. |
format | Online Article Text |
id | pubmed-9928961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99289612023-02-16 Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer Liu, Hong-Tao Chen, Si-Yuan Peng, Ling-Long Zhong, Li Zhou, Li Liao, Si-Qi Chen, Zhi-Ji Wang, Qing-Liang He, Song Zhou, Zhi-Hang Front Oncol Oncology OBJECTIVE: Local 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: We revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion. Frontiers Media S.A. 2023-02-01 /pmc/articles/PMC9928961/ /pubmed/36816947 http://dx.doi.org/10.3389/fonc.2023.1089090 Text en Copyright © 2023 Liu, Chen, Peng, Zhong, Zhou, Liao, Chen, Wang, He and Zhou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Liu, Hong-Tao Chen, Si-Yuan Peng, Ling-Long Zhong, Li Zhou, Li Liao, Si-Qi Chen, Zhi-Ji Wang, Qing-Liang He, Song Zhou, Zhi-Hang Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer |
title | Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer |
title_full | Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer |
title_fullStr | Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer |
title_full_unstemmed | Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer |
title_short | Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer |
title_sort | spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928961/ https://www.ncbi.nlm.nih.gov/pubmed/36816947 http://dx.doi.org/10.3389/fonc.2023.1089090 |
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