Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3169-3192
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3169
Multi-Omics analysis elucidates tumor microenvironment and intratumor microbes of angiogenesis subtypes in colon cancer
Yi Yang, Yu-Ting Qiu, Wen-Kun Li, Zi-Lu Cui, Shuo Teng, Ya-Dan Wang, Jing Wu
Yi Yang, Yu-Ting Qiu, Wen-Kun Li, Zi-Lu Cui, Shuo Teng, Jing Wu, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, China
Shuo Teng, Ya-Dan Wang, Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100050, China
Co-first authors: Yi Yang and Yu-Ting Qiu.
Co-corresponding authors: Jing Wu and Ya-Dan Wang.
Author contributions: Yang Y designed research, analyzed data and wrote the paper; Qiu YT analyzed data; Li WK analyzed data; Cui ZL wrote the paper; Teng S wrote the paper; Wang YD designed research and wrote the paper; Wu J designed research and wrote the paper. Yang Y and Qiu YT contributed equally to this study. Wu J and Wang YD are designated as co-corresponding authors. First, the research was performed as a collaborative effort, and the designation of co-corresponding authors authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper. This also ensures effective communication and management of post-submission matters, ultimately enhancing the paper's quality and reliability. Second, the overall research team encompassed authors with a variety of expertise and skills from different fields, and the designation of co-corresponding authors best reflects this diversity. This also promotes the most comprehensive and in-depth examination of the research topic, ultimately enriching readers' understanding by offering various expert perspectives.
Supported by Beijing Science and Technology Program, No. Z211100002921028; and Capital’s Funds for Health Improvement and Research, No. CFH2022-2-2025.
Institutional review board statement: The study was approved by the Medical Ethics Committee of Beijing Shijitan Hospital, Capital Medical University (Approval number: 2020–11).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data available on request from the authors.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Wu, DO, MD, PhD, Dean, Doctor, Professor, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, No. 59 Yong’an Road, Xicheng District, Beijing 100050, China. wujing36youyi@ccmu.edu.cn
Received: January 19, 2024
Revised: February 13, 2024
Accepted: May 6, 2024
Published online: July 15, 2024
Processing time: 175 Days and 8.5 Hours
Abstract
BACKGROUND

Angiogenesis plays an important role in colon cancer (CC) progression.

AIM

To investigate the tumor microenvironment (TME) and intratumor microbes of angiogenesis subtypes (AGSs) and explore potential targets for antiangiogenic therapy in CC.

METHODS

The data were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database. K-means clustering was used to construct the AGSs. The prognostic model was constructed based on the differential genes between two subtypes. Single-cell analysis was used to analyze the expression level of SLC2A3 on different cells in CC, which was validated by immunofluorescence. Its biological functions were further explored in HUVECs.

RESULTS

CC samples were grouped into two AGSs (AGS-A and AGS-B) groups and patients in the AGS-B group had poor prognosis. Further analysis revealed that the AGS-B group had high infiltration of TME immune cells, but also exhibited high immune escape. The intratumor microbes were also different between the two subtypes. A convenient 6-gene angiogenesis-related signature (ARS), was established to identify AGSs and predict the prognosis in CC patients. SLC2A3 was selected as the representative gene of ARS, which was higher expressed in endothelial cells and promoted the migration of HUVECs.

CONCLUSION

Our study identified two AGSs with distinct prognoses, TME, and intratumor microbial compositions, which could provide potential explanations for the impact on the prognosis of CC. The reliable ARS model was further constructed, which could guide the personalized treatment. The SLC2A3 might be a potential target for antiangiogenic therapy.

Keywords: Angiogenesis; Colon cancer; Immunotherapy; K-means; Single-cell analysis

Core Tip: Angiogenesis plays an important role in colon cancer (CC) progression. This study identified two angiogenesis subtypes (AGSs) with significantly different prognoses, tumor microenvironment, intratumor microbiota, drug sensitivity, and cancer-related pathways single-sample gene set enrichment analysis scores in patients with CC. Based on the two AGSs, a convenient 6-gene angiogenesis-related signature (ARS), was established to predict the prognosis in CC patients. SLC2A3 was selected as the representative gene of ARS, which was higher expressed in endothelial cells and promoted the migration of HUVECs.