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ORIGINAL RESEARCH article

Front. Med.
Sec. Gastroenterology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1403171
This article is part of the Research Topic Tumor Microenvironment and Personalized Therapy of Gastrointestinal Cancer View all 3 articles

Multi-Omics Analysis Reveals the Landscape of Tumor Microenvironments in Left-Sided and Right-Sided Colon Cancer

Provisionally accepted
Dongfang Liu Dongfang Liu Chen Li Chen Li *Zenghua Deng Zenghua Deng *Nan Luo Nan Luo *Wenxia Li Wenxia Li *Wenzhe Hu Wenzhe Hu *Xiang Li Xiang Li *Zichao Qiu Zichao Qiu *Jianfei Chen Jianfei Chen *Jirun Peng Jirun Peng *
  • Beijing Shijitan Hospital, Capital Medical University, Beijing, China

The final, formatted version of the article will be published soon.

    Background: Distinct clinical features and molecular characteristics of left-sided colon cancer(LCC) and right-sided colon cancer(RCC) suggest significant variations in their tumor microenvironments (TME). These differences can impact the efficacy of immunotherapy, making it essential to investigate and understand these disparities. Methods: We conducted a multi-omics analysis, including bulk RNA sequencing (bulk RNA-seq), single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing (WES), to investigate the constituents and characteristic differences of the tumor microenvironment (TME) in left-sided colon cancer (LCC) and right-sided colon cancer (RCC). Result: Deconvolution algorithms revealed significant differences in infiltrated immune cells between left-sided colon cancer (LCC) and right-sided colon cancer (RCC), including dendritic cells, neutrophils, natural killer (NK) cells, CD4 and CD8 T cells, and M1 macrophages (P < 0.05). Notably, whole-exome sequencing (WES) data analysis showed a significantly higher mutation frequency in RCC compared to LCC (82,187/162 versus 18,726/115, P < 0.01). Single-cell analysis identified predominant tumor cell subclusters in RCC characterized by heightened proliferative potential and increased expression of major histocompatibility complex class I molecules. However, the main CD8+ T cell subpopulations in RCC exhibited a highly differentiated state, marked by T cell exhaustion and recent activation, defined as tumor-specific cytotoxic T lymphocytes (CTLs). Immunofluorescence and flow cytometry results confirmed this trend. Additionally, intercellular communication analysis demonstrated a greater quantity and intensity of interactions between tumorspecific CTLs and tumor cells in RCC. Conclusion: RCC patients with an abundance of tumor-specific cytotoxic T lymphocytes (CTLs) and increased immunogenicity of tumor cells in the TME may be better candidates for immune checkpoint inhibitor therapy.

    Keywords: TME, colorectal cancer, Right-sided colon cancer, Left-sided colon cancer, immune therapy, PD-1, 1．Introduction

    Received: 19 Mar 2024; Accepted: 31 Jul 2024.

    Copyright: © 2024 Liu, Li, Deng, Luo, Li, Hu, Li, Qiu, Chen and Peng. 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) or licensor 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.

    * Correspondence:
    Chen Li, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
    Zenghua Deng, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
    Nan Luo, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
    Wenxia Li, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
    Wenzhe Hu, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
    Xiang Li, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
    Zichao Qiu, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
    Jianfei Chen, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
    Jirun Peng, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.