Integrated single-nuclear RNA sequencing analysis reveals distinct characteristics of mucinous adenocarcinoma in right-sided colon cancer

Yunhua Xu; Guang Fu; Xiguang Chen; Rongfang He; Qing Fang; Xiangwen Tan; Kunming Xu; Hongming Li; Jie Tan; Min Fang; Kai Fu; Qiulin Huang; Shuai Xiao

doi:10.1016/j.ijbiomac.2025.142744

Integrated single-nuclear RNA sequencing analysis reveals distinct characteristics of mucinous adenocarcinoma in right-sided colon cancer

Int J Biol Macromol. 2025 May;309(Pt 1):142744. doi: 10.1016/j.ijbiomac.2025.142744. Epub 2025 Apr 1.

Authors

Yunhua Xu¹, Guang Fu², Xiguang Chen², Rongfang He³, Qing Fang⁴, Xiangwen Tan⁵, Kunming Xu⁴, Hongming Li², Jie Tan², Min Fang⁶, Kai Fu⁷, Qiulin Huang⁸, Shuai Xiao⁹

Affiliations

¹ The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China; The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China.
² The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.
³ The First Affiliated Hospital, Department of pathology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China.
⁴ The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China; The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.
⁵ The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China; The Second Affiliated Hospital, Department of hepatological Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China.
⁶ The First Affiliated Hospital, Department of Education and Training, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China.
⁷ Institute of Molecular Precision Medicine, Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China. Electronic address: fu_kai@csu.edu.cn.
⁸ The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China. Electronic address: 2018011993@usc.edu.cn.
⁹ The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China; The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, PR China; The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China. Electronic address: xiaoshuai1982@hotmail.com.

PMID: 40180102
DOI: 10.1016/j.ijbiomac.2025.142744

Abstract

Mucinous adenocarcinoma (MAC) is a unique histological subtype of colorectal cancer (CRC), which usually occurs in the right-sided colon with poor prognosis. Our previous studies reveled unique clinicopathological characteristic of MAC, but the distinct molecular features and tumor microenvironment (TME) characteristics remain clarify systematically. In this study, we conducted a single nuclear RNA sequencing (snRNA-seq) analysis for CRC tissues with different histological subtypes, including MAC, partial mucinous adenocarcinoma (pMAC) and non-specific adenocarcinoma (AC). Our results show that MAC has a unique transcriptome profile and a distinct single-cell characteristic. It exhibited a higher degree of tumor purity but a lower composition of TME. MAC had a distinct cell-cell communication microenvironment and a particular evolutionary trajectory. The EpithelialCells of MAC closely interacted with fibroblasts, endothelial cells, and mural cells clusters. Furthermore, molecular functional characteristics analysis revealed that MAC enriched EpithelialCells, Fibroblasts, and Endothelial cells clusters have a high active in glycolysis, inflammation, and angiogenesis respectively. This comprehensive study first demonstrated that MAC is a unique histological subtype of right-sided CRC in the single cell level, and elucidated its tumor microenvironment composition and biological function characteristics, which will help us better understand the intrinsic feature of MAC.

Keywords: Angiogenesis; Colorectal cancer; Glycolysis; Inflammation; Mucinous adenocarcinoma; Single nuclear RNA-seq.

MeSH terms

Adenocarcinoma, Mucinous* / genetics
Adenocarcinoma, Mucinous* / pathology
Colonic Neoplasms* / genetics
Colonic Neoplasms* / pathology
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Sequence Analysis, RNA* / methods
Single-Cell Analysis
Transcriptome
Tumor Microenvironment / genetics