Xu Yunhua, Fu Guang, Chen Xiguang, He Rongfang, Fang Qing, Tan Xiangwen, Xu Kunming, Li Hongming, Tan Jie, Fang Min, Fu Kai, Huang Qiulin, Xiao Shuai
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.
Int J Biol Macromol. 2025 May;309(Pt 1):142744. doi: 10.1016/j.ijbiomac.2025.142744. Epub 2025 Apr 1.
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.
黏液腺癌（MAC）是结直肠癌（CRC）一种独特的组织学亚型，通常发生于右半结肠，预后较差。我们之前的研究揭示了MAC独特的临床病理特征，但不同的分子特征和肿瘤微环境（TME）特征仍有待系统阐明。在本研究中，我们对不同组织学亚型的CRC组织进行了单核RNA测序（snRNA-seq）分析，包括MAC、部分黏液腺癌（pMAC）和非特异性腺癌（AC）。我们的结果表明，MAC具有独特的转录组图谱和明显的单细胞特征。它表现出更高程度的肿瘤纯度，但TME的组成较低。MAC具有独特的细胞间通讯微环境和特定的进化轨迹。MAC的上皮细胞与成纤维细胞、内皮细胞和壁细胞簇密切相互作用。此外，分子功能特征分析显示，MAC富集的上皮细胞、成纤维细胞和内皮细胞簇分别在糖酵解、炎症和血管生成方面具有高活性。这项综合研究首次在单细胞水平证明MAC是右半CRC的一种独特组织学亚型，并阐明了其肿瘤微环境组成和生物学功能特征，这将有助于我们更好地理解MAC的内在特征。
