Seo Jee-Woo, Kim Jae-Yoon, Ha Ye Jin, Tak Ka Hee, Kim Jeong-Hwan, Cho Young-Bum, Park Seong-Hwan, Yoon Yong Sik, Kim Chan Wook, Lee Jong Lyul, Kim Seon-Young, Kim Seon-Kyu
Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
Department of Bioscience, University of Science and Technology, Daejeon, Korea.
Br J Cancer. 2025 Jul 2. doi: 10.1038/s41416-025-03104-3.
Mucinous adenocarcinoma (MuC), a colorectal cancer (CRC) subtype, exhibits distinct molecular features and poorer response to chemoradiotherapy than non-mucinous adenocarcinoma (NMuC). Conventional treatments often fail to address CRC heterogeneity, particularly in stage II disease. Therefore, improved biomarkers for risk stratification and personalised treatment are needed.
We analysed gene expression and mutation data from 259 CRC samples to identify characteristics of MuC. A 23-gene risk score (MuC-RS) was developed and validated across four independent cohorts (n = 1157). Statistical analyses, including generalised linear model likelihood ratio tests, Kaplan-Meier curves, log-rank tests, and Cox regression models, evaluated the prognostic utility of the MuC-RS.
MuC showed significant upregulation of fibroblast-associated genes, pathways related to epithelial-mesenchymal transition, and mucin glycosylation. The MuC-RS effectively stratified patients into high-risk (MuC-H) and low-risk (MuC-L) groups, with multivariate analysis confirming its prognostic value (HR = 1.72, 95% CI = 1.31-2.25, P < 0.001). Stage II MuC-L patients had poorer outcomes after conventional chemotherapy, but responded better to immune checkpoint inhibitors (ICIs), linked to higher tumour mutation burden and immune activation.
The MuC-RS effectively predicts recurrence and guides personalised treatment in CRC, particularly benefiting stage II MuC patients through improved risk stratification and treatment selection.
黏液腺癌（MuC）是结直肠癌（CRC）的一种亚型，与非黏液腺癌（NMuC）相比，具有独特的分子特征，对放化疗的反应较差。传统治疗方法往往无法应对CRC的异质性，尤其是在II期疾病中。因此，需要改进用于风险分层和个性化治疗的生物标志物。
我们分析了259份CRC样本的基因表达和突变数据，以确定MuC的特征。开发了一个23基因风险评分（MuC-RS），并在四个独立队列（n = 1157）中进行了验证。包括广义线性模型似然比检验、Kaplan-Meier曲线、对数秩检验和Cox回归模型在内的统计分析评估了MuC-RS的预后效用。
MuC显示成纤维细胞相关基因、与上皮-间质转化相关的通路以及黏蛋白糖基化显著上调。MuC-RS有效地将患者分为高风险（MuC-H）和低风险（MuC-L）组，多变量分析证实了其预后价值（HR = 1.72，95% CI = 1.31-2.25，P < 0.001）。II期MuC-L患者在接受传统化疗后的预后较差，但对免疫检查点抑制剂（ICI）反应较好，这与较高的肿瘤突变负担和免疫激活有关。
MuC-RS有效地预测了CRC的复发并指导个性化治疗，特别是通过改进风险分层和治疗选择，使II期MuC患者受益。
