Huang An, Shi Jingyi, Sun Zhuang, Yang Yong, Gao Zhaoya, Gu Jin
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China.
Front Oncol. 2023 Apr 27;13:1061785. doi: 10.3389/fonc.2023.1061785. eCollection 2023.
Mucinous adenocarcinoma (MAC) is a unique clinicopathological colorectal cancer (CRC) type that has been recognized as a separate entity from non-mucinous adenocarcinoma (NMAC), with distinct clinical, pathologic, and molecular characteristics. We aimed to construct prognostic signatures and identifying candidate biomarkers for patients with MAC.
Differential expression analysis, weighted correlation network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model were used to identify hub genes and construct a prognostic signature based on RNA sequencing data from TCGA datasets. The Kaplan-Meier survival curve, gene set enrichment analysis (GSEA), cell stemness, and immune infiltration were analyzed. Biomarker expression in MAC and corresponding normal tissues from patients operated in 2020 was validated using immunohistochemistry.
We constructed a prognostic signature based on ten hub genes. Patients in the high-risk group had significantly worse overall survival (OS) than patients in the low-risk group (p < 0.0001). We also found that ENTR1 was closely associated with OS (p = 0.016). ENTR1 expression was significantly positively correlated with cell stemness of MAC (p < 0.0001) and CD8+ T cell infiltration (p = 0.01), whereas it was negatively associated with stromal scores (p = 0.03). Finally, the higher expression of ENTR1 in MAC tissues than in normal tissues was validated.
We established the first MAC prognostic signature, and determined that ENTR1 could serve as a prognostic marker for MAC.
黏液腺癌（MAC）是一种独特的临床病理类型的结直肠癌（CRC），已被确认为与非黏液腺癌（NMAC）不同的实体，具有独特的临床、病理和分子特征。我们旨在构建预后特征并识别MAC患者的候选生物标志物。
使用差异表达分析、加权基因共表达网络分析（WGCNA）和最小绝对收缩和选择算子（LASSO）-Cox回归模型来识别核心基因，并基于来自TCGA数据集的RNA测序数据构建预后特征。分析了Kaplan-Meier生存曲线、基因集富集分析（GSEA）、细胞干性和免疫浸润。使用免疫组织化学验证了2020年接受手术的患者MAC及相应正常组织中的生物标志物表达。
我们基于10个核心基因构建了一个预后特征。高危组患者的总生存期（OS）明显低于低危组患者（p < 0.0001）。我们还发现ENTR1与OS密切相关（p = 0.016）。ENTR1表达与MAC的细胞干性（p < 0.0001）和CD8 + T细胞浸润（p = 0.0）显著正相关，而与基质评分呈负相关（p = 0.03）。最后，验证了ENTR1在MAC组织中的表达高于正常组织。
我们建立了首个MAC预后特征，并确定ENTR1可作为MAC的预后标志物。
