Liu Jianbo, Qiu Siyuan, Fu Xiaorui, Zhou Bin, Zu Ruijuan, Lv Zhaoying, Li Yuan, Yang Lie, Zhou Zongguang
Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Institute of Digestive Surgery of Sichuan University, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, China.
Curr Genomics. 2025;26(2):95-117. doi: 10.2174/0113892029312303240821080358. Epub 2024 Sep 2.
Colorectal mucinous adenocarcinoma (MC) differs from adenocarcinoma (AD) in clinical features and molecular characteristics. The current treatment of colorectal MC is not precise enough, and the molecular characteristics remain unclear. The study aims to explore the difference between colorectal MC and AD on the transcriptome level for the possibility of treating colorectal MC precisely.
The data of colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database was assessed, and then differential analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify the differential hub RNAs between colorectal MC and AD. Differential hub lncRNAs and hub RNA of significant modules were validated by quantitative real-time PCR (qRT-PCR) among different colon cancer cell lines.
In total, 1680 differential expressed RNAs (DERs) were found by comparing colorectal MC (52, 13.3%) with AD (340, 86.7%). Through the WGCNA, a mucin-associated RNA module was identified, while some others might be associated with unique immune progress. Finally, 6 differential hub RNAs in the mucin-associated RNA module ( and ) were validated by qRT-PCR and showed higher expression levels in mucin-producing colorectal cell lines (Ls174T and HT-29).
This study suggests that clinical treatments for colorectal MC should be differentiated from AD. Further exploration of enterocyte (goblet cell) differentiation with tumor genesis and the distinct immune progression of MC may help to identify key therapeutic targets for colorectal MC. Further research on the application of immunotherapy to colorectal MC is needed.
结直肠黏液腺癌（MC）在临床特征和分子特性方面与腺癌（AD）不同。目前结直肠MC的治疗不够精准，其分子特性仍不清楚。本研究旨在探索结直肠MC和AD在转录组水平上的差异，以期实现对结直肠MC的精准治疗。
评估来自癌症基因组图谱（TCGA）数据库的结直肠癌（CRC）患者数据，然后进行差异分析和加权基因共表达网络分析（WGCNA），以鉴定结直肠MC和AD之间的差异关键RNA。通过定量实时PCR（qRT-PCR）在不同结肠癌细胞系中验证差异关键长链非编码RNA（lncRNAs）和显著模块的关键RNA。
通过比较结直肠MC（52例，13.3%）和AD（340例，86.7%），共发现1680个差异表达RNA（DERs）。通过WGCNA，鉴定出一个黏蛋白相关RNA模块，而其他一些模块可能与独特的免疫进程相关。最后，通过qRT-PCR验证了黏蛋白相关RNA模块中的6个差异关键RNA，它们在产生黏蛋白的结直肠癌细胞系（Ls174T和HT-29）中表达水平更高。
本研究表明，结直肠MC的临床治疗应与AD区分开来。进一步探索肠上皮细胞（杯状细胞）分化与肿瘤发生以及MC独特的免疫进程，可能有助于确定结直肠MC的关键治疗靶点。需要对免疫疗法在结直肠MC中的应用进行进一步研究。
