Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France.
Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France.
Biochim Biophys Acta Rev Cancer. 2021 Aug;1876(1):188538. doi: 10.1016/j.bbcan.2021.188538. Epub 2021 Apr 20.
Twenty mucin genes have been identified and classified in two groups (encoding secreted and membrane-bound proteins). Secreted mucins participate in mucus formation by assembling a 3-dimensional network via oligomerization, whereas membrane-bound mucins are anchored to the outer membrane mediating extracellular interactions and cell signaling. Both groups have been associated with carcinogenesis progression in epithelial cancers, and are therefore considered as potential therapeutic targets. In the present review, we discuss the link between mucin expression patterns and patient survival and propose mucins as prognosis biomarkers of epithelial cancers (esophagus, gastric, pancreatic, colorectal, lung, breast or ovarian cancers). We also investigate the relationship between mucin expression and overall survival in the TCGA dataset. In particular, epigenetic mechanisms regulating mucin gene expression, such as aberrant DNA methylation and histone modification, are interesting as they are also associated with diagnosis or prognosis significance. Indeed, mucin hypomethylation has been shown to be associated with carcinogenesis progression and was linked to prognosis in colon cancer or pancreatic cancer patients. Finally we describe the relationship between mucin expression and non-coding RNAs that also may serve as biomarkers. Altogether the concomitant knowledge of specific mucin-pattern expression and epigenetic regulation could be translated as biomarkers with a better specificity/sensitivity performance in several epithelial cancers.
已经鉴定出 20 种黏蛋白基因，并将其分为两组（编码分泌型和膜结合型蛋白）。分泌型黏蛋白通过寡聚化组装成三维网络，参与黏液的形成，而膜结合型黏蛋白通过锚定在外膜上，介导细胞外相互作用和细胞信号转导。这两组都与上皮性癌症的癌变进展有关，因此被认为是潜在的治疗靶点。在本综述中，我们讨论了黏蛋白表达模式与患者生存之间的联系，并提出黏蛋白作为上皮性癌症（食管癌、胃癌、胰腺癌、结直肠癌、肺癌、乳腺癌或卵巢癌）的预后生物标志物。我们还研究了 TCGA 数据集中黏蛋白表达与总生存期之间的关系。特别是，调节黏蛋白基因表达的表观遗传机制，如异常的 DNA 甲基化和组蛋白修饰，很有趣，因为它们也与诊断或预后意义相关。事实上，黏蛋白低甲基化已被证明与癌变进展有关，并与结肠癌或胰腺癌患者的预后相关。最后，我们描述了黏蛋白表达与非编码 RNA 的关系，非编码 RNA 也可以作为生物标志物。总之，特定黏蛋白模式表达和表观遗传调控的综合知识可以作为几种上皮性癌症中特异性/敏感性更好的生物标志物。
