Gillies McIndoe Research Institute, Newtown, Newtown, Wellington, New Zealand.
School of Biological Sciences and Centre for Biodiscovery, Victoria University of Wellington, Kelburn, Wellington, New Zealand.
PLoS One. 2019 Sep 6;14(9):e0221963. doi: 10.1371/journal.pone.0221963. eCollection 2019.
The cancer stem cell concept proposes that tumor growth and recurrence is driven by a small population of cancer stem cells (CSCs). In this study we investigated the expression of induced-pluripotent stem cell (iPSC) markers and their localization in primary low-grade adenocarcinoma (LGCA) and high-grade adenocarcinoma (HGCA) and their patient-matched normal colon samples.
Transcription and translation of iPSC markers OCT4, SOX2, NANOG, KLF4 and c-MYC were investigated using immunohistochemical (IHC) staining, RT-qPCR and in-situ hybridization (ISH).
All five iPSC markers were detected at the transcriptional and translational levels. Protein abundance was found to be correlated with tumor grade. Based on their protein expression within the tumors, two sub-populations of cells were identified: a NANOG+/OCT4- epithelial subpopulation and an OCT4+/NANOG- stromal subpopulation. All cases were accurately graded based on four pieces of iPSC marker-related data.
This study suggests the presence of two putative sub-populations of CSCs: a NANOG+/OCT4- epithelial subpopulation and an OCT4+/NANOG- stromal subpopulation. Normal colon, LGCA and HGCA could be accurately distinguished from one another using iPSC marker expression. Once validated, novel combinations of iPSC markers may provide diagnostic and prognostic value to help guide patient management.
癌症干细胞概念提出，肿瘤的生长和复发是由一小部分癌症干细胞（CSC）驱动的。在这项研究中，我们研究了诱导多能干细胞（iPSC）标志物的表达及其在原发性低级别腺癌（LGCA）和高级别腺癌（HGCA）及其患者匹配的正常结肠样本中的定位。
使用免疫组织化学（IHC）染色、RT-qPCR 和原位杂交（ISH）研究 iPSC 标志物 OCT4、SOX2、NANOG、KLF4 和 c-MYC 的转录和翻译。
所有五种 iPSC 标志物在转录和翻译水平上均被检测到。蛋白丰度与肿瘤分级相关。根据它们在肿瘤中的蛋白表达，鉴定出两种细胞亚群：NANOG+/OCT4-上皮亚群和 OCT4+/NANOG-基质亚群。基于四种与 iPSC 标志物相关的数据，所有病例均被准确分级。
本研究表明存在两种假定的 CSC 亚群：NANOG+/OCT4-上皮亚群和 OCT4+/NANOG-基质亚群。使用 iPSC 标志物表达可以准确区分正常结肠、LGCA 和 HGCA。一旦得到验证，新型 iPSC 标志物组合可能具有诊断和预后价值，有助于指导患者管理。
