Department of Medicine, Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
Dig Dis Sci. 2015 Feb;60(2):509-13. doi: 10.1007/s10620-014-3347-4. Epub 2014 Oct 5.
Doublecortin-like kinase 1 (DCLK1), a putative tumor stem cell marker has been shown to be highly expressed in the stromal and epithelial compartments in colon and pancreatic cancer as well as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC).
To prospectively investigate whether the immunohistochemical expression of DCLK1 was associated with detectable DCLK1 plasma expression in patients with existing BE and EAC.
Immunohistochemistry was performed on paraffin-embedded sections using DCLK1 antibody and scored based on staining intensity and tissue involvement. Purified human plasma samples were subjected to Western blot and ELISA analysis.
Forty (40) patients were enrolled: 10 controls (normal endoscopy) and 30 with BE/EAC (13 nondysplastic BE [NDBE], 9 dysplastic BE [DBE] and 8 EAC). Mean epithelial DCLK1 staining was as follows: controls = 0.11, NDBE = 3.83, DBE = 6.0, EAC = 7.17. Mean stromal DCLK1 staining was as follows: NDBE = 5.83, DBE = 5.375, EAC = 10.83. DCLK1 was detected by plasma Western blot in 1 control and in all patients with BE/EAC p < 0.0005. Plasma DCLK1 was elevated by ELISA in EAC compared to other groups, p < 0.05.
Increased expression of DCLK1 was observed in the epithelium, stroma and plasma of patients with BE/EAC. Furthermore, the presence of detectable DCLK1 in plasma of BE/EAC patients may provide a less invasive, detection tool in those patients as well as represent a novel molecular marker distinguishing between normal esophageal mucosa and BE or EAC.
双皮质激酶 1（DCLK1），一种假定的肿瘤干细胞标志物，已被证明在结肠癌、胰腺癌以及巴雷特食管（BE）和食管腺癌（EAC）的基质和上皮细胞中高度表达。
前瞻性研究现有的 BE 和 EAC 患者中，DCLK1 的免疫组织化学表达是否与可检测的 DCLK1 血浆表达相关。
使用 DCLK1 抗体对石蜡包埋切片进行免疫组织化学染色，并根据染色强度和组织受累进行评分。纯化的人血浆样本进行 Western blot 和 ELISA 分析。
共纳入 40 例患者：10 例对照（正常内镜）和 30 例 BE/EAC（13 例非异型增生 BE [NDBE]、9 例异型增生 BE [DBE]和 8 例 EAC）。上皮 DCLK1 染色的平均值如下：对照组=0.11，NDBE=3.83，DBE=6.0，EAC=7.17。基质 DCLK1 染色的平均值如下：NDBE=5.83，DBE=5.375，EAC=10.83。在 1 例对照和所有 BE/EAC 患者中，通过血浆 Western blot 检测到 DCLK1，p<0.0005。与其他组相比，EAC 患者的血浆 DCLK1 通过 ELISA 升高，p<0.05。
在 BE/EAC 患者的上皮、基质和血浆中观察到 DCLK1 的表达增加。此外，在 BE/EAC 患者的血浆中检测到可检测的 DCLK1 可能为这些患者提供一种侵入性更小的检测工具，并代表一种区分正常食管黏膜和 BE 或 EAC 的新型分子标志物。
