DCLK1 as a Marker/Indicator of Stem Cell Response in Barrett’s Esophagus/Esophageal Adenocarcinoma

The hypotheses are: 1) the intestinal stem cell marker, DCLK1, which is increased in both the epithelium and stroma in colon cancer is also increased in BE (Barrett’s esophagus) with HGD (high grade dysplasia) and in EAC (esophageal adenocarcinoma), 2) this expression correlates with disease progression towards EAC and 3) eradication of cells expressing stem cell markers occurs after therapy of EMR (endoscopic mucosal resection) or RFA (radiofrequency ablation) to eradicate BE with HGD and intramucosal adenocarcinoma and esophagectomy for EAC. We will test our hypotheses with the following aims: 1) To characterize the cell specific expression patterns of intestinal stem cell biomarkers in BE patients and correlate them with serum expression and disease progression, 2) To examine prospectively the effects of EMR, RFA or esophagectomy on the expression of stem cell biomarkers and the progression to EAC.

本研究的假设如下：1）在结肠癌上皮与间质中均表达上调的肠干细胞标志物（intestinal stem cell marker）DCLK1，在伴高级别异型增生（high grade dysplasia，缩写HGD）的巴雷特食管（Barrett’s esophagus，缩写BE）及食管腺癌（esophageal adenocarcinoma，缩写EAC）中同样表达上调；2）该标志物的表达与疾病向食管腺癌进展的进程呈相关性；3）针对伴高级别异型增生与黏膜内腺癌的巴雷特食管行内镜黏膜切除术（endoscopic mucosal resection，缩写EMR）或射频消融术（radiofrequency ablation，缩写RFA），以及针对食管腺癌行食管切除术治疗后，表达干细胞标志物的细胞可被清除。本研究将通过以下研究目标验证上述假设：1）明确肠干细胞生物标志物在巴雷特食管患者中的细胞特异性表达模式，并将其与血清表达水平及疾病进展相关联；2）前瞻性考察内镜黏膜切除术、射频消融术或食管切除术对干细胞生物标志物表达及向食管腺癌进展进程的影响。