Background DOG1 (ANO1; TMEM16A) is a voltage-gated calcium-activated chloride and bicarbonate channel. DOG1 is physiologically expressed in Cajal cells, where it plays an important role in regulating intestinal motility and its expression is a diagnostic hallmark of gastrointestinal stromal tumors (GIST). Data on a possible role of DOG1 in pancreatic cancer are rare and controversial. The aim of our study was to clarify the prevalence of DOG1 expression in pancreatic cancer and to study its association with parameters of cancer aggressiveness. Methods DOG1 expression was analyzed by immunohistochemistry in 599 pancreatic cancers in a tissue microarray format and in 12 cases of pancreatitis on large tissue sections. Results DOG1 expression was always absent in normal pancreas but a focal weak expression was seen in four of 12 cases of pancreatitis. DOG1 expression was, however, common in pancreatic cancer. Membranous and cytoplasmic DOG1 expression in tumor cells was highest in pancreatic ductal adenocarcinomas (61% of 444 interpretable cases), followed by cancers of the ampulla Vateri (43% of 51 interpretable cases), and absent in 6 acinus cell carcinomas. DOG1 expression in tumor associated stroma cells was seen in 76 of 444 (17%) pancreatic ductal adenocarcinomas and in seven of 51 (14%) cancers of the ampulla Vateri. Both tumoral and stromal DOG1 expression were unrelated to tumor stage, grade, lymph node and distant metastasis, mismatch repair protein deficiency and the density of CD8 positive cytotoxic T-lymphocytes in the subgroups of ductal adenocarcinomas and cancers of ampulla Vateri. Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness.

中文翻译：

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DOG1 通常在胰腺腺癌中表达，但与癌症侵袭性无关

背景 DOG1（ANO1；TMEM16A）是电压门控钙激活氯离子和碳酸氢根通道。DOG1 在 Cajal 细胞中生理表达，在调节肠道蠕动方面发挥重要作用，其表达是胃肠道间质瘤 (GIST) 的诊断标志。关于 DOG1 在胰腺癌中可能发挥的作用的数据很少且存在争议。我们研究的目的是阐明胰腺癌中 DOG1 表达的患病率，并研究其与癌症侵袭性参数的关系。方法采用免疫组织化学方法对组织微阵列格式的 599 例胰腺癌和 12 例胰腺炎大组织切片中的 DOG1 表达进行分析。结果 DOG1在正常胰腺组织中始终不表达，12例胰腺炎组织中有4例呈局灶性弱表达。然而，DOG1 表达在胰腺癌中很常见。肿瘤细胞膜和细胞质 DOG1 表达在胰腺导管腺癌中最高（444 个可解释病例中的 61%），其次是壶腹癌（51 个可解释病例中的 43%），而在 6 个腺泡细胞癌中不表达。在 444 例胰腺导管腺癌中的 76 例（17%）和 51 例壶腹癌中的 7 例（14%）中观察到肿瘤相关基质细胞中 DOG1 的表达。肿瘤和间质DOG1表达与导管腺癌和壶腹癌亚组中的肿瘤分期、分级、淋巴结和远处转移、错配修复蛋白缺陷以及CD8阳性细胞毒性T淋巴细胞的密度无关。总体而言，我们的研究结果表明 DOG1 可能代表胰腺癌诊断的潜在生物标志物和胰腺癌的假定治疗靶点。然而，DOG1 表达与胰腺癌侵袭性无关。