DOG1 is commonly expressed in pancreatic adenocarcinoma but unrelated to cancer aggressiveness

Abstract

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.

Ano1 is a Prognostic Biomarker That is Correlated with Immune Infiltration in Colorectal Cancer

“…34,35 ANO1, which encodes a 960-amino acid protein with 8 transmembrane domains, is highly deregulated in different tumors. 7,8,13,36 As an oncogenic factor, Ano1 can promote cell movement, adhesion, and invasion. Previous studies have found that ANO1 can inhibit the growth and invasion of ovarian cancer by blocking the PI3K/Akt signaling pathway, which is useful in prognosis analysis.…”

“…Based on the description provided in the methods section, we constructed the PPI network of the top three modules (gold, steel blue, and turquoise) in terms of the number of genes (Figure 9A-C). PPI-gold contains 94 nodes (42 upregulated The Hub nodes with higher level rankings were PPI-gold: KNG1 (21), GNG4 (19), F2 (15); PPI-steel blue: POSTN (8), THBS2 ( 7), SPP1 (6); and PPI-turquoise: FGA (7). These genes frequently interact with other proteins in each module and are important nodes in the network.…”

“…Ano1, also known as TMEM16A, TAOS2, ORAOV2, and FLJ10261 (DOG1, discovered on GIST-1), encodes a hypothetical protein and belongs to the calcium-activated chloride channels family. [6][7][8][9] Studies have found Ano1 is expressed in exocrine glands, nervous system, smooth muscles, and other tissues. 10,11 As a transmembrane protein, Ano1 is involved in a variety of biological functions, such as cell proliferation, attachment, and movement.…”

Mucin 5AC expression is common but unrelated to tumor progression in pancreatic adenocarcinoma

“…In this retrospective study, the TMA was constructed as previously described by Kononen et al 16 The TMA included 532 primary pancreatic cancers, 61 primary adenocarcinomas of the ampulla Vateri, and 6 primary pancreatic acinar cell carcinomas from the Institute of Pathology of the University Medical Center Hamburg-Eppendorf (Table 1). 17 The tumor samples were consecutively collected from patients who underwent different types of pancreatectomy at the Department of General- Visceral- and Thoracic-Surgery, University Medical Center Hamburg-Eppendorf between 1993 and 2005, and were selected for sufficient amounts of cancer cells in the paraffin block. A single 0.6 mm core per tumor was sampled for TMA construction.…”

DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis

“…This approach allows direct delivery of highly potent cytotoxic agents to antigen-positive tumor tissue with limited off-target toxicities (19). Since the first ADC, Mylotarg ® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA) against CD33-positive acute myeloid leukemia (AML), there have been 14 ADCs received market approval (20,21), and over 100 ADCs are currently under clinical development. However, half of these 14 ADCs approved by FDA are mainly used against hematological malignancies such as AML and anaplastic large cell lymphoma (ALCL).…”