Identification of AQP3 and CD24 as biomarkers for carcinogenesis of gastric intestinal metaplasia

Abstract

Gastric intestinal metaplasia (GIM) is a precancerous gastric carcinoma (GC) lesion with pivotal roles in carcinogenesis. CD24, LGR5 and Ki67 are expressed in GIM; we previously demonstrated that aquaporin 3 (AQP3) is expressed in goblet cells and is positively correlated with GIM severity. However, the relationships of AQP3 with GIM classification and with other proteins, and their roles in the transition from GIM to gastric carcinoma (GC) remain unknown. Sixteen patients with intestinal-type GC were enrolled in this study. GIM was determined according to the updated Sydney system; GIM classification was determined via HID-AB staining, and AQP3, CD24, LGR5 and Ki67 expression were determined by immunohistochemistry. Type III GIM was more prevalent around the GC and displayed a positive association with GIM severity. CD24 was found in GIM, but LGR5 and Ki67 were found in tissues regardless of GIM. AQP3 expression showed significant correlation to type III GIM. CD24 expression was correlated with the marked GIM and incomplete GIM, while LGR5 expression decreased with GIM aggravation and did not have relationship with classification of GIM. However, Ki67 presented no association with GIM grade or classification. These observations identify AQP3 and CD24 as biomarkers for carcinogenesis of GIM, and may provide a precise strategy for screening at-risk candidates with GIM.

Alteration and dysfunction of ion channels/transporters in a hypoxic microenvironment results in the development and progression of gastric cancer

“…A previous study showed that AQP3 is expressed in goblet cells and is positively correlated with gastric intestinal metaplasia (GIM) severity [45]. In addition, it has been found that AQP3 is highly expressed in GC tissues and regulates the proliferation, migration and invasion of human GC cells through a variety of signaling pathways [42].…”

Discovery of plasma messenger RNA as novel biomarker for gastric cancer identified through bioinformatics analysis and clinical validation

“…Gastric cancer (GC) is one of the most common diagnosed cancers worldwide and the third leading cause of cancer-related mortality after lung and liver cancer (Ferlay et al, 2015). The carcinogenesis and progression of GC is complex, involving the alternations of multi-step and multi-genes (Zhao et al, 2017). The 5-year survival rate of GC diagnosed at a later stage is less than 20%, but rises to 90% for patients diagnosed at an early stage (Stahl et al, 2017).…”

Inhibition of aquaporin-3 in macrophages by a monoclonal antibody as potential therapy for liver injury

“…There is increasing evidence from AQP3 −/− mice and AQP3-knockdown cells for the involvement of AQP3 in various inflammatory diseases including atopic dermatitis, psoriasis, allergy, and cancer progression, in which AQP3 transport function supported cell proliferation, migration, and inflammation [22][23][24][25][26]42,57,58 . Also, many descriptive studies have shown positive correlations between AQP3 expression and cancer progression and prognosis [59][60][61][62][63][64][65] . Thus, AQP3 inhibition has been suggested as a potential therapeutic target for a variety of diseases.…”