Expression and Significance of MyD88 in Patients With Gastric Cardia Cancer in a High-Incidence Area of China

Abstract

Background: Gastric cardia cancer (GCC) arises in the area of the stomach adjoining the esophageal-gastric junction and has unique risk factors. It was suggested that the involvement of Helicobacter pylori is associated with GCC from high-risk population. Myeloid differentiation factor 88 (MyD88) is a crucial adaptor molecule in Toll-like signaling pathway recognizing H. pylori. Its role in GCC has not been elucidated yet. In this study, our purpose is to investigate the expression and significance of MyD88 in GCC tissue. Methods: Expression of MyD88 and nuclear factor κB (NF-κB) p105/p50 and infection of H. pylori were detected by immunohistochemistry in gastric cardia tissue. The correlation of MyD88 expression to NF-κB p105/p50 expression, H. pylori infection, and clinicopathologic characteristics in gastric cardia tissue was analyzed. The involvement of MyD88 in patient prognosis was also analyzed. Results: Our data showed that the expression of MyD88 elevated from normal mucosa to inflammation (p = 0.071). The expression of MyD88 was enhanced in GCC tissues by contrast to non-malignant cardia mucosa (p = 0.025). What's more, overexpression of MyD88 was detected in intestinal-type adenocarcinoma with inflammation. Patients with high MyD88 staining revealed a better differentiation (p = 0.02). MyD88 also positively correlated with NF-κB p105/p50 expression (p = 0.012) in cancer tissue. Expression of MyD88 was increased but not significantly in biopsies with H. pylori infection compared with non-infected biopsies. Multivariate analyses revealed lymph node metastasis but not MyD88 expression was an independent predictor for patient survival. Conclusion: These findings provide pathological evidence that upregulating MyD88 and inducing inflammation might be involved in gastric cardia carcinogenesis in high-risk population. MyD88 plays a role in gastric cardia carcinogenesis with NF-κB pathway activation. Higher MyD88 expression is not a major prognostic determinant in GCC, but it may relate to the tumor cell differentiation.

GRB7 plays a promoting role in the progression of gastric cancer

“…It holds great therapeutic value in the development of anti-cancer drugs [ 29 ]. Moreover, the activation of the NF-κB pathway by MyD88 has been found to contribute to the progression of gastric cardia carcinogenesis [ 30 ]. Additionally, a genetic defect in MyD88 has been identified in gastric cancer and may increase the risk of developing this type of cancer [ 31 ].…”

Unveiling the Genomic Landscape of Gastric Cancer Diagnosis, a Snapshot

“…According to the etiological classification the upper part of stomach adjoining the esophagus is called cardia and the mid distal stomach is called the non-cardia [11] and the new classification by WHO on tumors of digestive system [12]. Adeno carcinoma is very often found in cardia where esophagus connects to the stomach, followed by antrum and body of the stomach.…”