Ornithine decarboxylase and glutamate decarboxylase 65 as prognostic markers of gallbladder malignancy: A clinicopathological study in benign and malignant lesions of the gallbladder

Abstract

Abstract. Ornithine decarboxylase (ODC) plays a critical role in cell proliferation and is overexpressed in a variety of cancers. Furthermore, γ-aminobutyric acid (GABA) content and glutamate decarboxylase (GAD) activity are increased in neoplastic tissues in colon and breast cancer. However, few studies have examined these molecules in gallbladder cancer specimens. We observed the expression levels of ODC and GAD65 in benign and malignant lesions of the gallbladder and investigated their clinicopathological significance for the first time. The expression levels of ODC and GAD65 in specimens from gallbladder adenocarcinoma (n=108), peritumoral tissues (n=46), adenomatous polyps (n=15) and chronic cholecystitis (n=35) were detected using immunohistochemical methods. Kaplan-Meier survival and Cox regression analyses were carried out to explore the clinical and pathological correlations. The levels of positive staining of ODC and GAD65 were significantly higher in gallbladder adenocarcinoma than in peritumoral tissues, adenomatous polyps and chronic cholecystitis. The Kaplan-Meier survival analysis and Cox regression analysis showed that the expression of ODC and GAD65 correlated significantly with the one-year survival rate and the mean survival time of the patients postoperatively. We conclude that the overexpression of ODC and GAD65 are significant in the carcinogenesis and progression of gallbladder adenocarcinoma. They may be important biological markers for the evaluation of biological behaviors and the prognosis of gallbladder adenocarcinoma.

Small Cell Lung Cancer Expressing Glutamate Decarboxylase with Latent Autoimmune Diabetes in Adults

“…In a clinicopathological study of benign and malignant lesions in the gallbladder, the expression level of GAD65 was significantly higher in the gallbladder adenocarcinoma than in the peritumoral tissues, adenomatous polyps, or areas of chronic cholecystitis. Increased GAD65 expression is a poor prognostic factor for both 1-year survival rates and mean survival times after surgery in patients with cholecystic cancer (10). Similar findings have also been reported in colon (11), breast (12), and prostate cancers (13).…”

Association between the ornithine decarboxylase G316A polymorphism and breast cancer survival

“…However, the application of these compounds in a clinical setting is limited due to their poorly-tolerated adverse reactions (24,25). Ornithine decarboxylase (ODC) is the most significant and rate-limiting enzyme in the pathway of polyamine synthesis, which is critical in cell proliferation and highly expressed in a variety of cancer types, including breast cancer (6,(26)(27)(28). Previous studies have indicated that the overexpression of ODC is common in carcinogenesis and cancer progression (6,(26)(27)(28).…”

“…Previous studies have indicated that the overexpression of ODC is common in carcinogenesis and cancer progression (6,(26)(27)(28). Therefore, certain studies have proposed that it may be an important biological marker in the evaluation of biological behavior and the prognosis of various types of cancer (13,26). Recently, an increasing number of studies have focused on ODC as a potential target for cancer therapy (24,25).…”

“…Ornithine decarboxylase (ODC) is the most significant and rate-limiting enzyme in the pathway of polyamine synthesis, which is critical in cell proliferation and highly expressed in a variety of cancer types, including breast cancer (6,(26)(27)(28). Previous studies have indicated that the overexpression of ODC is common in carcinogenesis and cancer progression (6,(26)(27)(28). Therefore, certain studies have proposed that it may be an important biological marker in the evaluation of biological behavior and the prognosis of various types of cancer (13,26).…”

The role of glutamate decarboxylase 65 in gastric cancer development, progression, and prognosis

“…The discovery and application of biomarkers that could be utilized in conjunction with traditional cancer diagnosis, staging and prognosis could potentially help to improve early diagnosis and patient care . An increased GABA content and high GAD activity have been observed in non‐small‐cell lung cancer, pancreatic cancer, colon cancer, brain tumours, breast cancer, prostate cancer, and gallbladder cancer . However, the majority of these studies explored the role of GABA.…”