Reduced Expression of ZDHHC2 Is Associated with Lymph Node Metastasis and Poor Prognosis in Gastric Adenocarcinoma

Abstract

BackgroundZinc finger, DHHC-type containing 2 (ZDHHC2), originally named as reduced expression associated with metastasis protein (REAM), has been proposed as a putative tumor/metastasis suppressor gene and is often aberrantly decreased in human cancers. However ZDHHC2 expression pattern and its clinical significance have not yet been investigated in gastric adenocarcinoma.Methodology/Principal FindingsQuantitative Real-Time PCR (qRT-PCR) and immunostaining were performed to detect ZDHHC2 expression in gastric adenocarcinoma, and then the correlation between ZDHHC2 expression and clinicpathologic parameters, and patient survival was analyzed. Compared to the adjacent normal tissues, ZDHHC2 expression was significantly reduced in gastric tumor tissues as shown by qRT-PCR and immunostaining. Low expression of ZDHHC2 was observed in 44.7% (211/472) of gastric adenocarcinoma patients, and was associated significantly with lymph node metastasis (p<0.001) and histological grade (p<0.001). Multivariate Cox regression analysis indicated that ZDHHC2 expression had a significant, independent predictive value for survival of gastric cancer patients (HR = 0.627, p = 0.001).Conclusions/SignificanceOur data suggest that reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.

Correlated S-palmitoylation profiling of Snail-induced epithelial to mesenchymal transition

“…There are several potential mechanisms supporting this phenomenon, including Snail-dependent reduction in DHHC protein acyl transferase activity, increased expression or activity of acyl protein thioesterases, or reduction in palmitoyl-CoA levels. Several DHHC enzymes are reported to safeguard cells from malignancy, including DHHC2, DHHC14, and DHHC17 37–39 , altering the membrane organization and localization of key signaling proteins. This repression is unlikely due to redox regulation of DHHC activity, since we report Snail expression leads to a broad induction of antioxidant enzymes.…”

A Critical Role for ZDHHC2 in Metastasis and Recurrence in Human Hepatocellular Carcinoma

“…It was reported that reduced ZDHHC2 expression is observed in gastric adenocarcinoma patients and associated with lymph node metastasis and independently predicts an unfavorable prognosis [28]. However, the expression level of ZDHHC2 in HCC remains to be explored.…”

Synthetic protein lipidation

“…DHHC5 seems to have an oncogenic role that is dependent on its catalytic activity, contributing to tumor formation in NSCLC [40]. On the other hand, DHHC2 plays a putative tumor suppressor role as indicated by its reduced expression in gastric tumor tissues, which is associated with lymph node metastasis [41].…”