Expression of resistin-like molecule beta in gastric cancer: its relationship with clinicopathological parameters and prognosis

Abstract

Resistin-like molecule beta (RELMbeta), an intestinal goblet cell-specific protein, is a biomarker of intestinal metaplasia in Barrett's esophagus and over-expressed in colon cancer. Since gastric adenocarcinomas can arise through a process of intestinalization, we hypothesized that RELMbeta might be aberrantly expressed in gastric cancer. This study was undertaken to examine the RELMbeta expression in gastric cancer and correlate it with clinical outcome. One hundred and thirty-six gastric cancer patients were evaluated for the RELMbeta expression by immunohistochemistry. The RELMbeta transcripts were measured by real-time quantitative PCR. In normal gastric mucosa, RELMbeta expression was absent, whereas areas of intestinal metaplasia revealed RELMbeta reactivity. Eighty-nine patients of gastric cancer (65.4%) were positive for RELMbeta expression. In a subtotal of 20 patients, RELMbeta transcripts were positively correlated with protein levels in gastric cancer tissues, but absent in normal gastric mucosa. The expression rate of RELMbeta was higher in intestinal-type carcinomas than in diffuse-type carcinomas (P < 0.001). RELMbeta positivity in gastric cancer was positively correlated with tumor differentiation (P = 0.001) and inversely correlated with tumor infiltration (P = 0.007), lymph node metastasis (P = 0.035), and heparanase expression (P < 0.001), without correlation with age, gender, tumor location and size, tumor-node metastasis stages, and Ki-67 expression. Patients showing positive RELMbeta expression had a significantly longer overall survival than those with negative expression (P = 0.001). These results provide evidences that the RELMbeta expression in gastric cancer is correlated with clinicopathological features and may be a useful prognostic factor for predicting the outcome of gastric cancer patients.

NF‐κB Signaling in Gastric Cancer

“…Angiogenesis-regulating resistin-like molecule-α (RELM-α) is overexpressed in gastric tumors and associates with advanced stage and tumor size [110]. The silencing of RELM-α expression by Ad5/F35-siRNA treatment significantly inhibited NF-κB activation and attenuated VEGF and MMP-9 expression as well as cell migratory and invasive ability in SGC7901 and MKN45 gastric cancer cells [111].…”

Aberrant expression of intelectin-1 in gastric cancer: its relationship with clinicopathological features and prognosis

“…The intestinal type is characterized by cancer cells that attempt to form glandular structures, while the diVuse type is distinguished by scattered tumor cells that lack cohesive properties and penetrate the stroma (Lauren 1965). Recent studies indicate that some of goblet cell-derived proteins, such as mucin 2 (Lee et al 2007;Pinto-de-Sousa et al 2002), intestinal trefoil factor (Katoh 2003;Kirikoshi and Katoh 2002), and resistin-like molecule beta (Zheng et al 2010), can be served as biomarkers for intestinal metaplasia and are over-expressed in both histological types (intestinal and diVuse) of gastric cancer. Therefore, it has been a research focus to further elucidate the diagnostic and prognostic values of goblet cell-derived proteins in the progression of gastric cancer.…”

Human resistin and the RELM of Inflammation in diabesity

“…In vitro overexpression of RELMβ abolished invasion, metastasis and angiogenesis of gastric cancer cells [ 92 ]. Several studies analyzing RELMβ in colon cancer have positively correlated the expression of RELMβ with tumor progression [ 93 , 94 ]. Patients with RELMβ expression were shown to have a significantly longer survival rate than those with negative RELMβ expression [ 94 ].…”