Abstract
Purpose TRPM7 is known to play a key role in tumor progression by regulating cellular proliferation, migration, and invasion in various cancer cell lines. However, there are no comprehensive clinical studies about the effect of TRPM7 expression on gastric cancer (GC) prognosis. In this study, it was aimed at investigating the effect of TRPM7 expression on prognosis in GC patients. Additionally, for the first time, it was investigated whether the density of Factor XIIIa-expressing tumor-associated macrophages (TAMs) in GC has an effect on the biological behaviour of the tumor. Methods TRPM7 expression and Factor XIIIa-expressing TAM density were immunohistochemically evaluated in paraffin-embedded tumor tissues of 204 GC patients undergoing surgery at a single institution. Results Tumor size was clearly higher in cases with high TRPM7 expression than those with low expression (p < 0.001, Mann-Whitney U). TRPM7 overexpression was closely related to high depth of tumor invasion (p < 0.001, ANOVA), increased lymph node metastasis (p < 0.001, ANOVA), and high distant metastasis rate (p < 0.001, Mann-Whitney U). These findings exposed that high TRPM7 expression is effective in the progression and aggressiveness of GC. In addition, while high CD8+ TIL density affects the prognosis positively, it was determined that high Factor XIIIa+ TAM density negatively affects the prognosis of patients with GC. Furthermore, multivariate analyses revealed TRPM7 overexpression was independently related with short overall (HR 9.64, 95% CI 5.74–16.19, p < 0.001) and disease-free survival (HR 5.67, 95% CI 3.61-8.92, p < 0.001) in GC patients. Conclusions Our data suggest that high TRPM7 expression is closely related to progressive tumor behaviour in GC and independently negatively affects survival in patients. In addition, it was determined that a high density of Factor XIIIa+ TAMs negatively affects the prognosis of patients with GC.
Highlights
Gastric cancer (GC), the fifth most common cancer worldwide and the third leading cause of cancer-related death, remains a major public health problem [1,2,3]
The primary aim of the present study is to investigate the prognostic value of TRPM7 expression in GC patients
High TRPM7 expression is closely related to aggressive tumor behaviour and advanced TNM stage
Summary
Gastric cancer (GC), the fifth most common cancer worldwide and the third leading cause of cancer-related death, remains a major public health problem [1,2,3]. Evidence revealing in recent years indicates that ion channels both regulate ion levels in cells, membrane potential, and intercellular signalling and play significant roles in cell proliferation, migration, apoptosis, and differentiation [5]. TRPM7 is a featured member of the TRPM family and has managed to attract the attention of cancer researchers in recent years [7]. Preliminary studies have demonstrated that in addition to its physiological functions, TRPM7 may play a key role in cancer by regulating cellular proliferation, migration, and invasion in cancer cell lines [8, 9]. Kim et al suggested TRPM7 is overexpressed in several GC cell lines, including AGS which is one of the most common human gastric adenocarcinoma cell lines [10]. In some studies using a variety of Gastroenterology Research and Practice
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