Abstract
Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancer-related deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffuse-type gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (IFNGR2), IQ motif containing E (IQCE), transient receptor potential cation channel subfamily M member 4 (TRPM4), and structure-specific endonuclease subunit SLX4 (SLX4) were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.
Highlights
In the year 2018, gastric cancer had the fifth-highest incidence rate and was the third leading cause of cancer-related deaths worldwide [1]
SNU-484 male diffuse gastric cancer cells showed no difference in tumor growth between male and female xenograft models (Supplementary Figure S1B)
We investigated the effect of endogenous and exogenous estrogen on diffuse-type gastric cancer xenograft models
Summary
In the year 2018, gastric cancer had the fifth-highest incidence rate and was the third leading cause of cancer-related deaths worldwide [1]. Many researchers are closely investigating the characteristics of gastric cancer cells to identify potential biomarkers for enhanced diagnostic and therapeutic approaches. Gastric cancer incidence and mortality rates seem to differ markedly based on sex [1]. Studies that consider sex-based differences in gastric cancer are rare; in vivo systems such as xenograft mouse models provide a convenient approach to study these sexbased differences. The incidence or prognosis varies depending on the type of gastric cancer. Gastric adenocarcinomas were divided into four subtypes as follows: tumors positive for Epstein-Barr virus (EBV), microsatellite unstable tumors (MSI), genomically stable
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