HAVCR1 Affects the MEK/ERK Pathway in Gastric Adenocarcinomas and Influences Tumor Progression and Patient Outcome

Ying Li,Hong Jiang,Ji Xue,Jianfeng Yi

doi:10.1155/2019/6746970

Abstract

The hepatitis A virus cellular receptor 1 (HAVCR1) gene as a sensitive and specific biomarker has been reported in various diseases. Especially, HAVCR1 overexpression promotes the development and progression of several human cancers. Hence, we aimed to detect the effects of HAVCR1 on gastric adenocarcinoma (GAC). We first determined the expression of HAVCR1 in GAC tissues compared with normal gastric tissues based on the Cancer Genome Atlas (TCGA) database using bioinformatics analysis methods. Then, we assessed the biological function of HAVCR1 in GAC cells using quantitative real-time reverse transcription-PCR (qRT-PCR), western blot, cell counting kit-8- (CCK-) 8, colony formation assay, wound healing assay, and transwell assay. Our results showed that HAVCR1 expression was upregulated in GAC tissues and positively associated with poor survival. Loss-of-function analyses indicated that knockdown of HAVCR1 inhibited the proliferation, colony formation, migration, and invasion of GAC cells. Furthermore, reduction of HAVCR1 in GAC cells can decrease the expression of phosphorylated MEK/ERK. These findings suggested that HAVCR1 may represent a potential biomarker for GAC prognosis, as well as a novel therapeutic target for GAC treatment.

Highlights

Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality in the world [1]
To identify the potential role of hepatitis A virus cellular receptor 1 (HAVCR1) in gastric adenocarcinoma (GAC), we first assessed HAVCR1 expression in 375 GAC tissues and 32 normal gastric tissues based on The Cancer Genome Atlas (TCGA, https://cancergenome .nih.gov/) database
We found that HAVCR1 expression was obviously upregulated in GAC tissues (n = 375) compared with normal tissues (n = 32; p < 0:01, Figure 1(a))

Summary

Introduction

Gastric cancer is the fourth most common cancer and the second leading cause of cancer mortality in the world [1]. A large majority (approximately 90%) of gastric cancers are gastric adenocarcinomas [1, 2]. A gastric adenocarcinoma (GAC) arises from the glands of the most superficial layer, or the mucosa, of the stomach, which is related with chronic gastritis, high salt intake, Helicobactor pylori infection, smoking, and pernicious anemia [2, 3]. Surgical resection is the standard primary therapy for GAC. To improve the outcome of surgery, adjuvant or neoadjuvant therapy is frequently used in combination with surgery such as radiotherapy and chemotherapy. The addition of radiotherapy and chemotherapy has not been reported to provide any obvious additional benefit [1, 4]. How to treat GAC effectively has become an urgent task. It is critical to choose some effective biomarkers for GAC target therapy

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