Impact of the ESM-1 Gene Expression on Outcomes in Stage II/III Gastric Cancer Patients Who Received Adjuvant S-1 Chemotherapy

Abstract

Background/Aim: Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. Patients and Methods: The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. Results: A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). Conclusion: ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. Gastric cancer is the fifth most major cancer among new cases and the third most common cause of cancer-associated mortality worldwide, numbering 1,033,701 and 781,631 in 2018, respectively (1). The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that adjuvant S-1 chemotherapy significantly improved the survival of patients who received D2 gastrectomy for pathological stage (pStage) II/III gastric cancer (2, 3). Furthermore, in the CLASSIC trial and JACCRO-07 trial, the effectiveness of capecitabine plus oxaliplatin therapy for pStage II/III gastric cancer and S-1 plus docetaxel therapy for pStage III was confirmed (4-6). Thus, fluoropyrimidine remains the key drug for adjuvant chemotherapy in gastric cancer patients (7). Endothelial cell-specific molecule-1 (ESM-1) was originally cloned from a human endothelial cell cDNA 461 This article is freely accessible online.

Endothelial-Specific Molecule 1 Inhibition Lessens Productive Angiogenesis and Tumor Metastasis to Overcome Bevacizumab Resistance

“…ESM1 is highly expressed in vascular endothelial cells, i.e., epithelial cells of the distal renal tubules, bronchial tubes, and submucosal lung glands in normal tissues [ 22 ]. ESM1 expression is also upregulated in lung cancer [ 23 ], gastric cancer [ 24 ], breast cancer [ 25 ], bladder cancer [ 26 ], and other malignant tumors and is associated with the inflammatory response and tumor progression. Moreover, ESM1 participates in tumor growth, migration, invasion, and angiogenesis [ 27 ].…”

Endothelial cell-specific molecule 1 drives cervical cancer progression

“…Recent studies have reported that ESM1 is expressed in multiple tissues, including the kidney, liver, thyroid gland, skin, and gastrointestinal tract [14][15][16]. Moreover, aberrant ESM1 expression is associated with multiple diseases, including inflammation [17], vascular disorders [18], and cancer [19].ESM1 is upregulated in a broad spectrum of cancers, often correlated with a poor prognosis [19][20][21][22].…”

Screening diagnostic markers for acute myeloid leukemia based on bioinformatics analysis

“…Studies have shown that ESM1 can be used as a prognostic marker in triple-negative breast cancer ( 21 , 26 ). It may be that ESM1 promotes tumor invasion and migration by regulating tumor angiogenesis ( 27 ).…”