Expression profiling of CPS1 in Correa's cascade and its association with gastric cancer prognosis

Fang,Xuqian; Wu,Xiaoqiong; Xiang,Enfei; Luo,Fangxiu; Li,Qinqin; Ma,Qianchen; Yuan,Fei; Chen,Peizhan

doi:10.3892/ol.2021.12702

Expression profiling of CPS1 in Correa's cascade and its association with gastric cancer prognosis

Authors:
- Xuqian Fang
- Xiaoqiong Wu
- Enfei Xiang
- Fangxiu Luo
- Qinqin Li
- Qianchen Ma
- Fei Yuan
- Peizhan Chen
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Affiliations: Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201821, P.R. China, Department of Clinical Laboratory, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201821, P.R. China, Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201821, P.R. China
Published online on: April 2, 2021 https://doi.org/10.3892/ol.2021.12702
Article Number: 441
Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Carbamoyl phosphate synthetase 1 (CPS1), which is the antigen for the hepatocyte paraffin 1 antibody, exhibits focal immunoreactivity in adenocarcinoma from the gastrointestinal tract, but its expression profiles and roles in gastric cancer (GC) remain largely unknown. The present study aimed to determine the expression pattern and prognostic value of CPS1 in Correa's cascade using tissues from 32 patients with chronic atrophic gastritis with intestinal metaplasia (IM), 62 patients with low‑ or high‑grade intraepithelial neoplasia (IN) and 401 patients with GC. The expression of CPS1 was diffuse and strongly positive in 32 cases (100%) of IM of the glandular epithelium, and gradually downregulated in Correa's cascade, with a strongly positive ratio of 21 (70%) in low‑grade IN and 4 (12.5%) in high‑grade IN. The levels of CPS1 expression were significantly higher in diffuse‑type GC, with 37 (26%) cases strongly positive for CPS1, compared with 14 (8%) in intestinal‑type and 11 (13%) cases in mixed‑type GC. In intestinal‑type GC, CPS1 expression was completely lost in 107 (62%) of cases, which was associated with an advanced Tumor‑Node‑Metastasis stage (P=0.031) and depth of invasion (P=0.037). Kaplan‑Meier analysis suggested that low CPS1 expression levels were independently associated with a short overall survival (OS) time in the three types of GC (P<0.001 in intestinal‑type, P=0.003 in diffuse‑type and P=0.018 in mixed‑type GC). Furthermore, low levels of CPS1 mRNA and high methylation levels in the CPS1 promoter were associated with a short OS time in patients with GC. These results suggested that the expression of CPS1 was progressively downregulated in Correa's cascade, and that CPS1 may serve as a prognostic marker for patients with GC, regardless of tumor type.

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