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J Cancer 2018; 9(19):3540-3547. doi:10.7150/jca.26293 This issue Cite

Research Paper

Prognostic Stratification of Advanced Gastric Signet Ring Cell Carcinoma by Clinicopathological Factors and GALNT14 Genotype

Tsung-Hsing Chen^1,2, Wey-Ran Lin^1,5✉, Chieh Lee³, Cheng-Tang Chiu¹, Jun-Te Hsu ⁴, Ta-Sen Yeh⁴, Kwang-Huei Lin^5,6,7, Puo-Hsien Le¹, Chau-Ting Yeh^1,5✉

1. Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
2. Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
3. Department of Industrial Engineering & Management, Yuan Ze University College of Engineering, Chung-Li City, Taiwan
4. Department of Surgery, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
5. Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
6. Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
7. Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology Taoyuan, Taiwan

✉ Corresponding authors: Chau-Ting Yeh, MD, PhD, Director, Liver Research Center, Linkou Chang Gung Memorial Hospital, 5, Fu-Shin St., Kuei-Shan District, Taoyuan, Taiwan. E-mail address: chautingycom and Wey-Ran Lin, MD, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, 5, Fu-Shin St., Kuei-Shan District, Taoyuan, Taiwan. Email address: victor.wr.lincom More

Abstract

Background: Gastric signet ring cell carcinoma (SRCC) is a histologic variant characterized by abundant intracytoplasmic mucin. Although it has been recognized that gastric adenocarcinoma harboring this feature has poorer prognosis, prognostic stratification within gastric SRCCs themselves has not been clearly defined. N-acetylgalactosaminyltransferase14 (GALNT14) genotype has been associated to poorer treatment outcome in mucinous type colorectal cancer. Here we incorporated clinicopathological factors and GALNT14 genotype to stratify prognosis of advanced gastric SRCC.

Methods: Totally 347 gastric SRCC patients were retrospectively enrolled for GALNT14 genotyping. Clinicopathological factors were included for prognosis stratification.

Results: Of the 347 patients, 341 underwent radical-intent gastrectomy and 6 received palliative gastrectomy. Kaplan-Meier analysis for overall survival indicated that Tumor-Node-Metastasis staging could only stratify the patients into three prognosis-distinguishable groups: group-1 (stage IA); group-2 (stage IB/IIA) and group-3 (the remaining Tumor-Node-Metastasis stages combined). Multivariate Cox-proportional hazard models for group-3 patients revealed GALNT14 “TT” genotype (P = 0.0482). Tumor size (P = 0.0009), node status (P <0.0001), metastasis status (P = 0.0096), and perineural invasion (P = 0.037) independently associated with unfavorable OS. Exploratory subgroup analysis showed that GALNT14”TT” genotype was associated with unfavorable OS in SRCCs with more aggressive phenotypes: node status >0 (P = 0.0013), lymphatic invasion (P = 0.021), vascular invasion (P = 0.0076) and perineural invasion (P = 0.0161). Accordingly, a scoring system was established capable of stratifying advanced gastric SRCC patients into three distinguishable prognostic subgroups.

Conclusions: Gastric SRCC could be stratified into different prognostic subgroups by combining clinicopathological factors and GALNT14 genotype.

Keywords: GALNT14, signet ring cell, lymphatic invasion, vascular invasion, perineural invasion

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