Clinical Research Papers:
TOP2A, GGH, and PECAM1 are associated with hematogenous, lymph node, and peritoneal recurrence in stage II/III gastric cancer patients enrolled in the ACTS-GC study
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 2332 views | HTML 2418 views | ?
Abstract
Masanori Terashima1,*, Wataru Ichikawa2,*, Atsushi Ochiai3, Koji Kitada4, Issei Kurahashi5, Shinichi Sakuramoto6, Hitoshi Katai7, Takeshi Sano8, Hiroshi Imamura9, and Mitsuru Sasako10; for the ACTS-GC Group
1 Division of Gastric Surgery, Shizuoka Cancer Center, Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan
2 Division of Medical Oncology, Showa University Fujigaoka Hospital, Kanagawa, Japan
3 Division of Pathology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba, Japan
4 Department of Surgery, National Hospital Organization Fukuyama Medical Center, Okinogami-cho, Fukuyama, Hiroshima, Japan
5 Data Innovation Center, iAnalysis LLC, Minamiaoyama, Minato-ku, Tokyo, Japan
6 Department of Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka, Saitama, Japan
7 Gastric Surgery Division, National Cancer Center Hospital, Tsukiji, Chuo, Tokyo, Japan
8 Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Koto-Ku, Tokyo, Japan
9 Department of Surgery, Toyonaka Municipal Hospital, Shibahara-cho, Toyonaka, Osaka, Japan
10 Department of Surgery, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan
* These authors have contributed equally to this work
Correspondence to:
Masanori Terashima, email:
Keywords: stomach neoplasm, DNA topoisomerase II alpha, gamma-glutamyl hydrolase, CD31
Received: September 24, 2016 Accepted: February 12, 2017 Published: March 04, 2017
Abstract
Background: To identify factors related to relapse sites, we carried out an exploratory biomarker analysis of data from the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer study, which is a randomized, controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer.
Patients and Methods: Surgical specimens from 829 patients were retrospectively examined, and 63 genes involved in a variety of biological processes were analyzed by quantitative real-time PCR. Gene expression normalized to reference genes was categorized as lower or higher than the median, and association with relapse sites was analyzed based on 5-year relapse-free survival.
Results: Hematogenous, lymph node, and peritoneal recurrence developed in 72, 105, and 138 of the 829 patients, respectively; hazard ratios were 0.79 (95% confidential interval: 0.54–1.16), 0.51 (0.31–0.82), and 0.60 (0.42–0.84), respectively. Expression of platelet/endothelial cell adhesion molecule 1 (PECAM1) and topoisomerase II alpha (TOP2A) was strongly correlated with hematogenous recurrence and peritoneal recurrence, respectively (false discovery rate = 7.7×10-5 and 0.002, respectively). Gamma-glutamyl hydrolase (GGH) expression was moderately correlated with lymph node recurrence (false discovery rate = 0.34). Relapse-free survival was worse in patients expressing high levels of PECAM1 (hazard ratio = 2.37, 1.65–3.41), TOP2A (hazard ratio = 2.35, 1.55–3.57), or GGH (hazard ratio = 1.87, 1.13–3.08), respectively. A multivariate analysis revealed that these were stronger independent risk factors than tumor histological type.
Conclusion: In patients with stage II/III gastric cancer, TOP2A, GGH, and PECAM1 levels in primary tumors are linked to high risk of hematogenous, lymph node, and peritoneal recurrence, respectively.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 15895