J Cancer 2021; 12(2):316-325. doi:10.7150/jca.47577

Research Paper

TRIM37 contributes to malignant outcomes and CDDP resistance in gastric cancer

Keiji Nishibeppu1*, Shuhei Komatsu1✉*, Jun Kiuchi1, Takuma Kishimoto1, Yusuke Takashima1, Katsutoshi Shoda1, Tomohiro Arita1, Toshiyuki Kosuga1, Hirotaka Konishi1, Atsushi Shiozaki1, Takeshi Kubota1, Kazuma Okamoto1, Hitoshi Fujiwara1, Hitoshi Tsuda2,3, Eigo Otsuji1

1. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan.
2. Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.
3. Department of Basic Pathology, National Defense Medical College, Tokorozawa, Japan.
*These authors contributed equally to this work.

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Citation:
Nishibeppu K, Komatsu S, Kiuchi J, Kishimoto T, Takashima Y, Shoda K, Arita T, Kosuga T, Konishi H, Shiozaki A, Kubota T, Okamoto K, Fujiwara H, Tsuda H, Otsuji E. TRIM37 contributes to malignant outcomes and CDDP resistance in gastric cancer. J Cancer 2021; 12(2):316-325. doi:10.7150/jca.47577. Available from https://www.jcancer.org/v12p0316.htm

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Abstract

Background: TRIM37 (Tripartite Motif Containing 37) is an E3 ubiquitin ligase for histone H2A and inhibits transcription in several genes. However, it is not known whether it plays a role in gastric cancer (GC). In this study, we tested whether TRIM37 acts as a cancer-promoting factor by being overexpressed in GC.

Methods: We analyzed GC cell lines and 124 primary tumors, which were curatively resected in our hospital between 2001 and 2003.

Results: Overexpression of the TRIM37 protein was detected in almost all GC cell lines and GC samples (76 out of 124 cases) and was significantly correlated with lymphatic and venous invasion, advanced T-Stage, N-Stage, histology and high recurrence rate. Patients with TRIM37 overexpressing tumors had a worse survival rate than those with non-expressing tumors (P=0.0057). Moreover, TRIM37 positivity was identified as an independent factor predicting worse outcomes (P=0.018, Hazard ratio 3.41). The apoptotic cell analysis showed that the knockdown of TRIM37 increased apoptosis in comparison with the control. In TRIM37 overexpressing GC cells, knockdown of TRIM37 suppressed the migration and invasion.

Conclusions: TRIM37 plays a crucial role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.

Keywords: TRIM37, prognosis, proliferation, chemoresistance, gastric cancer