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Increased Expression of DNAJC12 is Associated with Aggressive Phenotype of Gastric Cancer

Yasuo Uno MD, Mitsuro Kanda MD, PhD, FACS, Takashi Miwa MD, Shinichi Umeda MD, Haruyoshi Tanaka MD, Chie Tanaka MD, PhD, Daisuke Kobayashi MD, PhD, Masaya Suenaga MD, PhD, Norifumi Hattori MD, PhD, Masamichi Hayashi MD, PhD, Suguru Yamada MD, PhD, FACS, Goro Nakayama MD, PhD, Michitaka Fujiwara MD, PhD, Yasuhiro Kodera MD, PhD, FACS
Gastrointestinal Oncology
Volume 26, Issue 3 / March , 2019

Abstract

Background

Identification of gastric cancer-related molecules is necessary to elucidate the pathological mechanisms of this heterogeneous disease. The purpose of this study was to identify novel genes associated with aggressive phenotypes of gastric cancer.

Methods

Global expression profiling was conducted using tissues from four patients with metastatic gastric cancer to identify genes overexpressed in gastric cancer. Fifteen gastric cell lines and 262 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. The contribution of the candidate gene on gastric cancer cell proliferation, invasion, adhesion, and migration were evaluated using small interfering RNA.

Results

DnaJ heat shock protein family (Hsp40) member C12 (DNAJC12) was identified as a candidate gene by transcriptome analysis. In clinical samples, DNAJC12 mRNA levels were higher in gastric cancer tissues compared with normal adjacent tissues. Patients with high DNAJC12 expression showed significantly shorter overall survival in our cohort and in the extra-validation cohort analyzed by a published microarray dataset. High DNAJC12 expression in gastric cancer tissues was significantly associated with lymphatic involvement, infiltrative growth type, lymph node metastasis, and advanced stage and was identified as an independent prognostic factor for overall survival in multivariable analysis. Increased expression of DNAJC12 was found in 12 of 14 examined gastric cancer cell lines. Knockdown of DNAJC12 expression significantly decreased the proliferation and invasion abilities of gastric cancer cells.

Conclusions

Our findings support DNAJC12 as a candidate gene associated with aggressive phenotypes of gastric cancer.

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