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Annals of Surgical Oncology

, Volume 26, Issue 3, pp 836–844 | Cite as

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

  • Yasuo Uno
  • Mitsuro KandaEmail author
  • Takashi Miwa
  • Shinichi Umeda
  • Haruyoshi Tanaka
  • Chie Tanaka
  • Daisuke Kobayashi
  • Masaya Suenaga
  • Norifumi Hattori
  • Masamichi Hayashi
  • Suguru Yamada
  • Goro Nakayama
  • Michitaka Fujiwara
  • Yasuhiro Kodera
Gastrointestinal Oncology

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.

Notes

Disclosures

None.

Supplementary material

10434_2018_7149_MOESM1_ESM.doc (44 kb)
Supplementary material 1 (DOC 43 kb)
10434_2018_7149_MOESM2_ESM.docx (21 kb)
Supplementary material 2 (DOCX 21 kb)
10434_2018_7149_MOESM3_ESM.doc (52 kb)
Supplementary material 3 (DOC 51 kb)
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Supplementary Fig. 1 (a) Expression analyses of DNAJC12 in clinical samples from 262 gastric cancer patients. ROC curve analysis revealed that the AUC value of DNAJC12 levels was 0.606 for detection of mortality of recurrence, and the optimal cutoff value was 0.00925. (b) Expression analysis of DNAJC12 in gastric cancer cell lines. DNAJC12 mRNA levels were detected in differentiated and undifferentiated gastric cancer cell lines and the control FHs74 epithelial cell line (TIFF 6033 kb)

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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Yasuo Uno
    • 1
  • Mitsuro Kanda
    • 1
    Email author
  • Takashi Miwa
    • 1
  • Shinichi Umeda
    • 1
  • Haruyoshi Tanaka
    • 1
  • Chie Tanaka
    • 1
  • Daisuke Kobayashi
    • 1
  • Masaya Suenaga
    • 1
  • Norifumi Hattori
    • 1
  • Masamichi Hayashi
    • 1
  • Suguru Yamada
    • 1
  • Goro Nakayama
    • 1
  • Michitaka Fujiwara
    • 1
  • Yasuhiro Kodera
    • 1
  1. 1.Department of Gastroenterological Surgery (Surgery II)Nagoya University Graduate School of MedicineNagoyaJapan

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