High ubiquitin-specific protease 44 expression induces DNA aneuploidy and provides independent prognostic information in gastric cancer

Sho Nishimura, Eiji Oki, Kouji Andou, Makoto Iimori, Yu Nakaji, Yuichiro Nakashima, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39.6%) than in gastric normal mucosa (mean, 14.6%) (P < 0.0001). DNA aneuploidy was observed in 124 gastric cancer cases and high USP44 expression in cancer strongly correlated with DNA aneuploidy (P = 0.0005). The overall survival was significantly poorer in the high USP44 expression group compared with the low USP44 group (P = 0.033). Notably, USP44 expression had no prognostic impact in the diploid subgroup; however, high USP44 expression was a strong poor prognostic factor for progression-free survival (P = 0.018) and overall survival (P = 0.036) in the aneuploid subgroup. We also confirmed that stable overexpression of USP44 induced somatic copy-number aberrations in hTERT-RPE-1 cells (50.6%) in comparison with controls (6.6%) (P < 0.0001). Collectively, our data show USP44 has clinical impact on the induction of DNA aneuploidy and poor prognosis in the CIN gastric cancer subtype.

Original languageEnglish
Pages (from-to)1453-1464
Number of pages12
JournalCancer Medicine
Volume6
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

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Ubiquitin-Specific Proteases
Aneuploidy
Stomach Neoplasms
DNA
Chromosomal Instability
Survival
Gastric Mucosa
Diploidy
Disease-Free Survival
Neoplasms
Chromosomes
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

High ubiquitin-specific protease 44 expression induces DNA aneuploidy and provides independent prognostic information in gastric cancer. / Nishimura, Sho; Oki, Eiji; Andou, Kouji; Iimori, Makoto; Nakaji, Yu; Nakashima, Yuichiro; Saeki, Hiroshi; Oda, Yoshinao; Maehara, Yoshihiko.

In: Cancer Medicine, Vol. 6, No. 6, 01.06.2017, p. 1453-1464.

Research output: Contribution to journalArticle

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abstract = "Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39.6{\%}) than in gastric normal mucosa (mean, 14.6{\%}) (P < 0.0001). DNA aneuploidy was observed in 124 gastric cancer cases and high USP44 expression in cancer strongly correlated with DNA aneuploidy (P = 0.0005). The overall survival was significantly poorer in the high USP44 expression group compared with the low USP44 group (P = 0.033). Notably, USP44 expression had no prognostic impact in the diploid subgroup; however, high USP44 expression was a strong poor prognostic factor for progression-free survival (P = 0.018) and overall survival (P = 0.036) in the aneuploid subgroup. We also confirmed that stable overexpression of USP44 induced somatic copy-number aberrations in hTERT-RPE-1 cells (50.6{\%}) in comparison with controls (6.6{\%}) (P < 0.0001). Collectively, our data show USP44 has clinical impact on the induction of DNA aneuploidy and poor prognosis in the CIN gastric cancer subtype.",
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