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Tumor Biology

, Volume 33, Issue 6, pp 1845–1854 | Cite as

Aberrant SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas

  • Xiao-yan Xu
  • Wen-feng Gou
  • Xue Yang
  • Guo-li Wang
  • Hiroyuki Takahashi
  • Miao Yu
  • Xiao-yun Mao
  • Yasuo Takano
  • Hua-chuan Zheng
Research Article

Summary

Sarco (endo)plasmic reticulum Ca2+-ATPase (SERCAs) 3 is involved in calcium mobilization from endoplasmic reticulum into cytosol and closely links to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding, and carcinogenesis. To clarify the role of SERCA3 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa (NNM), and metastatic lymph node. SERCA3 expression was studied in gastric carcinoma tissue and cell lines by Western blot, reverse transcriptase-polymerase chain reaction, or immunofluorescence. The results demonstrated that SERCA3 was distinctively expressed in GES-1, AGS, BGC-823, GT-3TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, and STKM-2 at both mRNA and protein levels. The carcinomas showed higher SERCA3 mRNA expression than the matched NNM by real-time PCR and ISH (P < 0.05). Immunohistochemically, SERCA3 expression was decreased from gastric NNM, primary to metastatic carcinoma (P < 0.05). SERCA3 expression was negatively related to depth of invasion, distant metastasis, and tumor node metastasis (TNM) staging (P < 0.05), but not to age, sex, lymphatic or venous invasion, or lymph node metastasis (P > 0.05). Kaplan–Meier analysis indicated that SERCA3 expression was positively associated with favorable prognosis of the patients with gastric carcinoma (P < 0.05). Cox’s proportional hazard model indicated that venous invasion, distant metastasis and TNM staging (P < 0.05) were independent prognostic factors for gastric carcinomas. It was suggested that downregulated SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas. It might be employed to indicate the pathobiological behaviors and prognosis of gastric carcinomas.

Keywords

Gastric carcinoma SERCA3 Pathogenesis Progression Prognosis 

Notes

Acknowledgments

This study was supported by Shenyang Outstanding Talent Foundation of China; Shenyang Science and Technology grant (F11-264-1-10); Natural Scientific Foundation of China (no. 81001093, no. 81101886, no. 81172371); a Project Supported by Scientific Research Fund of Liaoning Provincial Education Department (L2010649); Specialized Research Fund for the Doctoral Program of Higher Education (no. 20102104120026) and Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports and Technology of Japan (23659958).

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Xiao-yan Xu
    • 1
  • Wen-feng Gou
    • 2
  • Xue Yang
    • 2
  • Guo-li Wang
    • 2
  • Hiroyuki Takahashi
    • 3
  • Miao Yu
    • 4
  • Xiao-yun Mao
    • 4
  • Yasuo Takano
    • 3
  • Hua-chuan Zheng
    • 2
  1. 1.Department of Pathophysiology, Institute of Pathology and Pathophysiology, College of Basic MedicineChina Medical UniversityShenyangChina
  2. 2.Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic MedicineChina Medical UniversityShenyangChina
  3. 3.Clinical Research InstituteKanagawa Cancer CenterYokohamaJapan
  4. 4.Department of Surgical OncologyThe First Affiliated Hospital of China Medical UniversityShenyangChina

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