Tumor Biology

, Volume 36, Issue 10, pp 7521–7530 | Cite as

Expression of SIP1 is strongly correlated with LDHA and shows a significantly poor outcome in gastric cancer

  • Xuren Sun
  • Zhe Sun
  • Zhi Zhu
  • Chenyan Li
  • Junyan Zhang
  • Huimian Xu
  • Mingjun Sun
Research Article


Smad interacting protein 1 (SIP1) plays an important role in the epithelial-mesenchymal transition (EMT) process by downregulating E-cadherin. Lactate dehydrogenase A (LDHA) is a crucial enzyme that plays an important role in the final step of the Warburg effect by converting pyruvate to lactate irreversibly. EMT and Warburg effect are the hallmarks of advanced gastric cancer progression. Recently, EMT has been thought to be implicated in cancer metabolism. In this study, we want to find whether there was a correlation between the expressions of SIP1 and LDHA in gastric cancer and whether expression of SIP1 alone or in combination with LDHA is associated with the progression of gastric cancer. In the present study, we examined SIP1 and LDHA expression by immunohistochemistry analysis on tissue microarray (TMA) containing tumor tissues and matched non-neoplastic mucosa (NNM). Prognostic value and correlation with other clinicopathologic factors were evaluated. In this study, we investigated the expression of SIP1 and LDHA in 261 cancer tissues and their matched NNM using tissue microarray. The immunohistochemistry analysis showed that the expression of SIP1 and LDHA was significantly higher in cancer tissues than in NNM (P = 0.002 P = 0.000, respectively). The expression of SIP1was significantly associated with age, Lauren grade, and histologic differentiation (P < 0.05). The expression of SIP1 was strongly correlated with LDHA expression in gastric cancer (P = 0.000, R = 0.589). The combined expression of SIP1 and LDHA was significantly associated with age, Lauren grade, and histologic differentiation (P < 0.05). Survival analysis demonstrated that the expression of SIP1 or LDHA was associated with significantly shorter overall survival (OS) (P = 0.003, P = 0.000, respectively) and disease-free survival (DFS) (P = 0.003, P = 0.000, respectively). The combined expression of SIP1 and LDHA was associated with less survival time in gastric cancer patients (P = 0.000). The multivariate analysis showed that the expressions of SIP1 and LDHA in gastric cancer (GC) were independent prognostic factors for OS (hazard ratio = 1.465, 95 %CI 1.128–1.901, P = 0.004, hazard ratio = 1.514, 95 %CI 1.091–2.101 P = 0.013, respectively) and DFS (hazard ratio = 1.461, 95 %CI 1.130–1.890, P = 0.004, hazard ratio = 1.550 95 %CL1.119–2.147 P = 0.008, respectively). Our study indicated that expressions of SIP1 and LDHA are independent prognostic factors in gastric cancer patients and may be predictive of poor outcomes.


SIP1 LDHA Gastric carcinoma Tissue microarray Prognosis 



This study was supported by grants from Research Fund for the Doctoral Program in College of Chinese Education Department (No.20102104110004) and scientific and technological projects of Liaoning Province Science and Technology Department (Nos. 2009225011-2 and 2013225049).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xuren Sun
    • 1
  • Zhe Sun
    • 2
  • Zhi Zhu
    • 2
  • Chenyan Li
    • 3
  • Junyan Zhang
    • 2
  • Huimian Xu
    • 2
  • Mingjun Sun
    • 1
    • 4
  1. 1.Department of GastroenterologyFirst Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Surgical OncologyFirst Affiliated Hospital of China Medical UniversityShenyangChina
  3. 3.Department of Endocrinology and MetabolismFirst Affiliated Hospital of China Medical UniversityShenyangChina
  4. 4.Department of Gastrointestinal EndoscopyFirst Affiliated Hospital of China Medical UniversityShenyangChina

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