Abstract
In many gastric cancer patients, the disease is diagnosed in an advanced stage and therefore the mortality levels are high. Because there is a need to identify novel early diagnostic and prognostic biomarkers, we tested whether SIRT1 and STAT3 are good candidates. Towards this, we used patient tissues representing different stages of gastric cancer including gastric pre-cancerous lesions, early gastric cancer, and advanced gastric cancer, and probed SIRT1, STAT3 and phosphorylated STAT3 (pSTAT3) levels using immunohistochemistry. Our results revealed upregulated expression of SIRT1 in all stages of gastric cancer compared with noncancerous gastric mucosa, suggesting that high SIRT1 levels are likely involved in establishing gastric neoplasticity. However, STAT3 and pSTAT3 levels remained low until the gastric mucosa reached the tumor stage. Moreover, co-ordinated high expression of SIRT1 and STAT3 predicted poor overall survival for advanced gastric cancer patients. In addition, through analysis of gastric cancer patients from the TCGA dataset, we identified SIRT2 as an independent prognostic factor in gastric cancer patients. We postulate that SIRT1 and STAT3 are potential early diagnostic and prognostic markers of gastric cancer. Our study also shows that SIRT1 acts a gatekeeper during gastric tumorigenesis.
Highlights
Gastric cancer is the third leading cause for cancer deaths worldwide
Our results revealed upregulated expression of SIRT1 in all stages of gastric cancer compared with noncancerous gastric mucosa, suggesting that high SIRT1 levels are likely involved in establishing gastric neoplasticity
Based on the criteria set by the Union for International Cancer Control (UICC) TNM Classification of Malignant Tumors 7th edition, advanced gastric cancer (AGC) patients were in stage I, of them in stage II, 30 of them in stage III and 12 of them in stage IV (Table 2)
Summary
Gastric cancer is the third leading cause for cancer deaths worldwide. In China, it is the third most commonly diagnosed cancer and the second leading cause of cancerrelated death [1, 2]. Since many patients are diagnosed with gastric cancer in an advanced stage, the prognosis is poor with an average 5-year survival rate of 14–25%, in spite of the use of conventional therapies such as surgery, chemotherapy, and radiotherapy [3]. Gastric cancer predominantly initiates from atrophic gastritis and undergoes a sequence of intestinal metaplasia, dysplasia followed by carcinoma [4]. Novel and diverse early diagnostic or prognostic markers and therapeutic targets for gastric cancer are required for efficient clinical detection of the cancer at an early stage
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