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SIRT1和STAT3的协同过表达与胃癌患者的不良生存结局相关。

Co-ordinated overexpression of SIRT1 and STAT3 is associated with poor survival outcome in gastric cancer patients.

作者信息

Zhang Shu, Huang Shuling, Deng Chao, Cao Yu, Yang Jun, Chen Guangxia, Zhang Bin, Duan Chaoqin, Shi Jiong, Kong Bo, Friess Helmut, Zhao Nanyi, Huang Chen, Huang Xiaoli, Wang Lei, Zou Xiaoping

机构信息

Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.

Jiangsu Clinical Medical Center of Digestive Disease, Nanjing, China.

出版信息

Oncotarget. 2017 Mar 21;8(12):18848-18860. doi: 10.18632/oncotarget.14473.

DOI:10.18632/oncotarget.14473
PMID:28061480
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5386652/
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.

摘要

在许多胃癌患者中，疾病在晚期才被诊断出来，因此死亡率很高。由于需要识别新的早期诊断和预后生物标志物，我们测试了SIRT1和STAT3是否是合适的候选物。为此，我们使用了代表胃癌不同阶段的患者组织，包括胃癌前病变、早期胃癌和晚期胃癌，并通过免疫组织化学检测SIRT1、STAT3和磷酸化STAT3（pSTAT3）的水平。我们的结果显示，与非癌性胃黏膜相比，SIRT1在胃癌的所有阶段表达上调，这表明高SIRT1水平可能与胃肿瘤形成有关。然而，直到胃黏膜发展到肿瘤阶段，STAT3和pSTAT3水平一直保持较低。此外，SIRT1和STAT3的协同高表达预示着晚期胃癌患者的总体生存率较差。此外，通过对TCGA数据集中的胃癌患者进行分析，我们确定SIRT2是胃癌患者的一个独立预后因素。我们推测SIRT1和STAT3是胃癌潜在的早期诊断和预后标志物。我们的研究还表明，SIRT1在胃肿瘤发生过程中起守门人的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/c03d48409a65/oncotarget-08-18848-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/5f46ff290799/oncotarget-08-18848-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/32b489731e1f/oncotarget-08-18848-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/98fe3a9c6d29/oncotarget-08-18848-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/c03d48409a65/oncotarget-08-18848-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/5f46ff290799/oncotarget-08-18848-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/32b489731e1f/oncotarget-08-18848-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/98fe3a9c6d29/oncotarget-08-18848-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a1d/5386652/c03d48409a65/oncotarget-08-18848-g004.jpg

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