Clinical implication of Sox9 and activated Akt expression in pancreatic ductal adenocarcinoma
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most leading causes of cancer-related death. Cancer stem cell is responsible for tumor initiation, metastasis and relapse. Sox9 is a pancreatic stem cell marker. PI3K/PTEN/Akt/mTORC is an important signal for maintaining stem cells. The purpose of this study is to determine the expression pattern of Sox9 and p-Akt in human PDAC and its correlation with prognosis. Immunohistochemical analysis was used to explore the expression of Sox9 and p-Akt in 88 human PDAC patients. The Pearson’s test was used to compare the clinicopathological parameters between negative and positive expressors. The Pearson’s correlation analysis was used to explore the relationship between Sox9 and p-Akt expression. Kaplan–Meier’s method and Cox regression analysis were used to analyze patients’ survival. The results showed that Sox9 and p-Akt overactivated in PDAC (p = 0.011, p = 0.008). Sox9-positive expression is significantly associated with distant metastasis (p = 0.046). p-Akt-positive expression is significantly associated with distant metastasis (p = 0.000), TNM stage (0.001) and PCNA expression (p = 0.000). Sox9 expression is positively correlated with p-Akt expression (r = 0.314, p = 0.003). In 54 patients with survival information, both Sox9- and p-Akt-positive expressions are associated with unfavorable prognosis (p = 0.002, p = 0.000). Sox9 and p-Akt double-positive expressor showed much poorer prognosis (p = 0.000). Cox regression analysis showed that Sox9- or p-Akt-positive expression and LN metastasis were independent prognostic factors. This study provides the first evidence that Sox9 and p-Akt are both relevant to distant metastasis and proliferation. Our data suggest the potential of Sox9 and p-Akt as prognostic biomarkers for PDAC.
KeywordsPancreatic ductal adenocarcinoma Sox9 p-Akt Prognosis
This study was supported by grants from the National Natural Science Foundation of China (Nos. 81101867, 81272542, 81200369 and 81372443), the China International Medical Foundation (CIMF-F-H001-057), the Scientific Research Project of Jiangsu Provincial Bureau of Traditional Chinese Medicine (L213236), the Medical Scientific Research Project of Jiangsu Provincial Bureau of Health (Z201206), the Special Foundation of Wu Jieping Medical Foundation for Clinical Scientific Research (Nos. 320.6753.1225 and 320.6750.12242), the Science and Education for Health Foundation of Suzhou for Youth (Nos. SWKQ1003 and SWKQ1011), the Scientific Research and Innovation Plan Project of Jiangsu Province for Postgraduate (CXLX13_838) and the Science and Technology Project Foundation of Suzhou (Nos. SYS201112, SYSD2012137 and SYS201335).
Conflict of interest
We declare that we have no conflict of interest.
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