title: Clinical implication of Sox9 and activated Akt expression in pancreatic ductal adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, People's Republic of China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Xia
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Feng
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Qi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Jin
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wu
authors.forename: Haorong
authors.initials: H
authors.lastname: Wu
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Feng
authors.forename: Min
authors.initials: M
authors.lastname: Tao
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000096:biosynthesis*; D055758:SOX9 Transcription Factor / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D051057:Proto-Oncogene Proteins c-akt