Zhonghua wai ke za zhi [Chinese journal of surgery] | 14 Mar 2019
L Zhou, WW Sheng, XY Shi, JP Zhou and M Dong
Objective: To study the expression of ISYNA1 and association of ISYNA1 with clinicopathological significance in pancreatic ductal adenocarcinoma (PDAC). Methods: Collecting clinical data and specimens of 68 PDAC patients at Department of General Surgery, the First Hospital of China Medical University from March 2008 to December 2017.There were 39 males and 29 females, aged 33 to 81 years(median 59 years).The expression of ISYNA1 in 68 paraffin embedded PDAC specimens was detected by immunohistochemistry,in which 34 had paired non-cancerous pancreatic tissues,the relationship between ISYNA1 expression and clinicopathological parameters was analyzed; and the correlation between ISYNA1 and p53 in 48 PDAC specimens were estimated.qRT-PCR and Western blot were used to examine the expression of ISYNA1 mRNA and protein level in 17 paired fresh PDAC specimens and adjacent non-cancerous pancreatic tissues,respectively.siRNA interference was used to knockdown the expression of p53 in Capan-2,SW1990 and Miapaca-2 cells,and association of p53 with ISYNA1 expression was explored. Statistical methods included Student’s test,χ(2) test, Kaplan-Meier curve, Log-rank test and Pearson analysis, respectively. Results: Immunohistochemistry results showed that the expression of ISYNA1 in PDAC(3.681±2.198)was significantly lower than that in normal pancreatic tissues(6.012±3.428)(t=-3.611,P=0.001).In 17 paired fresh PDAC specimens,ISYNA1 mRNA expression in non-cancerous pancreatic tissues(()ΔC(T): (3.721±2.234)was obviously higher than that in PDAC tissues ()ΔC(T): (5).889±1.607) (t=-4.636,P<0.01), and ISYNA1 protein level in non-cancerous pancreatic tissues(0.815±0.418)was similarly higher than that in PDAC tissues(0.517±0.240)(t=2.948,P=0.009).χ(2) test showed the expression of ISYNA1 was negatively associated with tumor invasion depth(χ(2)=7.534,P=0.030)and vascular invasion(χ(2)=5.048,P=0.043);Pearson analysis showed there was no relationship between ISYNA1 and mutant p53(χ(2)=1.377,P=0.359).In p53 wild-type Capan-2 and SW1990 cells,Knockdown of p53 significantly down regulated ISYNA1 expression, whereas had no effect on ISYNA1 expression in p53 mutant Miapaca-2 cells. Kaplan-Meier survival analysis and Log-Rank test indicated patients with negative ISYNA1 expression had a shorter median survival time and poorer prognosis(χ(2)=4.953, P=0.026). Conclusions: The expression of ISYNA1 in PDAC tissues is significantly decreased,which is associated with the prognosis of PDAC patients,it is only related to wild type p53,and has no relationship with mutant p53.Abnormal expression of ISYNA1 may play an important role in the progression of PDAC.
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