ABSTRACT
Objective:To investigate the expression of tripartite motif 14 (TRIM14) in human pancreatic cancer and analyze its relationship with clinicopathological features and prognosis, and further explore its functional mechanism in the development and progression of pancreatic cancer.Methods:176 pairs of pancreatic cancer tissues and corresponding adjacent tissues resected by surgery in Changhai Hospital affiliated with Navy Medical University from January 2016 to December 2018 were collected. The protein expression of TRIM14 in pancreatic cancer and adjacent normal tissue was detected by immunohistochemical staining. TRIM14 and phosphorylated p65 expression in pancreatic cancer was measured by western blotting. NF-κB targeting gene Bcl-xl, CCND1, VEGF-C mRNA was tested by real time quantitative PCR. The correlation between TRIM14 expression and clinicopathological characteristics was analyzed. The relationship between TRIM14 expression and tumor-free survival and overall survival of pancreatic cancer patients was evaluated by univariate and multivariate Cox regression model. The internal relationship between TRIM14 expression and the activation of NF-κB signaling pathway was analyzed.Results:The positive TRIM14 expression rate in pancreatic cancer was obviously higher than that in adjacent normal tissue [86.93%(153/176) vs 27.27%(48/176)], and the difference was statistically significant ( P<0.05). The expression level of TRIM14 was correlated with the clinical stage, lymph node metastasis and invasion depth of pancreatic cancer ( P=0.000, 0.000, 0.021), but not obviously with gender, age, differentiation degree and distant metastasis. Cox regression analysis showed that the expression level of TRIM14 was the independent risk factor for tumor-free survival ( RR=1.706, 95% CI 1.237-2.429, P=0.029) and overall survival ( RR=1.806, 95% CI 1.984-2.831, P=0.029). The expression level of TRIM14 was tightly associated with the phosphorylation level of p65 ( R=0.86, P<0.01), and the mRNA expression of Bcl-xl, CCND1 and VEGF-C was highly correlated with TRIM14 expression ( R=0.85-0.92, P<0.01). Conclusions:TRIM14 was highly expressed in pancreatic cancer tissues and was an independent risk factor for prognosis of pancreatic cancer patients. TRIM14 participates in the development and malignant progression of pancreatic cancer potentially via activating NF-κB pathway.
ABSTRACT
Objective@#To examine the prognostic value of four important driver gene mutations in patients with radical resection of pancreatic cancer.@*Methods@#The clinical data and follow-up data of pancreatic cancer patients undergoing radical pancreatectomy and targeted sequencing from January 2016 to March 2018 at Department of Hepato-Biliary-Pancreatic Surgery, Changhai Hospital were retrospectively analyzed.There were 159 males and 88 females,aged of (60.8±8.7)years(range:33-83 years) and preoperative CA19-9 of (492.4±496.6)kU/L(range: 2-1 200 kU/L). One hundred and fifty nine cases of tumors were located in the head and 88 cases in the body and tail of the pancreas. After univariate analysis of clinical pathological factors (including gender, age, preoperative CA19-9, tumor location, tumor differentiation, pathological T and N stage, Micr. perineural invasion, Micr. lympho-vascular invasion, resection margin), the variable whose P<0.1 was included in COX regression model with four important driver gene mutations to find which mutation was related to prognosis independently. The number of gene mutations and KRAS subgroups were analyzed by Kaplan-Meier curve.@*Results@#Among 247 patients,the number of KRAS,TP53, SMAD4 and CDKN2A mutations was 212 cases(85.8%), 160 cases(64.8%), 66 cases(26.7%) and 44 cases(17.8%),respectively.KRAS mutation was correlated with the tumor differentiation and pathological T stage (χ2=24.570/6.690, P=0.000/0.035), TP53 mutation was correlated with the tumor differentiation and the resected margin(χ2=5.500/4.620, P=0.019/0.032), and CDKN2A mutation was correlated with gender(χ2=16.574, P=0.000).COX regression model analysis showed that only KRAS mutation was an independent risk factor for disease free survival and overall survival(HR=1.776, 95%CI: 1.079-2.923, P=0.024; HR=1.923, 95%CI: 1.016-3.639, P=0.045); KRASG12D mutation was associated with shorter OS(P=0.007).@*Conclusion@#KRAS and its subgroup KRASG12D mutation can be used as a prognostic index for patients with radical resection of pancreatic cancer.