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P38α高表达及术前糖类抗原19-9提示胰腺导管腺癌患者预后不良。

High Expression of P38α and Preoperative Carbohydrate Antigen 19-9 Indicate Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

作者信息

Chen Jionghuang, Zhao Ting, Jia Shengnan, Zhou Senhao, Zhou Liangjing, Wang Shaowen, Ding Guoping, Jiang Guixing, Cao Liping

机构信息

Department of General Surgery, Sir Run Run Shaw Hospital, the affiliated hospital of Zhejiang University School of Medicine, Hangzhou, China.

出版信息

J Cancer. 2018 Jan 6;9(4):650-659. doi: 10.7150/jca.21683. eCollection 2018.

Abstract

P38α is a ubiquitous protein kinase, which plays diverse roles in cancers. Surprisingly, P38α functions vary markedly in different cancers (e.g., cancer suppressor vs cancer promoter). However, there is no report on the expression of P38α, the family's most important member, in pancreatic ductal adenocarcinoma (PDAC) and its association with clinicoathological parameters and patients' prognosis. We retrospectively analyzed 152 patients who underwent surgery and were pathologically diagnosed with PDAC from September 2013 to September 2015. We used immunohistochemistry to detect P38α expression in tumor and adjacent normal tissues. The significance of the association between P38α and clinicopathological parameters was evaluated using the χ² test and t tests. The Kaplan-Meier method was used to assess the association between P38α expression and preoperative carbohydrate antigen 19-9 (CA19-9) levels and patients' overall survival. The Cox regression model was used to analyze the association between clinicopathological parameters, P38α and preoperative CA19-9 levels, and prognosis. Statistical significance was defined as < 0.05. P38α was expressed in 63.16% tumor tissues of PDAC, which was significantly higher compared with the adjacent normal tissues (26.32%, < 0.001). High expression of P38α was associated with patients' histological grade ( = 0.013), lymphatic metastasis ( = 0.025) and TNM stage ( = 0.048). The median survival time of the P38α-high group was 9.2 months, which was shorter compared with that of the P38α-low group (17.3 months, = 0.011). The median survival time of the CA19-9 > 43.63 group was 11.1 months shorter than that of the CA19-9 < 43.63 group (24.8 months, < 0.001). The Cox regression model revealed that age ( = 0.003), lymphatic invasion ( = 0.015), TNM stage ( = 0.003), histological grade ( < 0.001), preoperative CA19-9 ( = 0.049), and P38α expression ( = 0.008) were statistically significant independent risk factors affecting prognosis. Specifically, overall survival was 28.4 months in the P38α-low and CA19-9 < 43.63 groups, 16.3 months in the P38α-high or CA19-9 > 43.63 groups, and 9.7 months in the P38α-high and CA19-9 > 43.63 groups ( < 0.001). High expression of P38α was significantly associated with histological grade, lymphatic metastasis, TNM stage and prognosis in patients with PDAC. P38α and preoperative CA19-9 levels were independent risk factors affecting the prognosis of PDAC patients. High expression of p38α and preoperative carbohydrate antigen 19-9 indicate poor prognosis in patients with PDAC.

摘要

P38α是一种普遍存在的蛋白激酶,在癌症中发挥着多种作用。令人惊讶的是,P38α在不同癌症中的功能差异显著(例如,癌症抑制因子与癌症促进因子)。然而,关于该家族最重要成员P38α在胰腺导管腺癌(PDAC)中的表达及其与临床病理参数和患者预后的关系尚无报道。我们回顾性分析了2013年9月至2015年9月期间接受手术并经病理诊断为PDAC的152例患者。我们采用免疫组织化学方法检测肿瘤组织及相邻正常组织中P38α的表达。使用χ²检验和t检验评估P38α与临床病理参数之间关联的显著性。采用Kaplan-Meier法评估P38α表达与术前糖类抗原19-9(CA19-9)水平及患者总生存期之间的关联。使用Cox回归模型分析临床病理参数、P38α和术前CA19-9水平与预后之间的关联。统计学显著性定义为P<0.05。P38α在63.16%的PDAC肿瘤组织中表达,与相邻正常组织(26.32%,P<0.001)相比显著更高。P38α的高表达与患者的组织学分级(P=0.013)、淋巴转移(P=0.025)和TNM分期(P=0.048)相关。P38α高表达组的中位生存时间为9.2个月,与P38α低表达组(17.3个月,P=0.011)相比更短。CA19-9>43.63组的中位生存时间比CA19-9<43.63组短11.1个月(24.8个月,P<0.001)。Cox回归模型显示,年龄(P=0.003)、淋巴浸润(P=0.015)、TNM分期(P=0.003)、组织学分级(P<0.001)、术前CA19-9(P=0.049)和P38α表达(P=0.008)是影响预后的具有统计学显著性的独立危险因素。具体而言,P38α低表达且CA19-9<43.63组的总生存期为28.4个月,P38α高表达或CA19-9>43.63组为16.3个月,P38α高表达且CA19-9>43.63组为9.7个月(P<0.001)。P38α的高表达与PDAC患者的组织学分级、淋巴转移、TNM分期及预后显著相关。P38α和术前CA19-9水平是影响PDAC患者预后的独立危险因素。P38α的高表达和术前糖类抗原19-9表明PDAC患者预后不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b10e/5858486/bbf83e648ff8/jcav09p0650g001.jpg

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