Li Hao, Zhang Shi-Rong, Xu Hua-Xiang, Wang Wen-Quan, Li Shuo, Li Tian-Jiao, Ni Quan-Xing, Yu Xian-Jun, Liu Liang, Wu Chun-Tao
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 20032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
J Cancer. 2019 Jun 2;10(12):2670-2678. doi: 10.7150/jca.32072. eCollection 2019.
: SRPX2 and RAB31 play important roles in tumorigenesis and metastasis; however, their prognostic value in pancreatic cancer remains unclear. This study aimed to investigate the potential interactions and effects of SRPX2 and RAB31 on the diagnosis and prognosis of pancreatic cancer. : The expression of SRPX2 and RAB31 in pancreatic tumor tissues and cells was evaluated through database mining of the Oncomine, Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and validated the results through immunohistochemistry (IHC) and Western blot in our clinical database. Protein-protein interactions were explored by immunofluorescence and Co-immunoprecipitation (Co-IP). Two hundred tissue microarray specimens from patients (79 training and 121 validation), who underwent curative pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) were used. Additionally, the association between the SRPX2 and RAB31 and prognosis of PDAC patients after surgery was analyzed. : The expression of SRPX2 and RAB31 was highly increased in pancreatic cancer, and there was a significant positive correlation between these two proteins. Co-IP showed the direct interaction between SRPX2 and RAB31. Kaplan-Meier analysis showed that positive expression of SRPX2 and RAB31 was associated with reduced disease-free survival (DFS) and overall survival (OS) of PDAC patients in the training set and the validation sets. Furthermore, multivariate analysis indicated that the 8 edition TNM stage and combination of SRPX2 and RAB31 were independent prognostic factors that associated with OS and DFS in the training, and the validation sets, respectively. : The combination of SRPX2 and RAB31 can be important markers for the prognosis of pancreatic cancer.
SRPX2和RAB31在肿瘤发生和转移中发挥重要作用;然而,它们在胰腺癌中的预后价值仍不清楚。本研究旨在探讨SRPX2和RAB31对胰腺癌诊断和预后的潜在相互作用及影响。:通过对Oncomine、基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库进行数据挖掘,评估SRPX2和RAB31在胰腺肿瘤组织和细胞中的表达,并通过免疫组织化学(IHC)和蛋白质印迹法在我们的临床数据库中验证结果。通过免疫荧光和免疫共沉淀(Co-IP)探索蛋白质-蛋白质相互作用。使用了200例接受胰腺导管腺癌(PDAC)根治性胰腺切除术患者的组织芯片标本(79例用于训练,121例用于验证)。此外,分析了SRPX2和RAB31与PDAC患者术后预后的关系。:SRPX2和RAB31在胰腺癌中的表达显著升高,这两种蛋白之间存在显著正相关。Co-IP显示SRPX2和RAB31之间存在直接相互作用。Kaplan-Meier分析表明,在训练集和验证集中,SRPX2和RAB31的阳性表达与PDAC患者无病生存期(DFS)和总生存期(OS)缩短相关。此外,多因素分析表明,第8版TNM分期以及SRPX2和RAB31的联合分别是训练集和验证集中与OS和DFS相关的独立预后因素。:SRPX2和RAB31的联合可能是胰腺癌预后的重要标志物。