KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion.

Jing Chen,Cui-Cui Zhao,Fei-Ran Chen,Fei Luo,Tao Jiang,Guo-Wei Feng,Wen Shi

doi:10.1155/2021/8249293

Abstract

Background Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed (P < 0.05) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) (P < 0.05, respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control (P < 0.05, respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

Highlights

Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis
We explored the relationship between kinesin superfamily 4A (KIF4A) and the clinical outcome of pancreatic ductal adenocarcinoma (PDAC) through a fiveyear follow-up and found that KIF4A is closely related to TNM staging, tumor grade, lymph node metastasis, and vascular tumor suppository
We examined the protein expression of KIF4A in peripheral blood and in the tumor and found that KIF4A is of guiding significance for the prognosis of pancreatic cancer, and the expression of KIF4A can be found in many other kinds of tumors (Supplementary Figure S1)

Summary

Introduction

Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. The high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. Kinesin superfamily 4A (KIF4A) had recently been found to play a role in a variety of tumors including lung and hepatocellular carcinoma and was proved to be closely related to tumor metastasis, recurrence, and many other clinical features associated with poor prognosis [3,4,5]. KIF4A had previously been shown to be highly expressed in PDAC [6]; the mechanism of KIF4A in tumor development remained unclear and worth discussing

Objectives

Results

Conclusion