Quantitative proteomics reveals FLNC as a potential progression marker for the development of hepatocellular carcinoma.

Yingzi Qi,Yao Zhang,Tao Zhang,Xing Wang,Fengxu Fan,Lingsheng Chen,Wei Wei,Ping Xu,Lingqiang Zhang,Feng Xu,Na Su,Xue Qin,Yanchang Li,Yinkun Liu,Zhongwei Xu

doi:10.18632/oncotarget.11921

Abstract

Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection is one of the most life-threatening human cancers in China. However, the pathogenesis of HCC development is still unclear. Here, we systemically analyzed liver tissues from different stages of HCC patients through 8-plex Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) approach. A total of 4,620 proteins were identified and 3,781 proteins were quantified. When T1, T2 and T3 tumor tissues were compared with T1 non-tumor cells, 330, 365 and 387 differentially expressed proteins were identified respectively. IPA (Ingenuity Pathway Analysis) analysis revealed that these differentially expressed proteins were involved in endothelial cancer, cell spreading, cell adhesion and cell movement of tumor cell lines pathway and so on. Further study showed that the filamin C (FLNC) protein was significantly overexpressed with the development of HCC, which might play an important role in HCC invasion and metastasis. These results were also confirmed with western blot (WB). The mRNA levels were significantly increased in 50 pairs of tumor and adjacent non-tumor tissues from TCGA database. The higher expression of FLNC in HCC might be a common phenomenon, thereby shedding new light on molecular mechanism and biomarker for the diagnosis purpose of HCC development.

Highlights

Hepatocellular carcinoma (HCC) is the fifth-most frequently diagnosed cancer in men, the secondleading cause of cancer mortality worldwide [1]
Further study showed that the filamin C (FLNC) protein was significantly overexpressed with the development of HCC, which might play an important role in HCC invasion and metastasis
Sixteen paired samples including both tumor and adjacent non-tumor tissues were classified into three phases including T1N0M0, T2N0M0 and T3N0M0 according to the tumor-node-metastasis (TNM) classification of malignant tumors provided by the International Union Against Cancer (UICC)

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth-most frequently diagnosed cancer in men, the secondleading cause of cancer mortality worldwide [1]. Potentially curative treatments for HCC include hepatectomy, transplantation, or local ablative therapy [3]. While these treatments are promising, the clinical practice has shown that the patients treated for early HCC lesions can have high survival rates and low chances of recurrence and metastasis. Alphafetoprotein (AFP) is one of the biomarkers used widely for early diagnosis of HCC. The recurrence after resection and personalized treatment of HCC are still very challenging in clinical practice. Deep understanding of the mechanism behind the onset and development of HCC induced by HBV will help to solve these problems [6]

Methods

Results

Conclusion