DNASE1L3 as an indicator of favorable survival in hepatocellular carcinoma patients following resection.

Shuncong Wang,Xiangqiong Mo,Haiqing Ma,Haiyu Zhang,Xingwei Liu,Lewei Yang,Xuemin Li,Yan Yan,Guangwei Yang,Huanhuan Sun,Yun Deng

doi:10.18632/aging.102675

Shuncong Wang, Xiangqiong Mo + Show 9 more

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https://doi.org/10.18632/aging.102675

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Hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis. It is of great importance to identify biomarkers for the prediction of patients’ survival.The mRNA expression level of deoxyribonuclease 1 like 3 (DNASE1L3) and its correlation with survival were accessed in 424 samples from The Cancer Genome Atlas database. Its expression level was confirmed by real-time quantitative polymerase chain reaction and western blotting in 20 pairs of postsurgical specimens. In addition, immunohistochemistry staining of DNASE1L3 was also performed in 113 postoperative samples, using a histochemistry score system. The relationship between patients’ survival and DNASE1L3 expression level was evaluated by the Kaplan-Meier method.DNASE1L3 is downregulated in both mRNA and protein levels in HCC tissues, compared with adjacent normal tissues. 52 of 113 HCC specimens showed positive DNASE1L3 protein expression. Patients with positive DNASE1L3 expression had significantly longer overall survival, compared with patients with negative expression (p = 0.023). However, the DNASE1L3 fails to discriminate progression-free survival (p = 0.134). Multivariate COX analysis revealed that positive DNASE1L3 expression and higher differentiation were significantly associated with better overall survival.This study demonstrated that positive DNASE1L3 expression is an independent prognostic factor for better survival in HCC patients following radical resection.

Highlights

Hepatocellular carcinoma (HCC) represents a malignancy originating from hepatocytes mostly arising from cirrhosis, accounting for more than 90% of primary liver cancer
To further confirm the aforementioned differential mRNA expression of DNASE1L3 and its implication on prognosis in patients after radical resection for HCC (Table 1), we performed real-time quantitative polymerase chain reaction (RT-qPCR), western blotting and IHC staining on postsurgical specimens
We demonstrated that the positive DNASE1L3 expression is associated with better progression-free survival (PFS) and overall survival (OS) in the HCC patients after radical resection

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Introduction

Hepatocellular carcinoma (HCC) represents a malignancy originating from hepatocytes mostly arising from cirrhosis, accounting for more than 90% of primary liver cancer. The global age-standardized incidence rate for HCC is 10.1 patients per 100,000 person-years, with 80% of cases occurring in East Asia and Africa [1]. The World Health Organization estimated that the number of patients died from liver cancer may exceed 1 million in 2030 [3]. The risk factors for HCC include hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, excessive alcohol intake, aflatoxin and positive family history [4]. All these factors cause deoxyribonucleic acid (DNA) damage and gene mutations of whom accumulation promotes chronic inflammation, fibrosis and eventually development of HCC [5,6,7,8]. Universal adoption of HBV vaccination, implantation of direct-acting anti-HCV agents and increased incidence of metabolic syndrome and obesity are changing the etiological spectrum of HCC, especially in western countries

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