Prognostic significance of XRCC4 expression in hepatocellular carcinoma

Abstract

BackgroundOur previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment.Materials and MethodsWe conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE. The levels of XRCC4 expression were tested using immunohistochemistry. The sensitivity of cancer cells to anti-cancer drug doxorubicin was evaluated using the half-maximal inhibitory concentration (IC50).ResultsXRCC4 expression was significantly correlated with pathological features including tumor stage, liver cirrhosis, and micro-vessel density. XRCC4 expression was an independent prognostic factor of hepatocarcinoma, and TACE treatments had no effects on prognosis of hepatocarcinoma patients with high XRCC4 expression. More intriguingly, TACE improved the prognosis of hepatocarcinoma patients with low XRCC4 expression. Functionally, XRCC4 overexpression increased while XRCC4 knockdown reduced the IC50 of cancer cells to doxorubicin.ConclusionsThese results suggest that XRCC4 may be an independent prognostic factor for hepatocarcinoma patients, and that decreasing XRCC4 expression may be beneficial for post-operative adjuvant TACE treatment in hepatocarcinoma.

Micro RNA‐4651 Serves as a Potential Biomarker for Prognosis When Selecting Hepatocellular Carcinoma Patients for Postoperative Adjuvant Transarterial Chemoembolization Therapy

“…However, many studies have suggested that pa‐TACE displays different therapeutic effects on hepatocellular carcinoma with different genetic profiles. For example, different genetic features such as different expression of polycomb chromobox 4 and x‐ray repair complementing 4 among individuals with hepatocellular carcinoma have been proven to modify MVD, and ultimately lead to unsuccessful pa‐TACE treatment . Genetic changes in a disintegrin and metalloproteinase with thrombospondin motifs 5, microRNA‐1268a, microRNA‐196a, and microRNA‐499a may change individual's response to pa‐TACE treatment and result in treatment failure …”

“…For example, different genetic features such as different expression of polycomb chromobox 4 and x-ray repair complementing 4 among individuals with hepatocellular carcinoma have been proven to modify MVD, and ultimately lead to unsuccessful pa-TACE treatment. (30,32) Genetic changes in a disintegrin and metalloproteinase with thrombospondin motifs 5, microRNA-1268a, microRNA-196a, and microRNA-499a may change individual's response to pa-TACE treatment and result in treatment failure. (15,31) In this study, we are particularly concerned with the association between microRNA-4651 expression in cancerous tissues and pa-TACE treatment, primarily because our previous reports showed a higher serum mciroRNA-4651 level among patients with aflatoxin B1-related hepatocellular carcinoma, and this upregulation significantly correlated with tumor angiogenesis and prognosis.…”

“…Microvessel density (MVD) in tumor tissues was evaluated according to our previously published immunohistochemistry . In this study, the MVD was divided into two groups: low density (number of microvessels ≤ 50/×200 magnifications) and high density (number of microvessels > 50/×200 magnifications).…”

“…Microvessel density (MVD) in tumor tissues was evaluated according to our previously published immunohistochemistry. (23,27,30) In this study, the MVD was divided into two groups: low density (number of microvessels ≤ 50/×200 magnifications) and high density (number of microvessels > 50/×200 magnifications). (3) Cases with multiple tumors more than 5 cm or tumor involving a first or second branch of the portal or hepatic veins (4) The tumor with multiple lesions localized in one lobe of liver, or the main tumor localized in one lobe only with a small solitary lesion in contralateral lobe, or tumor involving a first or second branch of the portal or hepatic vein, which could be safely resected without grossly remaining tumors, and the patient was judged to have well preserved liver function to survive the operation (5) Cases underwent partial hepatectomy, and agreed to pa-TACE treatment…”

X-Ray Repair Cross Complementing 4 (XRCC4) Genetic Single Nucleotide Polymorphisms and the Liver Toxicity of AFB1 in Hepatocellular Carcinoma

“…In the past decades, growing reports have exhibited that the abnormal structures and functions of XRCC4 may alter the capacity of DNA repair and ultimately result in human diseases [17][18][19][20][21][22]. Several recent studies have also shown that the genetic alterations in the coding regions of XRCC4 can modify hepatocellular carcinoma (HCC) risk and prognosis [23][24][25][26][27]. However, the effects of this genetic alteration on the hepatic toxicity of AFB1 is unclear.…”