HCC is the most prevalent, among primary liver cancers and the third leading cause of cancer-related deaths worldwide [1]. In Egypt, liver cancer accounts for 1.68% of all cancer cases, with 70.48% of these cancers caused by HCC. HCC represents the main complication of cirrhosis [2]. It is characterized by having a poor prognosis and survival rate caused by the high recurrence rate, metastasis after surgical resection, and resistance to standard chemotherapy and radiotherapy [3]. Chronic hepatitis B and/or C infections in particular can hasten the onset of HCC by inciting the body’s immune system to attack the liver cells, some of which are infected with the virus while others are merely bystanders [4]. Free radicals, such as reactive oxygen species and nitric oxide reactive species, are released by activated immune system inflammatory cells, which cause DNA damage and result in carcinogenic gene mutations [5]. Despite improvements in disease diagnosis and clinical therapy, as well as knowledge of risk factors for the development of HCC, the molecular mechanisms underlying hepatocarcinogenesis are still poorly understood. Recent experimental studies have revealed that long non-coding RNAs (lncRNAs) have a significant role in the etiology of many human disorders. A very active area of study on the role of lncRNAs in the initiation, development, and metastasis of HCC has evolved during the past ten years [6]. Long non-coding RNAs (LncRNAs) are transcripts longer than 200 nucleotides but not translated into proteins [7], and the majority of them are highly expressed in differentiated tissues or certain cancer types [8]. LncRNAs influence a number of biological processes, including differentiation, development, and biogenesis, as well as a variety of human disorders, including certain malignancies [9,10]. Exosomes are considered one of the mechanisms that explain the role of LncRNAs in hepatocarcinogenesis [11]. The exosomes are membrane vesicle structures with 30 –100 nm in size, originating from the endosomes and secreted from almost all cells [12]. Evidence indicates that proteins, DNAs and various forms of RNA, including, long noncoding RNA (lncRNA), transferred by exosomes, contribute to the development of HCC, and many other diseases [13,14,15,16]. It was reported that cancer-derived exosomes mediate HCC progression through enhancing cell proliferation [17], increasing epithelial-mesenchymal transition (EMT) [18] and angiogenesis [19]. They play a critical role in immunomodulators which may cause a strong immune response [20].It was found that lncRNA, such as ROR, VLDLR, and FAL1, was enriched in HCC-derived exosomes and plays a role in the modulation of hepatoma cellular responses to sorafenib, chemoresistance, and accelerated cell proliferation and migration in HCC cases, respectively [21,22,23]. Zhang et al., reported that in patients with HCV-related HCC, the expression of lncRNA-HEIH was increased in both serum and exosomes with a higher level in exosomes than serum [24].The protein-coding gene chromobox 4 (Cbx4), which has six exons and spans about 6.26 kb, is located on chromosome 17q25. According to recent evidence, the dysregulation of this gene may alter the carcinogenic process of several tumors, including HCC, colorectal cancer, breast cancer, and others, and may be an important prognostic biomarker [28].

The aim of this study is to detect if there is an association between expression of some long non coding RNAS (LNCRNAs) as (RAMS11, LINC01564), CBX4, and TOP2A and clinical; pathological characteristic of hepatocellular carcinoma in Egyptian patients.