title: Molecular alterations in the carcinogenesis and progression of hepatocellular carcinoma: Tumor factors and background liver factors.
abstract: Although hepatocellular carcinoma (HCC) is associated with poor prognosis worldwide, the molecular mechanisms underlying the carcinogenesis and progression of this disease remain unclear. Several tumor characteristics have previously been demonstrated to be prognostic factors of survival following hepatic resection, or the recurrence of HCC or other types of cancer. Comparisons of normal tissues and HCC tumor tissues have revealed the presence of numerous molecular alterations in HCC, including genetic and epigenetic mechanisms, particularly mutations in certain genes and DNA methylation in the promoter regions of tumor-suppressor genes. A number of studies have previously used array analysis to detect variations in the expression levels of cancer-associated genes and microRNAs, and in DNA methylation. However, an investigation of HCC tumor tissues may not determine the effect of noncancerous liver tissues (background liver) in patients with HCC. As HCC may recur multicentrically following resection, a damaged or chronically diseased HCC background liver may be considered as a pre-cancerous organ. Therefore, the influence of the background liver on HCC requires further study. Detailed studies regarding the background liver may be essential for the improved understanding of the carcinogenesis and progression of this malignancy; however only a few studies have investigated the microenvironment of the HCC background liver. The present review discusses prior molecular studies of hepatocarcinogenesis that focus on HCC and background liver tissues.
authors.affiliation: Department of Surgery, Aichi Gakuin University School of Dentistry, Nagoya 464-8651, Japan; Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Inokawa
authors.affiliation: Department of Surgery, Aichi Gakuin University School of Dentistry, Nagoya 464-8651, Japan; Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inaoka
authors.affiliation: Department of Surgery, Aichi Gakuin University School of Dentistry, Nagoya 464-8651, Japan; Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sonohara
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.affiliation: Department of Surgery, Aichi Gakuin University School of Dentistry, Nagoya 464-8651, Japan; Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
keywords: background liver factors; hepatocellular carcinoma; intrahepatic metastases; molecular alterations; multicentric occurrence