title: Possible involvement of PCSK9 overproduction in hyperlipoproteinemia associated with hepatocellular carcinoma: A case report.
abstract: Herein, we describe a 69-year-old Japanese man with massive type III hyperlipoproteinemia (total cholesterol, 855 mg/dL; triglyceride, 753 mg/dL) presenting as a paraneoplastic manifestation of hepatitis B virus-associated hepatocellular carcinoma. The messenger RNA expression of sterol regulatory element-binding protein-2 and proprotein convertase subtilisin/kexin 9 in the tumor tissue was increased by 13-fold and 4-fold, respectively, compared with the non-tumor tissue. Serum level of active form of PCSK9 was 382 ng/mL (reference range: 253 ± 79 ng/mL). The non-tumor tissue had extremely low expression of low-density lipoprotein receptor and low-density lipoprotein receptor-related protein 1. Together, we speculate that marked overexpression of sterol regulatory element-binding protein-2 in the tumor may stimulate the secretion of PCSK9, which inhibits the lipoprotein receptors in the non-tumor tissue, thereby causing paraneoplastic hyperlipoproteinemia.
authors: Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi, Japan. Electronic address: syu1.n@jichi.ac.jp.
authors: Shuichi
authors: S
authors: Nagashima
authors: Department of Surgery, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi, Japan.
authors: Kazue
authors: K
authors: Morishima
authors: Division of Virology, Department of Infection and Immunity, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi, Japan.
authors: Hiroaki
authors: H
authors: Okamoto
authors: Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi, Japan. Electronic address: ishibash@jichi.ac.jp.
authors: Shun
authors: S
authors: Ishibashi
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications*; D006801:Humans; D006951:Hyperlipoproteinemias / Q000150:complications* / Q000378:metabolism*; D008113:Liver Neoplasms / Q000150:complications*; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9 / Q000096:biosynthesis*; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Cholesterol; Hepatitis B virus; Hepatocellular carcinoma; Hypercholesterolemia; Hypertriglyceridemia; LDL receptor; Liver; PCSK9; SREBP-2; Type III hyperlipoproteinemia