Proprotein Convertase Subtilisin/Kexin Type 9 Induction in Hypercholesterinemic Patients With Primary and Metastatic Liver Tumors

Abstract

Background/aim: Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels are positively associated with serum cholesterol levels, which contribute to the growth of cancers. PCSK9 levels are low in patients with liver cirrhosis, with a high incidence of hepatocellular carcinoma (HCC). PCSK9 expression is increased in colorectal cancer (CRC), but serum levels in these patients have not been analyzed. Therefore, serum PCSK9 may serve as a diagnostic marker to differentiate between liver metastases from CRC and HCC.

Patients and methods: Serum PCSK9 was measured by ELISA in 36 patients with CRC metastases, 32 patients with HCC and 59 healthy controls.

Results: The serum PCSK9 levels of these three cohorts were similar. Serum PCSK9 levels were not associated with the tumor node metastasis (TNM) stage. Liver steatosis, inflammation and fibrosis scores did not correlate with serum PCSK9 levels. Cancer patients with hypercholesterolemia had elevated PCSK9 levels. These patients had higher TNM stages and Union for International Cancer Control scores in both cohorts. PCSK9 levels were also elevated in patients with viral hepatitis. When patients with hepatitis and hypercholesterolemia were excluded, serum PCSK9 levels were low in cancer patients compared to controls. Serum PCSK9 levels did not correlate with the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in HCC and CRC patients. In the latter cohort, PCSK9 and alpha-fetoprotein were positively correlated.

Conclusion: Serum PCSK9 is increased in patients with CRC metastases or HCC with hypercholesterolemia. This suggests that patients with high cholesterol levels may benefit most from PCSK9 blockage.

Keywords: Hepatocellular carcinoma; colorectal cancer; hypercholesterolemia.