Clinical significance of LAG-3 on microvessel density in primary hepatocellular carcinoma

Indian J Pathol Microbiol. 2022 Jul-Sep;65(3):581-588. doi: 10.4103/ijpm.ijpm_620_21.

Abstract

Aims: We aimed to determine whether lymphocyte activation gene 3 (LAG-3), also known as CD223, is associated with microvessel density (MVD) in primary hepatocellular carcinoma (HCC), as well as their clinical significance in predicting survival.

Materials and methods: One hundred and twenty-seven patients were enrolled in the study. Samples were obtained on resection at the Department of Hepatobiliary Surgery of the Qingdao Municipal Hospital from June 2014 to June 2016. Immunohistochemistry was used to determine vessel density and LAG-3 abundance. Statistical analyses were performed to test for correlation of LAG-3 density and other clinicopathological variables with overall survival (OS).

Results: High LAG-3 abundance was significantly correlated with increased MVD in primary HCC (P < 0.05). The χ2 test revealed a significant association of LAG-3 with preoperative AFP level, tumor diameter, N stage, and the presence of HBV infection (P < 0.05). Patients with high LAG-3 expression had shorter OS compared to those with low LAG-3 expression (P < 0.05). The Cox proportional hazards model showed that both higher LAG-3 and MVD density, age, the number of tumors, preoperative AFP level, tissue differentiation, Child-Pugh grade, and lymph node metastasis correlated with survival.

Conclusions: High expression of LAG-3 is associated with angiogenesis and poor prognosis in HCC patients. With the deepening of research, LAG-3 is likely to become a novel biomarker for clinical diagnosis and prognosis and can even be a therapeutic target of HCC.

Keywords: Clinicopathological Features; LAG-3; MVD; primary hepatocellular carcinoma; prognosis.

MeSH terms

  • Antigens, CD / metabolism*
  • Carcinoma, Hepatocellular* / pathology
  • Humans
  • Liver Neoplasms* / pathology
  • Lymphocyte Activation Gene 3 Protein
  • Microvascular Density
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • alpha-Fetoproteins

Substances

  • Antigens, CD
  • alpha-Fetoproteins
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human