The role of different PI3K protein subtypes in the metastasis, angiogenesis and clinical prognosis of hepatocellular carcinoma

Ann Diagn Pathol. 2021 Aug:53:151755. doi: 10.1016/j.anndiagpath.2021.151755. Epub 2021 May 11.

Abstract

Background and objectives: Abnormal activation of the PI3K/AKT pathway is closely related to tumor occurrence, development and angiogenesis. PI3K, as a key protein in the PI3K/Akt pathway, has different subtypes that play diverse roles in various tumors. The aim of this study was to examine the roles of different PI3K protein subtypes (PI3Kp110α, PI3Kp110β, and PI3Kp110δ) in the metastasis, angiogenesis and prognosis of hepatocellular carcinoma (HCC).

Methods: The roles of different PI3K protein subtypes in the metastasis, angiogenesis and prognosis of HCC were assessed by immunohistochemical staining of 97 HCC tissues and the STRING database.

Results: Our results showed that PI3Kp110α and PI3Kp110δ were associated with HCC metastasis and angiogenesis. Patients with high expression of PI3Kp110α and PI3Kp110δ had a worse prognosis and shorter survival time, respectively, than those with low expression, whereas these effects were not observed for PI3Kp110β. Cox regression analysis showed that PI3Kp110α and clinical stage were independent risk factors for the overall survival of HCC patients.

Conclusions: PI3Kp110α and PI3Kp110δ promoted HCC metastasis and angiogenesis via the PI3K/AKT pathway, and PI3Kp110α was an independent risk factor for HCC patients. These findings provide valuable insights for the prognosis evaluation and the selection of subtype inhibitors of HCC patients.

Keywords: Angiogenesis; Metastasis; PI3Kp110α; PI3Kp110β; PI3Kp110δ.

MeSH terms

  • Adult
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Case-Control Studies
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry / methods
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Neoplasm Staging / methods
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Phosphatidylinositol 3-Kinases / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Risk Factors
  • Survival Analysis
  • Up-Regulation