Potentiality of α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) in prognosis prediction and immunotherapy response for patients with hepatocellular carcinoma

Abstract

ABSTRCT The α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) have certain diagnostic value, but their potential value in prognosis prediction, especially immunotherapy response prediction, remains unclear in liver cancer. Through the tumor-free survival (TFS) and overall survival (OS) rates analyses of serum AFP and sICAM-1 levels in 87 patients with primary hepatocellular carcinoma (HCC), the patients whose AFP and sICAM-1 levels were normal (AFP < 20 μg/L or sICAM-1 < 1000 μg/L) before surgery or recovered to normal after surgery exhibited a lower tumor recurrence rate and better OS than patients with elevated serum levels of the two markers. Combined analysis showed that patients with synchronously elevated levels of AFP and sICAM-1 showed the lowest TFS and OS. In addition, the RNA-seq data and clinical information of The Cancer Genome Atlas Liver Hepatocellular Carcinoma were collected to analyze the predictive values of AFP and ICAM-1 in the diagnosis, prognosis and immunotherapy of HCC. The results indicated that the combined application of the two indicators had higher accuracy in both the diagnosis and prognostic prediction of HCC by receiver operating characteristic curves. AFP and ICAM-1 were significantly correlated with multiple immune cells in HCC samples but not in normal samples. The patients with low expression of the two indicators were most likely to benefit from the immune checkpoint blockade therapy. In conclusion, AFP and ICAM-1 play vital roles in the diagnosis, prognostic prediction, and immunotherapy of HCC, suggesting that they are considered as prognostic predictors in clinical practice.

Combination of alpha-fetoprotein and neutrophil-to-lymphocyte ratio to predict treatment response and survival outcomes of patients with unresectable hepatocellular carcinoma treated with immune checkpoint inhibitors

“…Emerging evidence suggests that AFP is closely associated with the prognosis of patients with HCC treated with immunotherapy. A clinical trial reported that AFP had important value in immunotherapy response prediction for HCC patients [ 25 ]. Sun et al [ 26 ].…”

Current state and challenges of emerging biomarkers for immunotherapy in hepatocellular carcinoma (Review)

“…The AFP levels are increased in ~two-thirds of patients with HCC (21). The expression levels of certain immune checkpoint proteins, such as SIGLEC15, CTLA4, CD274, PDCD1LG2, PDCD1, TIGIT, LAG3 and HAVCR2, have been revealed to differ with regards to the AFP level (22). It has been suggested that AFP could be used as a prognostic biomarker for HCC immunotherapy.…”

Non-Invasive Biomarkers for Immunotherapy in Patients with Hepatocellular Carcinoma: Current Knowledge and Future Perspectives

“…Lower serum levels of AFP and soluble intercellular adhesion molecule 1 (sICAM-1)—a soluble factor derived from endothelial cells and involved in inflammatory responses, which is absent in normal hepatocytes [ 75 , 76 ]—were associated with a response to immunotherapy in a recent analysis of the Cancer Genome Atlas Liver Hepatocellular Carcinoma. AFP and ICAM-1 upregulation correlate with an immunosuppressive TME in which CD4 T cells, macrophages, and monocytes are predominant, and the expression of immune checkpoints such as T cell immunoglobulin and ITIM domain (TIGIT), Hepatitis A virus cellular receptor 2 (HAVCR2), PD-1, CTLA4, and LAG3 is enhanced [ 77 ].…”