High expression of B7‑H2 or B7‑H3 is associated with poor prognosis in hepatocellular carcinoma

Abstract

B7 family members have been associated with the signaling transduction pathways underlying tumor immune evasion in hepatocellular carcinoma. In the present study, associations between the clinical characteristics of patients with hepatocellular carcinoma (HCC) and the expression of B7-H2 and B7-H3 were analyzed. A total of 63 formalin-fixed and paraffin-embedded HCC tissues were collected to be used as a tissue microarray. Following this, the association between B7-H2/B7-H3 and the prognosis of patients with HCC was analyzed using Pearson's χ 2 test, the Kaplan-Meier method and receiver operating characteristic curve analysis. The results demonstrated that the expression of B7-H2 was significantly associated with recurrence (within 1 year) in patients with HCC (P<0.01), and that the expression of B7-H3 was associated with recurrence (within 1 year), metastasis and 2-year overall survival rate in patients with HCC (P<0.01, P=0.036 and P=0.016, respectively). In addition, the combined expression of B7-H2 and B7-H3 was associated with prognostic factors, including recurrence (within 1 year) and survival rate (within 2 years), in patients with HCC. In particular, an increased area under the curve was achieved when the combined expression of B7-H2 and B7-H3 was considered, compared with that for α-fetoprotein. Taken together, these results indicated that B7-H2- and/or B7-H3-positive expression indicates a poor clinical outcome for patients, and the combination of B7-H2 and B7-H3 may be a preferential prognostic biomarker in patients with HCC.

Identification of immunological subtypes of hepatocellular carcinoma with expression profiling of immune-modulating genes

“…The four immune subtypes were validated by IHC in 72 HCC patients from South China. The results have shown the following: (i) there is an association between high B7-H3 expression and poor survival in HCC, which is consistent with previous reports [21][22][23][24]; (ii) B7-H3 expression is positively associated with CD8 expression and a Th1/IFNγ gene signature in HCC; and (iii) patients with B7-H3 low /CD8 high subtype are correlated with favorable survival in HCCs. Our findings support the view that, despite the limited efficiency of immunotherapy, the endogenous antitumor immune response is a critical factor for survival Figure 6.…”

“…To elucidate the clinical significance of the upregulated immune checkpoints, we analyzed the relationship between these genes and overall survival (OS) of HCC patients. The results show that only two genes are significantly associated with poor OS: CD276 (B7-H3) (P = 0.014, Figure 2A) and CD47 (P = 0.039, Figure 2B), consistent with previous reports [20][21][22][23][24][25]. All the others do not have a statistically significant relationship with survival ( Supplementary Figure 1).…”

“…B7-H3 is expressed in various tumor cells and tissues, and its high expression has been associated with poor prognosis in various cancers, including HCC [21][22][23][24]. However, these studies have only focus on B7-H3 expression and its relationship with survival, and none of them has analyzed both B7-H3 and CD8 expressions simultaneously.…”

TNF‑α‑mediated epithelial‑to‑mesenchymal transition regulates expression of immune checkpoint molecules in hepatocellular carcinoma

“…B7-H3 is mostly upregulated in several cancer types, including liver, breast, bladder, colorectal, cervical, glioma, esophageal and gastric cancer (53). Previous studies have also demonstrated that dysregulation of B7-H3 in Hcc results in impaired T-lymphocyte function, thus leading to poor prognosis and recurrence (54,55). in muscle-invasive bladder cancer, high expression of B7-H3 was associated with a poor clinicopathological status and poor prognosis (56).…”

Combinational Immunotherapy for Hepatocellular Carcinoma: Radiotherapy, Immune Checkpoint Blockade and Beyond

“…inducible T cell costimulator ligand; ICOSL) and B7-H3 are being explored as novel immunotherapeutic targets in other cancer types (119). In HCC, both independent or combined expression of B7-H2 and B7-H3 have correlated to recurrence and poorer survival rate of the patients (120). Although further understanding of the tumor-promoting mechanisms by B7 ligands in the context of HCC is required, they could become promising combinatorial agents in treating HCC in the future.…”