Prognostic Value and Potential Immunoregulatory Role of SCARF1 in Hepatocellular Carcinoma

Abstract

Scavenger receptor class F member 1 (SCARF1) is thought to play an important role in the selective recruitment of CD4 + T cells to liver sinusoidal endothelial cells during chronic liver disease. However, the contribution of SCARF1 to hepatocellular carcinoma (HCC) is currently unknown. We utilized publically-available RNA-sequencing data from The Cancer Genome Atlas (TGCA) to explore SCARF1 expression in HCC and correlated it with a number of clinicopathological features. Flow adhesion assays were used to determine the role of SCARF1 in CD4 + T cell subset recruitment. SCARF1 expression was downregulated in HCC tumor tissues, compared to non-tumoral tissues, and loss of SCARF1 expression was associated with poorly differentiated/aggressive tumors. Additionally, higher SCARF1 expression in HCC tumor tissues was highly prognostic of better overall, disease-free and progression-free survival. SCARF1 within HCC was largely associated with tumor endothelial cells and adhesion studies suggested that it played a role in the specific recruitment of proinflammatory CD4 + T cells (CD4 + CD25 −) to HCC tumor tissues. Endothelial SCARF1 expression in tumor biopsies may provide critical prognostic information. Additionally, SCARF1 may also be a novel endothelial target that could help re-programme the microenvironment of HCC by promoting effector T cell tumor infiltration.

Exploring the prognostic value of SCARF1 in non-small cell lung cancers

“…Scavenger receptors have previously been show to bind a range of oncogenic ligands, such as heat shock proteins (HSPs) [35,36] and bacterial lipopolysaccharide (LPS) [37][38][39] and are known to be involved in the pathophysiology of a range of cancers [40]. Indeed, we have previously explored two such receptors, SCARF1 [11] and stabilin-1 [41], in the context of hepatocellular carcinoma (HCC) and…”

“…Recent work from our lab has focussed on the expression and function of a largely understudied scavenger receptor [23], SCARF1 (scavenger receptor class F, member 1), in human liver tissues [11,22]; however, others have also identified its presence in human lung tissues [18]. Here, we show that the lungs are a site of significant SCARF1 expression ( Figure 1A) and, like the liver [22], endothelial cells account for the majority of its expression ( Figure 1B).…”

“…We have previously shown that SCARF1 is highly present in in human liver tissues [11,22]; however, the exploration of its expression in other major organs is limited.…”

“…fibroblast) populations [9,10] of NSCLC tumours, whilst other tumour-resident cells, such as endothelial cells, are less well studied. We have previously described the prognostic value of the endothelial-expressed scavenger receptor class F, member 1 (SCARF1) in hepatocellular carcinoma (HCC) and hypothesised that it plays a key role in the recruitment of proinflammatory CD4 + T cells to the HCC tumour microenvironment [11]; here, we sought to study SCARF1 in the context of NSCLCs.…”

“…Loss of SCARF1 expression is associated with more advanced and aggressive tumours in LUAD, but not LUSCPreviously, we have shown that a loss of SCARF1 expression in hepatocellular carcinoma tumours is associated with more aggressive tumour biology[11]; here, we aimed to utilise the TGCA dataset to explore whether this was also the case in NSCLCs. Firstly, we explored SCARF1 expression levels in cases of NSCLCs at different stages of the disease, from early stage disease(Stage I)through to highly developed and metastatic disease (Stage IV).…”