# Extracellular glypican‐1 affects tumor progression and prognosis in esophageal cancer

## TL;DR

This study shows that high levels of glypican-1 in blood are linked to worse outcomes in esophageal cancer and may help predict disease progression.

## Contribution

The study identifies extracellular glypican-1 as a novel biomarker for esophageal cancer prognosis and progression.

## Key findings

- High preoperative plasma GPC1 levels correlate with advanced tumor stage and poor survival in ESCC patients.
- Extracellular GPC1 enhances cancer cell migration and invasion, contributing to tumor progression.
- Plasma GPC1 is a non-invasive biomarker for ESCC prognosis and a potential therapeutic target.

## Abstract

Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported that the formation of the GCX is promoted on cancer cells and is associated with tumor growth and metastasis. Heparan sulfate proteoglycan glypican‐1 (GPC1) is a core protein of the GCX that is overexpressed in esophageal squamous cell carcinoma (ESCC) and is involved in the development and progression of cancer cells. The purpose of the present study is to analyze the utility of GPC1 as a new biomarker ralated to glycocalyx that reflects therapeutic effect and prognosis of ESCC.

We measured the concentration of GPC1 protein in preoperative plasma from advanced esophageal cancer patients and examined its relationships with clinicopathological factors and therapeutic efficacy, and the effects of extracellular GPC1 were investigated.

The following clinical factors were significantly correlated with the preoperative high GPC1 concentration: male, tumor size ≥30 mm, venous invasion, pT factor ≥2, pStage ≥3, residual tumor, and distant metastatic recurrence. Both overall and recurrence‐free survival were significantly worse in the high GPC1 group. Extracellular GPC1 protein concentration reflected intracellular GPC1 expression. Furthermore, we examined the effects of extracellular recombinant human (rh)GPC1 on ESCC cells, and found that extracellular rhGPC1 affects cell motility, including migration and invasion.

These results demonstrated the utility of extracellular GPC1 as a biomarker, which can be assayed from a less invasive blood sample‐based liquid biopsy. Extracellular GPC1 protein plays a role in both tumor cell motility and cancer progression. Thus, plasma GPC1 is a useful biomarker for esophageal cancer progression and may be a potential candidate of therapeutic target.

This study presents novel findings on the role of glypican‐1 (GPC1) in esophageal squamous cell carcinoma (ESCC). We confirmed that high concentrations of GPC1 protein in preoperative plasma are significantly related to advanced stage and distant metastatic recurrence and was an independent poor prognostic factor in ESCC patients (p = 0.010, HR = 4.22). Furthermore, this research elucidates the role of extracellular GPC1 in enhancing cancer cell motility, thus contributing to tumor progression.