Soluble podoplanin as a biomarker in diffuse‑type gastric cancer

Abstract

Diffuse-type gastric cancer, also known as scirrhous gastric cancer, is characterized by a larger number of stromal cells, referred to as cancer-associated fibroblasts (CAFs), than the number of cancer cells in the tissue. The present study focused on CAFs in gastric cancer and examined their potential as a blood biomarker. A total of 46 and 84 patients with gastric cancer were respectively included in a development and an independent validation cohort to assess the clinicopathological characteristics of plasma podoplanin (PDPN) levels. The prognostic impact of plasma PDPN was also investigated in the validation cohort. The cut-off value of the plasma-PDPN concentration was set to the median plasma PDPN concentration in the development cohort that was then divided into the high-PDPN and low-PDPN groups. The high-PDPN group tended to have more diffuse-type disease (P= 0.079), which was further confirmed through logistic regression analysis (P=0.008). Kaplan-Meier survival estimates indicated that the recurrence-free survival rate was significantly lower in the high-PDPN group (P= 0.029). In conclusion, plasma soluble PDPN was demonstrated to be a marker for diffuse gastric cancer and may reflect the prognosis of this disease.

The role of cancer-associated fibroblasts in tumorigenesis of gastric cancer

“… Marker Cell origin Expression level in CAFs Biological functions Effects on GC Refs. α-SMA NFs, pericytes, smooth muscle cells Upregulated (downregulated in prostate cancer) Cell contractility, motility, structure, and integrity Prognostic and postoperative chemotherapy indicator [ 24 ] FSP1 NFs, epithelial cells, endothelial cells Upregulated Cell motility, tissue fibrosis Not known [ 32 ] FAP NFs, quiescent stellate cells, immune cells Upregulated ECM remodeling and fibrogenesis Induce angiogenesis and promote metastasis [ 30 ] Vimentin Endothelial cells Upregulated Cell motility, structure, and integrity Induce EMT and migration [ 33 ] PDGFR NFs, smooth muscle cells, pericytes Upregulated Receptor tyrosine kinase activity Induce EMT and promote metastasis [ 38 ] PDPN Endothelial cells Upregulated Cell motility and adhesion Prognostic indicator [ 34 ] Caveolin-1 NFs, endothelial cells, adipocytes Downregulated Structure component Prognostic indicator and EMT [ 41 ] Meflin undifferentiated mesenchymal stem cells Downregulated maintain the undifferentiated state of MSC Not known [ 40 ] CD10 Breast MSCs, pre-B lymphocytes Upregulated metalloendoprotease Not known [ 43 ] GPR77 Polymorphonuclear neutrophils …”

“…Vimentin is a biomarker of EMT, regulating tissue structure and motion during cell migration, and it has been implicated in CAF motility in GC [ 20 , 33 ]. PDPN + CAFs have also been reported as biomarkers and may reflect the poor prognosis in GC [ 34 ].…”