CD109 expression in tumor cells and stroma correlates with progression and prognosis in pancreatic cancer

Abstract

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. High levels of CD109 in tumor cells have been reported to correlate with poor prognosis; however, significance of CD109 stromal expression in human malignancy has not been elucidated. In this study, we investigated the tumorigenic properties of CD109 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis of 92 PDAC surgical specimens revealed that positive CD109 expression in tumor cells was significantly associated with poor prognosis (disease-free survival, p = 0.003; overall survival, p = 0.002), and was an independent prognostic factor (disease-free survival, p = 0.0173; overall survival, p = 0.0104) in PDAC. Furthermore, CD109 expression was detected in the stroma surrounding tumor cells, similar to that of α-smooth muscle actin, a histological marker of cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC (TNM stage, p = 0.033; N factor, p = 0.024; lymphatic invasion, p = 0.028). In addition, combined assessment of CD109 in tumor cells and stroma could identify the better prognosis group of patients from the entire patient population. In MIA PaCa-2 PDAC cell line, we demonstrated the involvement of CD109 in tumor cell motility, but not in PANC-1. Taken together, CD109 not only in the tumor cells but also in the stroma is involved in the progression and prognosis of PDAC, and may serve as a useful prognostic marker in PDAC.

CD109 drives pro-tumorigenic cell properties in human non-small cell lung cancer through interaction with desmoglein-2

“…Among different physiological functions such as protection of stem cells from premature differentiation 4 , detrimental properties have been described mostly linked to tumor biology 47,48 . For some tumor entities, CD109 was suggested as novel clinical biomarker 19 and for LUAD patients CD109 was identified among a cluster of risk genes in patients with poor prognosis 49 . In our study, we can now add another layer of complexity to CD109 in tumor biology of NSCLC.…”

“…In recent years, CD109 emerged as a potential diagnostic biomarker in different cancer entities. These include lung cancer [9][10][11] , breast cancer [12][13][14] , glioma [15][16][17] , and ductal pancreatic adenocarcinoma 18,19 . For some cancer entities, adverse effects for overall patient survival were observed for CD109.…”