Glycodelin: A New Biomarker with Immunomodulatory Functions in Non–Small Cell Lung Cancer

Abstract

Purpose: In recent years, immune therapeutic strategies against non–small cell lung cancer (NSCLC) based on tissue-derived biomarkers, for example PD1/PD-L1 (CD274), have evolved as novel and promising treatment options. However, the crosstalk between tumor and immune cells is poorly understood. Glycodelin (gene name PAEP), initially described in the context of pregnancy and trophoblastic implantation, is a secreted immunosuppressive glycoprotein with an as-of-yet largely unknown function in lung cancer. Experimental Design: In this study, we characterized the expression and role of glycodelin in NSCLC through mRNA and protein expression analyses, functional knockdown experiments, and correlations with clinicopathologic parameters. Results: Glycodelin mRNA expression was significantly elevated in tumors (n = 336) compared with matched normal tissue (P < 0.0001). Overall survival (OS) was significantly reduced in NSCLC with high glycodelin mRNA levels in women but not in men. Glycodelin was detected in the sera of patients, and the levels correlated with recurrence and metastatic disease. Knockdown of glycodelin with siRNAs in NSCLC cell lines resulted in significant upregulation of immune system modulatory factors such as PDL1, CXCL5, CXCL16, MICA/B, and CD83 as well as proliferation stimulators EDN1 and HBEGF. Furthermore, decreased migration of tumor cells was observed. Conclusions: Altogether, the comprehensive characterization of glycodelin in NSCLC provides strong support for its use as a biomarker with immune modulatory function. Clin Cancer Res; 21(15); 3529–40. ©2015 AACR.

AURKA, DLGAP5, TPX2, KIF11 and CKAP5: Five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients

“…Total RNA was transcribed to sscDNA with a Transcriptor First Strand cDNA Synthesis kit (Roche Diagnostics GmbH, Mannheim, Germany). More detailed information is described elsewhere (27). …”

“…CT values were calculated with the LightCycler ® 480 software version 1.5 using the 2nd derivative maximum method (Roche Diagnostics). Detailed information is described elsewhere (27). …”

Glycodelin is a potential novel follow-up biomarker for malignant pleural mesothelioma

“…While the polyclonal antibody stained nearly all tumor cells, the immunosuppressive form glycodelin A was only partly and inhomogeneously expressed within the tumor nests (see enlarged areas). Antibody specificity was tested and validated in controls (Figure S2) and elsewhere [29]. …”

“…In a previous study, we showed that glycodelin was expressed in NSCLC tumors and can be used as a biomarker for monitoring of the tumor burden during the therapy [28]. …”

“…In recent years, data have shown an involvement of glycodelin in several tumors including ovarian cancer, breast cancer, and melanoma [25–27]. Glycodelin mRNA was overexpressed in non-small cell lung cancer (NSCLC) and considered a useful serum biomarker for monitoring the clinical follow-up of treated patients [28]. The purpose of the current study was to investigate whether glycodelin is expressed and secreted by MPM and whether it might be used as a novel biomarker for early diagnosis of MPM and monitoring of tumor response to treatment.…”