Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma
A partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 175 patients atteints d'un carcinome épidermoïde de l'œsophage, cette étude japonaise met en évidence une association entre la surexpression de la protéine glypicane-1 et la chimiorésistance de la tumeur ainsi qu'un pronostic défavorable
Background : Despite the recent improvements in multimodal therapies for oesophageal squamous cell carcinoma (ESCC), the prognosis remains poor. The identification of suitable biomarkers for predicting the prognosis and chemo-sensitivity is required to develop targeted treatments and improve treatment results.
Methods : Proteins highly expressed in ESCC cell lines compared with normal oesophageal cell lines were screened by isobaric tag for relative and absolute quantitation (iTRAQ). We identified glypican-1 (GPC1) as a novel molecule. The clinicopathological characteristics of GPC1 were evaluated by immunohistochemistry using ESCC specimens, and clinical parameters were assessed. The correlation between GPC1 expression levels and chemo-sensitivity were analysed in vitro.
Results : In the immunohistochemical assessment of 175 ESCC patients, 98.8% expressed GPC1. These patients demonstrated significantly poorer prognosis compared with patients with low-GPC1 expression by survival assay (P<0.001). Higher chemoresistance was observed in the GPC1 high-expression group. GPC1 expression levels positively correlated with chemo-sensitivity against cis-Diammineplatinum (II) dichloride (CDDP), and are potentially associated with anti-apoptotic function based on alterations in the MAPK downstream signalling pathway and Bcl-2 family member proteins.
Conclusions : GPC1 is an independent prognostic factor in ESCC and is a critical molecule for altering the threshold of chemoresistance to CDDP.
British Journal of Cancer , résumé, 2015