Laura Gerard, Céline Patte, Laurence Chardon, Valerie Hervieu, Léa Payen, Marion Allio, Claire Marx, Hugo Clermidy, Alice Durand, Patrick Mehlen, Julien Bollard, Gilles Poncet, Colette Roche, Benjamin Gibert, Thomas Walter
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引用次数: 0
Abstract
Neuropilin-2 (NRP2), a transmembrane non-tyrosine kinase receptor, has been described as a potential critical player in the tumourigenesis of several solid cancers, and particularly in neuroendocrine neoplasms (NEN). A soluble form of NRP2 (sNRP2) has been previously described and corresponds to a truncated splice isoform. Its prognostic value has never been studied in NEN. NRP2 expression was studied by immunochemistry on tissue microarrays (n=437) and on circulating tumour cells (CTC, n=5 patients with neuroendocrine carcinoma, NEC). We described the levels of sNRP2 in 229 patients with NEN using the ELISA method to identify the factors associated with sNRP2 levels and to evaluate its prognostic role; 90 blood donors represented the healthy control group. NRP2 was found in 97% of neuroendocrine tumours (396/410) and in 74% of NEC (20/27). NRP2 was also expressed in CTC of all the studied patients. The receiver operating characteristic (ROC) analysis showed that sNRP2 had a weak capacity to discriminate between NEN patients and healthy controls [area under curve (AUC)=0.601, p=0.053]. Abnormal sNRP2 levels were associated with inflammatory syndrome, bone and peritoneal metastases, and abnormal chromogranin A levels. Patients with high sNRP2 levels (sNRP2Q3-Q4) had significantly poorer overall survival in multivariate analysis (HR 0.16, 95%CI [0.04-0.67], p=0.015). In conclusion, the present study found that sNRP2 and NRP2 could represent a new prognostic biomarker and a therapeutic target, respectively, particularly in aggressive NEN.
期刊介绍:
Endocrine-Related Cancer is an official flagship journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology, the United Kingdom and Ireland Neuroendocrine Society, and the Japanese Hormones and Cancer Society.
Endocrine-Related Cancer provides a unique international forum for the publication of high quality original articles describing novel, cutting edge basic laboratory, translational and clinical investigations of human health and disease focusing on endocrine neoplasias and hormone-dependent cancers; and for the publication of authoritative review articles in these topics.
Endocrine neoplasias include adrenal cortex, breast, multiple endocrine neoplasia, neuroendocrine tumours, ovary, prostate, paraganglioma, parathyroid, pheochromocytoma pituitary, testes, thyroid and hormone-dependent cancers. Neoplasias affecting metabolism and energy production such as bladder, bone, kidney, lung, and head and neck, are also considered.