Abstract

BackgroundCompared with clinically functioning pituitary adenoma (FPA), clinically non-functioning pituitary adenoma (NFPA) lacks of detectable hypersecreting serum hormones and related symptoms which make it difficult to predict the prognosis and monitoring for postoperative tumour regrowth. We aim to investigate whether the expression of selected tumour-related proteins and clinical features could be used as tumour markers to effectively predict the regrowth of NFPA.MethodTumour samples were collected from 295 patients with NFPA from Beijing Tiantan Hospital. The expression levels of 41 tumour-associated proteins were assessed using tissue microarray analyses. Clinical characteristics were analysed via univariate and multivariate logistic regression analyses. Logistic regression algorithm was applied to build a prediction model based on the expression levels of selected proteins and clinical signatures, which was then assessed in the testing set.ResultsThree proteins and two clinical signatures were confirmed to be significantly related to the regrowth of NFPA, including cyclin-dependent kinase inhibitor 2A (CDKN2A/p16), WNT inhibitory factor 1 (WIF1), tumour growth factor beta (TGF-β), age and tumour volume. A prediction model was generated on the training set, which achieved a fivefold predictive accuracy of 81.2%. The prediction ability was validated on the testing set with an accuracy of 83.9%. The area under the receiver operating characteristic curves (AUC) for the signatures were 0.895 and 0.881 in the training and testing sets, respectively.ConclusionThe prediction model could effectively predict the regrowth of NFPA, which may facilitate the prognostic evaluation and guide early interventions.

Highlights

  • Compared with clinically functioning pituitary adenoma (FPA), clinically non-functioning pituitary adenoma (NFPA) lacks of detectable hypersecreting serum hormones and related symptoms which make it difficult to predict the prognosis and monitoring for postoperative tumour regrowth

  • Three proteins and two clinical signatures were confirmed to be significantly related to the regrowth of NFPA, including cyclin-dependent kinase inhibitor 2A (CDKN2A/p16), WNT inhibitory factor 1 (WIF1), tumour growth factor beta (TGF-β), age and tumour volume

  • The prediction model could effectively predict the regrowth of NFPA, which may facilitate the prognostic evaluation and guide early interventions

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Summary

Introduction

Compared with clinically functioning pituitary adenoma (FPA), clinically non-functioning pituitary adenoma (NFPA) lacks of detectable hypersecreting serum hormones and related symptoms which make it difficult to predict the prognosis and monitoring for postoperative tumour regrowth. We aim to investigate whether the expression of selected tumour-related proteins and clinical features could be used as tumour markers to effectively predict the regrowth of NFPA. Few systematic reports have discussed the prediction of the regrowth possibility of NFPA using statistical prediction models. We identified 41 key proteins whose expression were related to tumorigenesis and progression of pituitary adenoma. We established a regrowth prediction model with two clinical signatures and three tumour-associated proteins whose expression levels were varied in NFPA. The main purpose of our study was to determine whether we could build a prediction model and validate its authenticity. Our study may facilitate the prognostic evaluation and early intervention to patients with NFPA

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