Dynamic contrast-enhanced MRI predicts PTEN protein expression which can function as a prognostic measure of progression-free survival in NPC patients.

Gang Wu,Wenzhu Li,Qianyu Yang,Priya S Balasubramanian,Yu Wu,Kun Liu,Mengsen Li,Junnv Xu,Weiyuan Huang,Mingyue Zhu

doi:10.1007/s00432-021-03764-7

Abstract

The objective of our study was to investigate whether a phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression was associated with dynamic contrast-enhanced MRI (DCE-MRI) parameters and prognosis in nasopharyngeal carcinoma (NPC). Two-hundred-and-forty-five (245) patients with NPC who underwent pretreatment biopsy, expression of PTEN detected by immunohistochemistry of biopsy, and radical intensity-modulated radiation therapy (IMRT) with or without chemotherapy were included. Tumor segmentations were delineated on pretreatment MRI manually. The pharmacokinetic parameters (Ktrans, Kep, Ve, and Vp) derived from dynamic contrast-enhanced MRI (DCE-MRI) using the extended Toft's model within the tumor segmentations were estimated. The following demographics and clinical features were assessed and correlated against each other: gender, age, TNM stage, clinical-stage, Epstein-Barr virus (EBV), pathological type, progression-free survival (PFS), and prognosis status. DCE parameter evaluation and clinical feature comparison between the PTEN positive and negative groups were performed and correlation between PTEN expression with the PFS and prognosis status using Cox regression for survival analysis were assessed. A significantly lower Ktrans and Kep were found in NPC tumors in PTEN negative patients than in PTEN positive patients. Ktrans performed better than Kep in detecting PTEN expression with the ROC AUC of 0.752. PTEN negative was associated with later TNM stage, later clinical-stage, shorter PFS, and worse prognosis. Moreover, N stage, pathological type, Kep, and prognostic status can be considered as independent variables in discrimination of PTEN negative expression in NPCs. PTEN negative indicated a shorter PFS and worse prognosis than PTEN positive in NPC patients. Ktrans and Kep derived from DCE-MRI, which yielded reliable capability, may be considered as potential imaging markers that are correlated with PTEN expression and could be used to predict PTEN expression noninvasively. Combined radiological and clinical features can improve the performance of the classification of PTEN expression.

Highlights

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor located on chromosome band 10q23 that regulates proliferation and differentiation in a variety of cancer cell types, including nasopharyngeal carcinoma (NPC) cells.[1,39]
Based on a previous knowledgebase and the following scientific hypothesis, we aim to explore the value of DCE in differentiating positive or negative PTEN expression in NPC patients and evaluate the correlation of PTEN expression status and clinical prognosis further
All consecutive newly diagnosed NPC patients referred to the Department of Radiotherapy at Hainan General Hospital (The Affiliated Hainan Hospital of Hainan Medical University) between May 2018 and October 2020 were included in this prospective study approved by the hospital IRB (NO.2018025)

Summary

Introduction

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor located on chromosome band 10q23 that regulates proliferation and differentiation in a variety of cancer cell types, including nasopharyngeal carcinoma (NPC) cells.[1,39] This locus encodes a dual-specificity phosphatase, with the PTEN protein has both lipid and protein phosphatase activity at its N-terminal domain, and a Cterminal C2 domain which can control cell migration in a calcium independent manner facilitated by the C-terminal PDZ-binding motif. 40 PTEN contains lipid phosphatase activity that regulates various cellular processes and signaling pathways, such as the induction of apoptosis through phosphatidylinositol 3kinase (PI3K)/Akt pathway inhibition and control of cell adhesion, migration, and tumor invasion, by downregulating the activity of focal adhesion kinases (FAKs).[2,3] PTEN possesses a 50 amino acid Cterminal tail that is nonessential for activity but influences stability and can act to regulate and inhibitPTEN functionality.[41]. 40 PTEN contains lipid phosphatase activity that regulates various cellular processes and signaling pathways, such as the induction of apoptosis through phosphatidylinositol 3kinase (PI3K)/Akt pathway inhibition and control of cell adhesion, migration, and tumor invasion, by downregulating the activity of focal adhesion kinases (FAKs).[2,3] PTEN possesses a 50 amino acid Cterminal tail that is nonessential for activity but influences stability and can act to regulate and inhibit. Knowledge of a tumor possessing PTEN negative acquired mutations, being that this is an indicator of disease severity and progression, could help shape treatment regime

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