An MRI-Based Radiomic Prognostic Index Predicts Poor Outcome and Specific Genetic Alterations in Endometrial Cancer.

Havjin Jacob,Ingfrid S Haldorsen,Sigmund Ytre-Hauge,Kristine E Fasmer,Julie A Dybvik,Camilla Krakstad,Jone Trovik,Erling A Hoivik

doi:10.3390/jcm10030538

Havjin Jacob, Ingfrid S Haldorsen + Show 6 more

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https://doi.org/10.3390/jcm10030538

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Abstract

Integrative tumor characterization linking radiomic profiles to corresponding gene expression profiles has the potential to identify specific genetic alterations based on non-invasive radiomic profiling in cancer. The aim of this study was to develop and validate a radiomic prognostic index (RPI) based on preoperative magnetic resonance imaging (MRI) and assess possible associations between the RPI and gene expression profiles in endometrial cancer patients. Tumor texture features were extracted from preoperative 2D MRI in 177 endometrial cancer patients. The RPI was developed using least absolute shrinkage and selection operator (LASSO) Cox regression in a study cohort (n = 95) and validated in an MRI validation cohort (n = 82). Transcriptional alterations associated with the RPI were investigated in the study cohort. Potential prognostic markers were further explored for validation in an mRNA validation cohort (n = 161). The RPI included four tumor texture features, and a high RPI was significantly associated with poor disease-specific survival in both the study cohort (p < 0.001) and the MRI validation cohort (p = 0.030). The association between RPI and gene expression profiles revealed 46 significantly differentially expressed genes in patients with a high RPI versus a low RPI (p < 0.001). The most differentially expressed genes, COMP and DMBT1, were significantly associated with disease-specific survival in both the study cohort and the mRNA validation cohort. In conclusion, a high RPI score predicts poor outcome and is associated with specific gene expression profiles in endometrial cancer patients. The promising link between radiomic tumor profiles and molecular alterations may aid in developing refined prognostication and targeted treatment strategies in endometrial cancer.

Highlights

We aimed to develop and validate a radiomic prognostic index (RPI) derived from textural features extracted from preoperative magnetic resonance imaging (MRI) and to explore possible associations between the RPI and the corresponding transcriptional profile in endometrial cancer patients
Receiver operating characteristics (ROC) curve of RPI for predicting disease-specific death was plotted and RPI yielded an area under the curve (AUC) of 0.72 (95% confidence interval (CI): 0.58–0.85; p = 0.004) and 0.61 for the patients in the study cohort and MRI validation cohort, respectively
Patients with a high RPI score had significantly poorer 5-year disease-specific survival compared with patients with a low RPI (63% versus 92%, p6 of< 120.001, Figure 2B)

Summary

Introduction

Endometrial cancer is the most common gynecologic malignancy in developed countries. The incidence rate of endometrial cancer has risen steadily during recent years, attributed to increasing obesity and high age in the population [1,2]. Surgicopathological staging according to the International Federation of Gynecology and Obstetrics (FIGO). Staging system and histological subtyping is important for prognostication and guide choice of treatment [3]. Several studies have provided comprehensive molecular characterizations of endometrial cancers [4,5], including The Cancer Genome Atlas (TCGA) project identifying four prognostic groups in endometrial cancer based on gene expression profiles, suggesting a molecular-based reclassification of these tumors [6]

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