# Development of a machine learning model for predicting the expression of proteins associated with targeted therapy in endometrial cancer

**Authors:** Chenwen Sun, Qianling Li, Yanan Huang, Yang Xia, Meiping Li, Xiucong Zhu, Jinke Zhu, Zhenhua Zhao

PMC · DOI: 10.3389/fonc.2025.1502370 · Frontiers in Oncology · 2026-01-12

## TL;DR

This study develops a machine learning model to predict protein expression in endometrial cancer patients using MRI and clinical data, aiming to improve personalized treatment.

## Contribution

A novel machine learning model combining MRI radiomics and clinicopathological features to predict protein expression linked to targeted therapy in endometrial cancer.

## Key findings

- Combination models outperformed radiomic or clinicopathologic models alone in predicting PTEN, PIK3CA, and mTOR expression.
- Calibration and decision curve analyses confirmed the clinical utility and accuracy of the combination models.
- The model shows potential as a tool for personalized adjuvant therapy in endometrial cancer patients.

## Abstract

To develop a machine learning model integrates multi-parametric magnetic resonance imaging (MRI) radiomics features and clinicopathological features to predict the expression status of phosphatase and tension homolog (PTEN), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and mammalian target of rapamycin (mTOR), which are frequently linked with targeted therapy for endometrial cancer (EC), in order to establish a dependable foundation for personalized adjuvant therapy for EC patients.

we retrospectively recruited 82 EC patients who underwent preoperative MRI and radical resection at two independent hospitals. 60 patients from Center 1 were utilized as the training set for constructing the machine learning model, while 22 patients from Center 2 served as an external validation set to assess the model’s performance. We evaluated the performance of models predicted three proteins’ expression using receiver operating characteristic (ROC) analysis, calibration curve analysis, and decision curve analysis (DCA).

To construct machine learning models for predicting the expression of PTEN, PIK3CA, and mTOR, we respectively screened 5 radiomic and 7 clinicopathologic features, 4 radiomic and 9 clinicopathologic features, and 2 radiomic and 10 clinicopathologic features. The area under the curve (AUC) values of the radscore, clinicopathology, and combination models predicting PTEN expression were 0.875, 0.703, and 0.891 in the training set, and 0.750, 0.844, and 0.833 in the validation set, respectively. The AUC values for the models predicted PIK3CA expression in the training set were 0.856, 0.633, and 0.880, respectively, in the validation set, they were 0.842, 0.667, and 0.825. The AUC of each model for mTOR were 0.896, 0.831, and 0.912 in the training set, and 0.729, 0.847, and 0.829 in the validation set. Calibration curve analysis and DCA showed that the combination models were both well calibrated and clinically useful.

Machine learning models integrating multi-parametric MRI radiomics and clinicopathological features can be a potential tool for predicting PTEN, PIK3CA, and mTOR expression status in EC patients.

## Linked entities

- **Genes:** PTEN (phosphatase and tensin homolog) [NCBI Gene 5728], PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290], MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475]
- **Diseases:** endometrial cancer (MONDO:0002447)

## Full-text entities

- **Genes:** MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, IARS1 (isoleucyl-tRNA synthetase 1) [NCBI Gene 3376] {aka GRIDHH, IARS, ILERS, ILRS, IRS, PRO0785}, PIK3CG (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma) [NCBI Gene 5294] {aka IMD97, PI3CG, PI3K, PI3Kgamma, PIK3, p110gamma}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588] {aka ARO, ARO1, CPV1, CYAR, CYP19, CYPXIX}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}
- **Diseases:** metastases (MESH:D009362), FIGO (MESH:D005831), endometrial carcinogenesis (MESH:D063646), effusions (MESH:D000080324), EC (MESH:D016889), Ovarian metastasis (MESH:D010049), lung adenocarcinoma (MESH:D000077192), breast, lung, glioblastoma, (MESH:D061325), sarcoidosis (MESH:D012507), pancreatic cancers (MESH:D010190), I (MESH:D006969), lymphomas (MESH:D008223), leiomyosarcomas (MESH:D007890), head and neck tumors (MESH:D006258), Vessel carcinoma (MESH:C536223), toxicity (MESH:D064420), cysts (MESH:D003560), cancer (MESH:D009369)
- **Chemicals:** Everolimus (MESH:D000068338), paraffin (MESH:D010232), letrozole (MESH:D000077289)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12832483/full.md

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Source: https://tomesphere.com/paper/PMC12832483