# Prediction of PD-L1 and CD68 in Clear Cell Renal Cell Carcinoma with Green Learning

**Authors:** Yixing Wu, Alexander Shieh, Steven Cen, Darryl Hwang, Xiaomeng Lei, S. J. Pawan, Manju Aron, Inderbir Gill, William D. Wallace, C.-C. Jay Kuo, Vinay Duddalwar

PMC · DOI: 10.3390/jimaging11060191 · Journal of Imaging · 2025-06-10

## TL;DR

This paper introduces a Green Learning framework to predict PD-L1 and CD68 biomarkers in kidney cancer using CT scans, improving accuracy and efficiency.

## Contribution

The novel Green Learning framework improves biomarker prediction from CT scans with enhanced accuracy and interpretability.

## Key findings

- The GL model achieved an MSE of 0.0041 and MAE of 0.0346 for PD-L1 expression prediction in 52 ccRCC patients.
- For TAM population prediction, the model reached an AUROC of 0.85, surpassing the previous benchmark of 0.81.
- The framework uses radiomic features processed through DFT, RFT, and LNT for robust biomarker approximation.

## Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. Extensive efforts have been made to utilize radiomics from computed tomography (CT) imaging to predict tumor immune microenvironment (TIME) measurements. This study proposes a Green Learning (GL) framework for approximating tissue-based biomarkers from CT scans, focusing on the PD-L1 expression and CD68 tumor-associated macrophages (TAMs) in ccRCC. Our approach includes radiomic feature extraction, redundancy removal, and supervised feature selection through a discriminant feature test (DFT), a relevant feature test (RFT), and least-squares normal transform (LNT) for robust feature generation. For the PD-L1 expression in 52 ccRCC patients, treated as a regression problem, our GL model achieved a 5-fold cross-validated mean squared error (MSE) of 0.0041 and a Mean Absolute Error (MAE) of 0.0346. For the TAM population (CD68+/PanCK+), analyzed in 78 ccRCC patients as a binary classification task (at a 0.4 threshold), the model reached a 10-fold cross-validated Area Under the Receiver Operating Characteristic (AUROC) of 0.85 (95% CI [0.76, 0.93]) using 10 LNT-derived features, improving upon the previous benchmark of 0.81. This study demonstrates the potential of GL in radiomic analyses, offering a scalable, efficient, and interpretable framework for the non-invasive approximation of key biomarkers.

## Linked entities

- **Proteins:** CD274 (CD274 molecule), CD68 (CD68 molecule)
- **Diseases:** clear cell renal cell carcinoma (MONDO:0005005), ccRCC (MONDO:0007763)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}
- **Diseases:** Clear Cell Renal Cell Carcinoma (MESH:D002292), renal cancer (MESH:D007680), TAM (MESH:D020914), tumor (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12194087/full.md

## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12194087/full.md

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Source: https://tomesphere.com/paper/PMC12194087