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Radiomics Features on Magnetic Resonance Images Can Predict C5aR1 Expression Levels and Prognosis in High-Grade Glioma.
Zijun Wu1, Yuan Yang1, and Yunfei Zha1
1Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, China

Synopsis

Keywords: Diagnosis/Prediction, Radiomics, C5aR1; high-grade glioma; MRI; prognosis; biomarker

Motivation: High-grade glioma is a complex disease characterized by genome instability caused by the accumulation of genetic alterations. Identifying and evaluating the oncogenes involved is crucial for determining treatment strategies and evaluating prognosis.

Goal(s): We sought to explore whether radiomics models based on MRI features can noninvasively predict C5aR1 expression and the prognosis of patients with high-grade glioma.

Approach: This study uses machine learning approaches based on paired MRI and RNA sequencing data.

Results: The radiomics models yield satisfactory performances in predicting C5aR1 expression. Our findings also reveal associations between MRI radiomics and immune-related features.

Impact: As an effective and reproducible tool, our radiomics model may support clinical decision making and individualized treatment.

Introduction

The complement component C5a receptor 1 (C5aR1) regulates cancer immunity. This retrospective study aimed to assess its prognostic value in high-grade glioma (HGG) and predict C5aR1 expression using a radiomics approach.

Methods

Among 298 patients with HGG, 182 with MRI data were randomly divided into training and test groups for radiomics analysis. We examined the association between C5aR1 expression and prognosis through Kaplan–Meier and Cox regression analyses. We used maximum relevance–minimum redundancy and recursive feature elimination algorithms for radiomics feature selection. We then built a support vector machine (SVM) and a logistic regression model, investigating their performances using receiver operating characteristic, calibration curves, and decision curves.

Results

C5aR1 expression was elevated in HGG and was an independent prognostic factor (hazard ratio = 3.984, 95% CI: 2.834–5.607). Both models presented with >0.8 area under the curve values in the training and test datasets, indicating efficient discriminatory ability, with SVM performing marginally better. The radiomics score calculated using the SVM model correlated significantly with overall survival (p < 0.01).

Conclusion

Our results highlight C5aR1’s role in HGG development and prognosis, supporting its potential as a prognostic biomarker. Our radiomics model can noninvasively and effectively predict C5aR1 expression and patient prognosis in HGG.

Acknowledgements

Funding: This research was funded by the Fundamental Research Funds for Central Universities (grant number: 2042023kf0036) from Wuhan University.

References

1. Tan, A.C.; Ashley, D.M.; López, G.Y.; Malinzak, M.; Friedman, H.S.; Khasraw, M. Management of glioblastoma: State of the art and future directions. CA Cancer J. Clin. 2020, 70, 299–312. https://doi.org/10.3322/caac.21613.

2. Wen, P.Y.; Weller, M.; Lee, E.Q.; Alexander, B.M.; Barnholtz-Sloan, J.S.; Barthel, F.P.; Batchelor, T.T.; Bindra, R.S.; Chang, S.M.; Chiocca, E.A.; et al. Glioblastoma in adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro-Oncol. 2020, 22, 1073–1113.

3. Ding, P.; Li, L.; Lv, X.; Zhou, D.; Wang, Q.; Chen, J.; Yang, C.; Xu, E.; Dai, W.; Zhang, X.; et al. C5aR1 is a master regulator in Colorectal Tumorigenesis via Immune modulation. Theranostics 2020, 10, 8619–8632.

4. Li, G.; Li, L.; Li, Y.; Qian, Z.; Wu, F.; He, Y.; Jiang, H.; Li, R.; Wang, D.; Zhai, Y.; et al. An MRI radiomics approach to predict survival and tumour-infiltrating macrophages in gliomas. Brain J. Neurol. 2022, 145, 1151–1161.

5. Sun, Q.; Chen, Y.; Liang, C.; Zhao, Y.; Lv, X.; Zou, Y.; Yan, K.; Zheng, H.; Liang, D.; Li, Z.C. Biologic Pathways Underlying Prognostic Radiomics Phenotypes from Paired MRI and RNA Sequencing in Glioblastoma. Radiology 2021, 301, 654–663.

Figures

C5aR1 expression and clinical correlation in HGG according to TCGA. (a) Higher C5areceptor 1 (C5aR1) expression was observed in high-grade glioma (HGG) samples compared withnormal tissues. (b) Correlation of C5aR1 expression with clinicopathologic features. (c) Impact ofC5aR1 expression on overall survival in Kaplan–Meier curves. (d) Time-dependent receiver operatingcharacteristic (ROC) analysis of C5aR1 expression for 1-, 2-, and 3-year survival prediction. *, p < 0.05;**, p < 0.01; ***, p < 0.001.

Prognostic analyses based on the TCGA cohort: (a) Univariate and multivariate Coxregression analysis of C5aR1 and clinicopathologic factors. (b) Subgroup analysis and interaction testfor the prognostic value of C5aR1.

C5aR1-related immune infiltration analysis and pathway enrichment: (a) The differences in the fraction of 22 immune cell types between the high- and low-C5aR1 expression groups from the TCGA cohort. (b) Significantly enriched KEGG pathways and (c) GO annotations of C5aR1-related genes. NS, no significance; *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Radiomics models’ performance in predicting C5aR1 expression for 182 patients with HGG from the TCIA-TCGA intersection cohort: (a,b) ROC curves of the support vector machine (SVM) model in the training and validation cohorts, with (c,d) being the associated SVM calibration and decision curves. (e,f) The logistic regression model ROC curves in the training and validation cohorts, with (g,h) being the accompanying calibration and decision curves.

Analyses of Rad-score based on the TCIA-TCGA intersection cohort: (a) Kaplan–Meier curve showing the association of high radiomics (Rad)-score with worse overall survival of patients and the median survival time in the high- and low-Rad-score groups. (b) The correlations between Rad-score and immune-related genes. (c,d) Difference in C5aR1 expression between high- and low-Rad-score groups in the SVM and LR models, respectively. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.

Proc. Intl. Soc. Mag. Reson. Med. 32 (2024)
3780
DOI: https://doi.org/10.58530/2024/3780