Synergizing the interaction of single nucleotide polymorphisms with dosiomics features to build a dual-omics model for the prediction of radiation pneumonitis.

OBJECTIVE

Radiation pneumonitis (RP) is the major dose-limiting toxicity of thoracic radiotherapy. This study aimed to developed a dual-omics (single nucleotide polymorphisms, SNP and dosiomics) prediction model for symptomatic RP.

MATERIALS AND METHODS

The potential SNPs, which are of significant difference between the RP grade ≥ 3 group and the RP grade ≤ 1 group, were selected from the whole exome sequencing SNPs using the Fisher's exact test. Patients with lung cancer who received thoracic radiotherapy at our institution from 2009 to 2016 were enrolled for SNP selection and model construction. The factorization machine (FM) method was used to model the SNP epistasis effect, and to construct the RP prediction model (SNP-FM). The dosiomics features were extracted, and further selected using the minimum redundancy maximum relevance (mRMR) method. The selected dosiomics features were added to the SNP-FM model to construct the dual-omics model.

RESULTS

For SNP screening, peripheral blood samples of 28 patients with RP grade ≥ 3 and the matched 28 patients with RP grade ≤ 1 were sequenced. 81 SNPs were of significant difference (P < 0.015) and considered as potential SNPs. In addition, 21 radiation toxicity related SNPs were also included. For model construction, 400 eligible patients (including 108 RP grade ≥ 2) were enrolled. Single SNP showed no strong correlation with RP. On the other hand, the SNP-SNP interaction (epistasis effect) of 19 SNPs were modeled by the FM method, and achieved an area under the curve (AUC) of 0.76 in the testing group. In addition, 4 dosiomics features were selected and added to the model, and increased the AUC to 0.81.

CONCLUSIONS

A novel dual-omics model by synergizing the SNP epistasis effect with dosiomics features was developed. The enhanced the RP prediction suggested its promising clinical utility in identifying the patients with severe RP during thoracic radiotherapy.