Integrated Transcriptomic-proteomic Biomarker Identification for Radiation Response Prediction in Non-small Cell Lung Cancer Cell Lines

To develop an integrated transcriptome-proteome framework for identifying concurrent biomarkers predictive of radiation response, as measured by survival fraction at 2 Gy (SF2), in non-small cell lung cancer (NSCLC) cell lines. RNA sequencing (RNA-seq) and data-independent acquisition mass spectrometry (DIA-MS) proteomic data were collected from 73 and 46 NSCLC cell lines, respectively. Following preprocessing, 1,605 shared genes were retained for analysis. Feature selection was performed using least absolute shrinkage and selection operator (Lasso) regression with a frequency-based ranking criterion under five-fold cross-validation repeated ten times. Support vector regression (SVR) models were constructed using transcriptome-only, proteome-only, and combined transcriptome-proteome feature sets. Model performance was assessed by the coefficient of determination (R2) and root mean square error (RMSE). Correlation analyses evaluated concordance between RNA and protein expression and the relationships of selected biomarkers with SF2. RNA-protein expression exhibited significant positive correlations (median Pearson's r = 0.363). Independent pipelines identified 20 prioritized gene signatures from transcriptomic, proteomic, and combined datasets. Models trained on single-omic features achieved limited cross-omic generalizability, while the combined model demonstrated balanced predictive accuracy in both datasets (R2=0.461, RMSE=0.120 for transcriptome; R2=0.604, RMSE=0.111 for proteome). This study presents the first proteotranscriptomic framework for SF2 prediction in NSCLC, highlighting the complementary value of integrating transcriptomic and proteomic data. The identified concurrent biomarkers capture both transcriptional regulation and functional protein activity, offering mechanistic insights and translational potential.