Multiplex Gene Quantification as Digital Cancer Markers for Extremely Rapid Evaluation of Chemodrug Sensitivity

Abstract

In clinical cancer medicine, many patients require immediate chemotherapy after hospitalization. Current administrations for precision drug uses are limited in evaluation speed, including genomic sequencing and tumor organoid evaluation. An extremely rapid evaluation protocol is in high demand to realize drug recommendation within a few hours after tumor sampling. Herein, we propose multiplex gene-based digital cancer markers for personalized drug sensitivity prediction. We first screen cancer transcriptional profiles by applying 2 - 3 gene filters, scoring the genes by their impact on drug sensitivity, and finalise the gene lists by K-nearest-neighbours (KNN) enumeration. The digital markers are cancer type-dependent and composed by assembling predictive genes for individual drugs in clinical uses. The digital markers, comprised of the digital readings of 10s–100s of gene expressions, are rapidly quantified by reverse transcription–quantitative real-time PCR (RT-qPCR) within 1 - 3 hours after cancer sampling. The area under the receiver operating characteristic (ROC) curve (AUC) reached 0.88 when testing the performance of digital markers in patient tumors. An algorithm and its graphic interface were developed to demonstrate the promise of digital cancer markers for extremely rapid drug recommendation.