Identification of Prognostic Gene Signatures by Developing a scRNA-Seq-Based Integration Approach to Predict Recurrence and Chemotherapy Benefit in Stage II-III Colorectal Cancer

Prospective identification of robust biomarkers related to prognosis and adjuvant chemotherapy has become a necessary and critical step to predict the benefits of adjuvant therapy for patients with stage II-III colorectal cancer (CRC) before clinical treatment. We proposed a single-cell-based prognostic biomarker recognition approach to identify and construct CRC up- and down-regulated prognostic signatures (CUPsig and CDPsig) by integrating scRNA-seq and bulk datasets. We found that most genes in CUPsig and CDPsig were known disease genes, and they had good prognostic abilities in CRC validation datasets. Multivariate analysis confirmed that they were two independent prognostic factors of disease-free survival (DFS). Significantly, CUPsig and CDPsig could effectively predict adjuvant chemotherapy benefits in drug-treated validation datasets. Additionally, they also performed well in patients with CMS4 subtype. Subsequent analysis of drug sensitivity showed that expressions of these two signatures were significantly associated with the sensitivities of CRC cell lines to multiple drugs. In summary, we proposed a novel prognostic biomarker identification approach, which could be used to identify novel prognostic markers for stage II-III CRC patients who will undergo adjuvant chemotherapy and facilitate their further personalized treatments.