Gene Expression Profile Reveals a Prognostic Signature of Non-MSI-H/pMMR Colorectal Cancer.

Studies have demonstrated that non-MSI-H/pMMR colorectal cancer (CRC) has a worse prognosis and relapse rate than microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) CRC. Hence, searching for a novel tool to advance the prognostic management of non-MSI-H/pMMR CRC is vital. In this study, using three independent public cohorts and a clinical in-house cohort, we developed and validated a microsatellite stable-associated signature (MSSAS). The initial signature establishment was performed in GSE39582 ( = 454). This was followed by independent validation of this signature in The Cancer Genome Atlas-CRC ( = 312), GSE39084 ( = 54), and in-house cohort ( = 146). As a result, MSSAS was proven to be an independent risk factor for overall survival and relapse-free survival in non-MSI-H/pMMR CRC. Receiver operating characteristic analysis showed that MSSAS had a stable and accurate performance in all cohorts for 1, 3, and 5 years, respectively. Further analysis suggested that MSSAS performed better than age, gender, and the T, N, M, and AJCC stages, adjuvant chemotherapy, tumor mutation burden, neoantigen, and 53, , , and mutations. The clinical validation was executed to further ensure the robustness and clinical feasibility of this signature. In conclusion, MSSAS might be a robust and promising biomarker for advancing clinical management of non-MSI-H/pMMR CRC.