AUTHOR=Liu Zaoqu , Xu Hui , Ge Xiaoyong , Weng Siyuan , Dang Qin , Han Xinwei 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.790214

DOI=10.3389/fcell.2022.790214

ISSN=2296-634X

ABSTRACT=<p>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 (<italic>n</italic> = 454). This was followed by independent validation of this signature in The Cancer Genome Atlas–CRC (<italic>n</italic> = 312), GSE39084 (<italic>n</italic> = 54), and in-house cohort (<italic>n</italic> = 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 <italic>TP</italic>53, <italic>KRAS</italic>, <italic>BRAF</italic>, and <italic>PIK3CA</italic> 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.</p>