Prognostic role of molecular subclassification based on mutational profiling and tumor-associated neutrophil status in stage III colon cancer

Abstract

The traditional prognostic prediction of colon cancer (CC) is based on the tumor-node-metastasis (TNM) system. This, however, is not adequate for clinical decision making due to the existence of inter-patient variations and heterogeneity of underlying molecular pathways. We aim to investigate the prognostic value of molecular subclassification utilizing i) tumor-associated neutrophil (TAN) status by immunohistochemical (IHC) staining; ii) microsatellite instability (MSI) and elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) status by PCR-based microsatellite typing; and iii) next-generation sequencing (NGS) mutational profiling by deep sequencing of a 77-gene oncology panel. In the discovery phase, 130 pairs of archived normal and tumor formalin-fixed paraffin-embedded (FFPE) specimens of stage III CC patients were retrospectively recruited from Queen Mary Hospital. CC patients will be categorized into different molecular subclasses (MSCs) based on the status of TAN/MSI/EMAST/NGS mutational profiling molecular biomarkers. Kaplan-Meier analysis, log rank test, univariate and multivariate Cox proportional hazards regression analysis will be used for estimation of progression-free survival (PFS) and overall survival (OS) between the two groups of CC patients. We expect our data to provide useful information for improved stratification of stage III CC patients into high or low risk of recurrence and survival.