Latent class analysis-derived classification improves the cancer-specific death stratification of molecular subtyping in colorectal cancer.

The molecular subtypes of colorectal cancer (CRC) represent a comprehensive dissection of CRC heterogeneity. However, molecular feature-based classification systems have limitations in accurately prognosticating stratification due to the inability to distinguish cancer-specific deaths. This study aims to establish a classification system that bridges clinical characteristics, cause-specific deaths, and molecular features. We adopted latent class analysis (LCA) on 491,107 first primary CRC patients from the Surveillance, Epidemiology, and End Results (SEER) database to reveal hidden profiles of CRC. The LCA-derived classification scheme was further applied to The Cancer Genome Atlas (TCGA) to assess its effectiveness in improving the accurate stratification of molecular-based subtypes of CRC. Four classes were identified based on latent class analysis integrating demographic and clinicopathological information of CRC patients. The LCA-derived Class 1 (LCAC1) and the LCAC2 showed a high risk of dying from non-CRC, while patients in LCAC3 had a risk of dying from CRC 1.41 times that of LCAC1 (95% confidence interval [CI] = 1.39-1.43). LCAC4 had the lowest probability to die from non-CRC (hazard ratio [HR] = 0.22, 95% CI = 0.21-0.24) compared with LCAC1. Since the LCA-derived classification can identify patients susceptible to CRC-specific death, adjusting for this classification allows molecular-based subtypes to achieve more accurate survival stratification. We provided a classification system capable of distinguish CRC-specific death, which will improve the accuracy of consensus molecular subtypes for CRC patients' survival stratification. Further studies are warranted to confirm the molecular features of LCA-derived classification to inform potential therapeutic strategies and treatment recommendations.