Identification of Potential Biomarkers and Biological Pathways for Poor Clinical Outcome in Mucinous Colorectal Adenocarcinoma

SIMPLE SUMMARY: Patients with mucinous adenocarcinoma (MAC) have been considered to have a faster disease progression than patients with traditional adenocarcinoma (TAC) in colorectal cancer (CRC). However, to date, the roles of MAC in long-term survival remain controversial due to a small sample size and the nature of its relatively rare occurrence, although it potentially represents entities with different aggressiveness and prognoses. Here, using large-scale population data, we found that the patients with the MAC subtype had a significantly worse overall survival rate and a tendency of worse disease-specific survival rate in stage II compared with the patients with the TAC subtype. Furthermore, key gene signatures were identified using the established predictive models for the disease-specific survival of stage II mucinous CRC. ABSTRACT: Colorectal cancer (CRC) comprises several histological subtypes, but the influences of the histological subtypes on prognosis remains unclear. We sought to evaluate the prognosis of mucinous adenocarcinoma (MAC), compared to that of traditional adenocarcinoma (TAC). This study used the data of patients diagnosed with CRC between 2004 and 2016, as obtained from the Surveillance, Epidemiology, and End Results database. We established a predictive model for disease-specific survival using conditional survival forest, model, non-linear Cox proportional hazards, and neural multi-task logistic regression model and identified the gene signatures for predicting poor prognosis based on the arrayexpress datasets. In total, 9096 (42.1%) patients with MAC and 12,490 (58.9%) patients with TAC were included. Those with the MAC subtype were more likely to have a poorer overall survival rate compared to those with the TAC subtype in stage II CRC (p = 0.002). The eight major genes including RPS18, RPL30, NME2, USP33, GAB2, RPS3A, RPS25, and CEP57 were found in the interacting network pathway. MAC was found to have a poorer prognosis compared to TAC, especially in Stage II CRC. In addition, our findings suggest that identifying potential biomarkers and biological pathways can be useful in CRC prognosis.