Prognosis and Sensitivity of Adjuvant Chemotherapy in Mucinous Colorectal Adenocarcinoma without Distant Metastasis

SIMPLE SUMMARY: Although chemotherapy plays an essential role in improving the survival rate of colorectal cancer, it is administered regardless of the histological classification of colorectal cancer. Mucinous adenocarcinoma is the second most common histological subtype of colorectal cancer after adenocarcinoma, accounting for 6–21% of cases. While mucinous adenocarcinoma has several poor clinical prognostic factors, controversy persists regarding its poor survival rate. The results of this study, based on analysis of the National Health Insurance database, demonstrated that mucinous adenocarcinoma has a poor survival rate related to chemoresistance. This occurs owing to the molecular properties of mucinous adenocarcinoma associated with inflammation and epithelial-mesenchymal transition (EMT). EMT, a chemoresistance-inducing pathway, increases with mucinous adenocarcinoma progression. Further studies on the development of personalized chemotherapy focusing on the molecular properties of mucinous adenocarcinoma will help improve the survival rate of patients with colorectal cancer. ABSTRACT: In colorectal cancer, whereas mucinous adenocarcinoma (MAC) has several poor clinical prognostic factors compared to adenocarcinoma (AC), the prognosis of MAC remains controversial. We evaluated the prognosis of MAC without distant metastasis and the effects of adjuvant chemotherapy using health insurance registry data managed by South Korea. Patients with colorectal cancer between January 2014 and December 2016 were included (AC, 22,050 [96.8%]; MAC, 729 [3.2%]). We observed no difference in overall survival (OS) between AC and MAC in stages I and II. However, MAC showed a worse OS than AC in stage III disease, especially in patients administered chemotherapy (p < 0.001). These findings persisted after propensity score matching of clinical characteristics between AC and MAC. In addition, transcriptome analysis of The Cancer Genome Atlas (TCGA) data showed increased chemoresistance-associated pathways in MAC compared to AC. In consensus molecular subtypes (CMS) classification, unlike in AC, CMSs 1, 3, and 4 comprised most of MAC and the proportions of CMSs 3 and 4 increased with stage progression. These results suggest clues to overcome resistance to chemotherapy and develop targeted treatments in MAC.