Abstract
Simple SummaryAlthough 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.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.
Highlights
Colorectal cancer (CRC) is one of the most common health burdens and the second most frequent cause of cancer-related mortality worldwide [1]
Mucinous adenocarcinoma (MAC) is a histologic subtype defined as adenocarcinoma (AC) with extracellular mucin pools comprising >50% of the tumor volume that occurs in 6~21% of all CRCs [3–5]
While most studies have reported that the prognosis of MAC is worse than that of AC [8–11], large-scale studies showed no difference between the two groups [12,13]
Summary
Colorectal cancer (CRC) is one of the most common health burdens and the second most frequent cause of cancer-related mortality worldwide [1]. Adjuvant chemotherapy plays a significant role in the treatment of CRC, this decision is based solely on the pathologic TNM stage. While most studies have reported that the prognosis of MAC is worse than that of AC [8–11], large-scale studies showed no difference between the two groups [12,13]. One reason for these contradictory results could be the very low incidence of MAC compared to that for AC, making it difficult to reach conclusions. Chemotherapy plays an important role in the prognosis of colorectal cancer, it is often difficult to provide clear information on chemotherapy based on national data [13]
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