Abstract
Accurate risk stratification for patients with stage II/III colon cancer is pivotal for postoperative treatment decisions. Here, we aimed to identify and validate a circRNA‐based signature that could improve postoperative prognostic stratification for these patients. In current retrospective analysis, we included 667 patients with R0 resected stage II/III colon cancer. Using RNA‐seq analysis of 20 paired frozen tissues collected postoperation, we profiled differential circRNA expression between patients with and without recurrence, followed by quantitative validation. With clinical information, we generated a four‐circRNA‐based cirScore to classify patients into high‐risk and low‐risk groups in the training cohort. The patients with high cirScores in the training cohort had a shorter disease‐free survival (DFS) and overall survival (OS) than patients with low cirScores. The prognostic capacity of the classifier was validated in the internal and external cohorts. Loss‐of‐function assays indicated that the selected circRNAs played functional roles in colon cancer progression. Overall, our four‐circRNA‐based classifier is a reliable prognostic tool for postoperative disease recurrence in patients with stage II/III colon cancer.
Highlights
60% of patients with colon cancer present with stage II/III disease (Rabeneck et al, 2015)
We developed and validated a novel prognostic tool based on four circRNAs to improve the prognostic stratification for patients with radically resected stage II/III colon cancer
Our results showed that this tool can effectively classify patients with stage II/III colon cancer into groups with low and high risks of disease recurrence
Summary
60% of patients with colon cancer present with stage II/III disease (Rabeneck et al, 2015). Clinicopathological risk factors and microsatellite instability status do not adequately distinguish between patients who have a high or low risk of disease recurrence, thereby not indicating which patients are likely to benefit from postoperative chemotherapy (Gray et al, 2007; Morris et al, 2007). In view of this clinical challenge, there is an unmet need for novel recurrence-specific molecular biomarkers that allow for better prognostic stratification and more appropriate therapies for patients with stage II/III colon cancer
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