Abstract
It is meaningful to assess the risk of cancer incidence among patients with precancerous colorectal lesions. Comparing the within-sample relative expression orderings (REOs) of colorectal cancer patients measured by multiple platforms with that of normal colorectal tissues, a qualitative transcriptional signature consisting of 1,840 gene pairs was identified in the training data. Within an evaluation dataset of 16 active and 18 inactive (remissive) ulcerative colitis subjects, the median incidence risk score of colorectal carcinoma was 0.6402 in active ulcerative colitis subjects, significantly higher than that in remissive subjects (0.3114). Evaluation of two other independent datasets yielded similar results. Moreover, we found that the score significantly positively correlated with the degree of dysplasia in the case of colorectal adenomas. In the merged dataset, the median incidence risk score was 0.9027 among high-grade adenoma samples, significantly higher than that among low-grade adenomas (0.8565). In summary, the developed incidence risk score could well predict the incidence risk of precancerous colorectal lesions and has value in clinical application.
Highlights
Colorectal cancer (CRC) is one of the commonest malignancies worldwide, with high morbidity and mortality rates (Arnold et al, 2017)
4https://www.kegg.jp/kegg/pathway.html multistep malignant transformation of normal colorectal tissues, we initially identified gene pairs with stable but reversal Relative Expression Ordering (REO) between CRC and normal colorectal tissue samples with a threshold of 90%
The 1,840 gene pairs were selected and the REOs of the selected gene pairs of CRC tissues were defined as the CRC signature that was applied for defining the incidence risk score of precancerous colorectal lesions
Summary
Colorectal cancer (CRC) is one of the commonest malignancies worldwide, with high morbidity and mortality rates (Arnold et al, 2017). The condition mainly develops from malignant transformation of acquired precancerous lesions (Conteduca et al, 2013; Brenner et al, 2014), such as inflammatory bowel disease (IBD) and colorectal adenomas. The proportion of bowel affected by IBD and the severity of inflammation likewise affect CRC risk of patients with IBD (Feagins et al, 2009). Another major type of precancerous colorectal lesions is colorectal adenomas (Conteduca et al, 2013; Brenner et al, 2014). None could accurately assess the risk of cancer incidence among non-cancerous patients with precancerous colorectal lesions. It is of great clinical value to construct a molecular signature to assess the incidence of precancerous colorectal lesions converting to CRC, which could eventually aid in the prevention of CRC occurrence
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