Table_1_Molecular characterization of colorectal adenoma and colorectal cancer via integrated genomic transcriptomic analysis.xlsx

IntroductionColorectal adenoma can develop into colorectal cancer. Determining the risk of tumorigenesis in colorectal adenoma would be critical for avoiding the development of colorectal cancer; however, genomic features that could help predict the risk of tumorigenesis remain uncertain.
MethodsIn this work, DNA and RNA parallel capture sequencing data covering 519 genes from colorectal adenoma and colorectal cancer samples were collected. The somatic mutation profiles were obtained from DNA sequencing data, and the expression profiles were obtained from RNA sequencing data.
ResultsDespite some similarities between the adenoma samples and the cancer samples, different mutation frequencies, co-occurrences, and mutually exclusive patterns were detected in the mutation profiles of patients with colorectal adenoma and colorectal cancer. Differentially expressed genes were also detected between the two patient groups using RNA sequencing. Finally, two random forest classification models were built, one based on mutation profiles and one based on expression profiles. The models distinguished adenoma and cancer samples with accuracy levels of 81.48% and 100.00%, respectively, showing the potential of the 519-gene panel for monitoring adenoma patients in clinical practice.
ConclusionThis study revealed molecular characteristics and correlations between colorectal adenoma and colorectal cancer, and it demonstrated that the 519-gene panel may be used for early monitoring of the progression of colorectal adenoma to cancer.

引言 结直肠腺瘤（colorectal adenoma）可进展为结直肠癌（colorectal cancer）。明确结直肠腺瘤的癌变风险对于预防结直肠癌的发生至关重要，但目前仍未确定可用于预测该癌变风险的基因组特征。
方法 本研究收集了结直肠腺瘤与结直肠癌样本中覆盖519个基因的DNA与RNA平行捕获测序数据。从DNA测序数据中提取体细胞突变谱（somatic mutation profiles），从RNA测序数据中获取基因表达谱（expression profiles）。
结果 尽管腺瘤样本与癌样本存在部分相似性，但结直肠腺瘤与结直肠癌患者的突变谱中，突变频率、突变共现模式与互斥模式均存在差异。通过RNA测序还在两组患者中检测到了差异表达基因。最后，本研究构建了两种随机森林分类（random forest classification）模型：一种基于突变谱，另一种基于表达谱。两种模型区分腺瘤与癌样本的准确率分别为81.48%与100.00%，表明该519基因检测组合（519-gene panel）具备在临床实践中用于监测腺瘤患者的潜力。
结论 本研究揭示了结直肠腺瘤与结直肠癌的分子特征及二者间的关联，并证实该519基因检测组合可用于早期监测结直肠腺瘤向结直肠癌的进展过程。