摘要标题：结直肠腺瘤及腺癌患者血浆游离DNA突变谱特征研究

Background & Aims: This study was designed to explore the plasma cell free DNA (cfDNA) mutation profile in the pathological progression of colorectal cancer. In addition, we aimed to illustrate the difference mutation profile among the left-sided colon, right-sided colon, and rectal carcinoma.

研究背景与目的：本研究探讨在结直肠癌病理进展过程中血浆游离DNA突变谱的变化，并探讨左半结肠，右半结肠，直肠癌的突变谱的差异。

Methods: Tumor tissue and matched blood samples were collected from Henan Provincial People’s Hospital between March 2016 and January 2017.This cohort included 9 cases of colon polyps, 18 cases of colon adenoma, 26 cases of colon cancer, 24 cases of rectal cancer. Tissue DNA, the plasma cfDNA and leukocytes DNA were isolated. The mutation profile of plasma cfDNA in the process of adenoma-to-carcinoma was sequenced using a modified cancer gene panel.

研究方法：纳入2016年3月至2017年1月期间在河南省人民医院接受诊疗的结直肠肿瘤及息肉患者，其中包括9例结肠息肉患者，18例结肠腺瘤患者，26例结肠癌患者，24例直肠癌患者。留取患者肿瘤组织及血样本，分离肿瘤组织DNA,血浆游离DNA，白细胞DNA。采用肿瘤基因捕获测序技术方法对肿瘤组织DNA,血浆游离DNA，白细胞DNA突变谱进行检测分析。

Results: The plasma cfDNA concentrations and somatic mutation burden of colon carcinoma were significantly higher than those in colon polyp and adenoma group. The tumor mutation burden (TMB) in tissue DNA is positively correlated with the TMB in plasma cfDNA. A biomarker combination including the CEA protein level, the plasma cfDNA concentration, and cfDNA mutation burden achieved an area of 0.80 under the receiver operation characteristic curve for diagnosis of CRC. The diagnosis power of the combination model was superior to that of CEA alone. Furthermore,the somatic DNA alteration landscapes are different among the left-sided, right-sided, and rectal cancer. Compared with the life-sided colon, the right-sided colon cancer tumor tissue harbors more gene mutations. And the TMB value of the right-sided colon cancer was significantly higher than those in the life-sided colon and rectal-sided colon cancer (P<0.05).

研究结果：结直肠癌患者的血浆游离DNA浓度及突变负荷显著高于息肉及腺瘤组患者。血浆游离DNA的肿瘤突变负荷（TMB）与肿瘤组织的TMB值呈正相关。联合血浆游离DNA浓度， 血浆游离DNA TMB值，CEA指标联合诊断结直肠癌的ROC曲线下面积可达到0.80，与CEA单指标诊断结直肠癌相比，联合指标诊断可提高ROC曲线下面积。左半结肠，右半结肠，直肠癌的变异谱有显著差异，右半结肠癌的TMB值显著高于左半结肠及直肠癌，右半结肠癌患者出现突变的驱动基因个数增多。

Conclusions: The somatic mutations of plasma cfDNA may be potential biomarkers for diagnosis colorectal cancer. Compared with left-sided colon, the somatic mutations of right-sided colon cancer involved more genes and pathways. 

研究结论：血浆游离DNA突变可能是诊断结直肠癌的潜在标志物；与左半结肠癌相比，右半结肠癌患者突变负荷显著增高。