消化道恶性肿瘤高通量基因测序的生物统计分析

目的:观察TP53、KRAS、KDR、APC、MLH1及PIK3CA等56个基因在消化道恶性肿瘤中的突变情况，探讨驱动基因的诊疗意义。方法:选择胃食管癌15例、结直肠癌21例患者组织石蜡标本，运用高通量基因测序技术检测56个肿瘤突变高频基因，并进行生物统计分析。结果:36例标本检出34例有已知基因突变，突变基因为TP53、KRAS、MLH1、PIK3CA、KDR、APC、SMARCB1、KIT、EGFR、NRAS、STK11、SMO、SMAD4、CDH1、ERBB2、JAK2和RET共17种。其突变率由高到低依次为:TP53（75.00%），KRAS（33.33%），MLH1、PIK3CA、KDR（均为13.89%），APC（11.76%），SMARCB1（8.82%），KIT、EGFR及NRAS（均为2.78%）。KRAS在结直肠癌中的突变率（47.62%）显著高于在胃食管癌中的突变率（13.33%）。TP53的突变率明显高于其他突变基因。在结直肠癌中KRAS的突变率显著高于KDR、APC、MLH1，未发现有统计学关联。结论:消化道恶性肿瘤TP53突变率较高，可能与病理组织分化程度低及淋巴结转移有关。KRAS在结直肠癌中较在胃食管癌中更易发生突变，存在部位差异。同时KRAS与KDR、APC、MLH1，在结直肠癌患者中存在共突变现象，提示结直肠癌的酪氨酸激酶通路和血管内皮生长因子受体基因在致癌过程中可能存在协同作用，导致肿瘤在结直肠中更易发生发展，选择靶向药物治疗时需考虑协同作用，以便科学精准用药。

Biostatistical analysis of high-throughput gene sequencing for digestive malignant tumors

Objective:To observe the mutation situations of 56 genes such as TP53，KRAS，KDR，APC，MLH1 and PIK3CA in digestive malignant tumors，and explore the diagnosis and treatment significance of driver genes.Methods:Paraffin specimens from 15 cases of gastric cancer，esophageal cancer，21 cases of colorectal cancer were selected，and 56 tumor mutation high-frequency genes were detected by high-throughput gene sequencing，and biological information was analyzed.Results:34 cases with known gene mutations were detected in 36 specimens.The mutant genes were TP53，KRAS，MLH1，PIK3CA，KDR，APC，SMARCB1，KIT，EGFR，NRAS，STK11，SMO，SMAD4，CDH1，ERBB2，JAK2，RET.There were 17 kinds in total.The mutation rate from high to low was as follows: TP53（75.00%），KRAS （33.33%），MLH1，PIK3CA，KDR（all 13.89%），APC（11.76%），SMARCB1 （8.82%），KIT，EGFR,NRAS(all 2.78%).The mutation rate of KRAS in colorectal cancer(47.62%) was significantly higher than that in gastro-esophageal cancer(13.33%).The mutation rate of TP53 was significantly higher than other mutant genes.The mutation rate of KRAS in colorectal cancer was significantly higher than that of KDR，APC，and MLH1，but no statistical correlation was found.Conclusion:The high mutation rate of TP53 in malignant tumors of the digestive tract may be related to the low degree of tissue differentiation and lymph node metastasis in the cases.KRAS is more mutated in the colorectum than in the gastro-esophagus，and there are differences in location.At the same time，KRAS，KDR，APC，and MLH1 have common mutations in colorectal cancer patients，suggesting that the tyrosine kinase pathway of colorectal cancer and the vascular endothelial growth factor receptor gene may have a synergistic effect in the carcinogenic process.The colorectal cancer is more prone to development，and it is necessary to consider synergistic effects when choosing targeted medicines to formulate treatment plans，and to use drugs accurately and reasonably.