[1]符青云,欧阳小明,郅 程,等.结直肠癌组织EGFR、BRAF及NRAS基因突变检测及临床意义分析[J].医学信息,2022,35(13):83-88.[doi:10.3969/j.issn.1006-1959.2022.13.018]
　FU Qing-yun,OUYANG Xiao-ming,ZHI Cheng,et al.Detection and Clinical Significance of EGFR, BRAF and NRAS Gene Mutations in Colorectal Cancer[J].Medical Information,2022,35(13):83-88.[doi:10.3969/j.issn.1006-1959.2022.13.018]
点击复制

结直肠癌组织EGFR、BRAF及NRAS基因突变检测及临床意义分析()
分享到：

医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
35卷
期数:
2022年13期
页码:
83-88
栏目:
论著
出版日期:
2022-07-01

文章信息/Info

Title:
Detection and Clinical Significance of EGFR, BRAF and NRAS Gene Mutations in Colorectal Cancer
文章编号:
1006-1959（2022）13-0083-06
作者:
符青云; 欧阳小明; 郅 程; 等
（1.江门市五邑中医院病理科，广东 江门 529000；2.广州医科大学附属第二医院病理科，广东 广州 510260）
Author(s):
FU Qing-yun; OUYANG Xiao-ming; ZHI Cheng; et al.
(1.Department of Pathology,Wuyi Traditional Chinese Medicine Hospital,Jiangmen 529000,Guangdon,China;2.Department of Pathology,the Second Affiliated Hospital of Guangzhou Medical University,Guangzhou 510260,Guangdong,China)
关键词:
结直肠癌; EGFR; BRAF; NRAS; 基因突变
Keywords:
Colorectal cancer; EGFR; BRAF; NRAS; Gene mutation
分类号:
R735.3；Q811.4
DOI:
10.3969/j.issn.1006-1959.2022.13.018
文献标志码:
A
摘要:
目的 分析结直肠癌（CRC）患者癌组织中表皮生长因子（EGFR）、致癌同源体B1（BRAF）及神经母细胞瘤RAS病毒癌基因同源物（NRAS）基因突变类型，以及其与临床病理特征和预后生存的关系。方法 选择江门市五邑中医院2017年1月-2018年12月确诊的CRC患者321例。采用实时荧光定量PCR法检测CRC患者组织中EGFR、BRAF和NRAS基因突变情况，分析CRC患者组织中EGFR、BRAF和NRAS基因突变情况；分别比较不同性别、年龄、肿瘤部位、分化程度、淋巴结转移、病理分期3种基因突变类型、突变率；Pearson相关性分析CRC中EGFR、BRAF和NRAS表达的关系，Kaplan-Meier分析3个基因突变对总生存期（OS）和无进展生存期（PFS）的影响。结果 CRC组织EGFR突变率为45.79%，BRAF突变率为7.79%，NRAS突变率为2.18%；EGFR基因突变发生率与性别、分化程度、淋巴结转移、TNM分期有关（P＜0.05）；BRAF基因突变发生率与年龄、淋巴结转移有关（P＜0.05）；NRAS基因突变发生率与年龄、性别、肿瘤部位、分化程度及TNM分期均无关（P＞0.05）；EGFR、BRAF和NRAS在CRC中突变两两之间呈正相关（r=0.468、0.457、0.357，P＜0.05）；EGFR和BRAF野生型患者OS和PFS高于突变型患者（P＜0.05），而NRAS野生型和突变型患者OS和PFS差异无统计学意义（P＞0.05）。结论 CRC中EGFR突变率最高，BRAF突变率次之，NRAS突变率最低，检测EGFR、BRAF和NRAS基因突变情况可在一定程度上判断CRC的发展进程。
Abstract:
Objective To analyze the mutation of EGFR, BRAF and neuroblastoma NRAS genes in colorectal cancer tissues and its relationship with clinicopathological characteristics and prognosis of patients with colorectal cancer.Methods A total of 321 patients with CRC in Wuyi Traditional Chinese Medicine Hospital of Jiangmen from January 2017 to December 2018 were selected.The mutations of EGFR, BRAF and NRAS genes in CRC patients were detected by real-time fluorescence quantitative PCR, and the mutations of EGFR, BRAF and NRAS genes in CRC patients were analyzed. Three kinds of gene mutation types and mutation rates of gender, age, tumor location, differentiation degree, lymph node metastasis and pathological stage were compared; Pearson correlation was used to analyze the relationship between the expressions of EGFR, BRAF and NRAS in CRC, and Kaplan-Meier was used to analyze the effects of three gene mutations on total survival (OS) and progression-free survival (PFS).Results EGFR mutation rate in CRC was 45.79%, BRAF mutation rate was 7.79%, and NRAS mutation rate was 2.18%. The incidence of EGFR gene mutation was related to gender, differentiation, lymph node metastasis and TNM stage (P<0.05); the incidence of BRAF gene mutation was related to age and lymph node metastasis (P<0.05); the incidence of NRAS gene mutation was not correlated with age, gender, tumor location, differentiation degree and TNM stage (P>0.05). EGFR, BRAF and NRAS mutations were positively correlated in CRC (r=0.468, 0.457, 0.357, P<0.05). OS and PFS in EGFR and BRAF wild-type patients were higher than those in mutant patients (P<0.05), there was no significant difference in OS and PFS between NRAS wild-type and mutant patients (P>0.05).Conclusion In CRC, EGFR mutation rate is the highest, followed by BRAF mutation rate, and NRAS mutation rate is the lowest. Detection of EGFR, BRAF and NRAS gene mutation can judge the development process of CRC to a certain extent.

参考文献/References:

[1]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.[2]Mauri G,Sartore-Bianchi A,Russo AG,et al.Early-onset colorectal cancer in young individuals[J].Mol Oncol,2019,13(2):109-131.[3]Liu L,Xie D,Xie H,et al.ARHGAP10 Inhibits the Proliferation and Metastasis of CRC Cells via Blocking the Activity of RhoA/AKT Signaling Pathway[J].Onco Targets Ther,2019,27(12):11507-11516.[4]Sabbah DA,Hajjo R,Sweidan K.Review on Epidermal Growth Factor Receptor (EGFR) Structure, Signaling Pathways, Interactions, and Recent Updates of EGFR Inhibitors[J].Curr Top Med Chem,2020,20(10):815-834.[5]Masood A,Kancha RK,Subramanian J.Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: Focus on afatinib[J].Semin Oncol,2019,46(3):271-283.[6]Guerrera F,Renaud S,Tabbó F,et al.Epidermal growth factor receptor mutations are linked to skip N2 lymph node metastasis in resected non-small-cell lung cancer adenocarcinomas[J].Eur J Cardio-Thorac Surg,2017,51(4):680-688.[7]Dumaz N,Jouenne F,Delyon J,et al.Atypical BRAF and NRAS Mutations in Mucosal Melanoma[J].Cancers (Basel),2019,11(8):1133.[8]尤柱,徐丽莉,李雪芬,等.成釉细胞纤维瘤中BRAF突变基因的检测[J].北京大学学报(医学版),2019,51(1):4-8.[9]沙如拉,李文新.结直肠癌KRAS和NRAS及BRAF基因突变状态分析[J].内蒙古医学杂志,2017,49(1):4-7.[10]Kryczka J,Sochacka E,Papiewska-Paj?諭k I,et al.Implications of ABCC4-Mediated cAMP Eflux for CRC Migration[J].Cancers (Basel),2020,12(12):3547.[11]Cui G,Zhao H,Li L.Long noncoding RNA PRKCQ-AS1 promotes CRC cell proliferation and migration via modulating miR-1287-5p/YBX1 axis[J].J Cell Biochem,2020,121(10):4166-4175.[12]Messersmith WA.NCCN Guidelines Updates: Management of Metastatic Colorectal Cancer[J].J Natl Compr Canc Netw,2019,17(5.5):599-601.[13]Barault L,Veyrie N,Jooste V,et al.Mutations in the RAS- MAPK,PI ( 3 ) K ( phosphatidylinositol-3-OH kinase ) signaling network correlate with poor survival in a population-based series of colon cancers[J].Int J Cancer,2008,122(10):2255-2259.[14]Sigismund S,Avanzato D,Lanzetti L.Emerging functions of the EGFR in cancer[J].Mol Oncol,2018,12(1):3-20.[15]Maraka S,Janku F.BRAF alterations in primary brain tumors[J].Discov Med,2018,26(141):51-60.[16]Qian L,Chen K,Wang C,et al.Targeting NRAS-Mutant Cancers with the Selective STK19 Kinase Inhibitor Chelidonine[J].Clin Cancer Res,2020,26(13):3408-3419.[17]Imyanitov E,Kuligina E.Molecular testing for colorectal cancer: Clinical applications[J].World J Gastrointest Oncol,2021,13(10):1288-1301.[18]Afr?觍s?覾nie VA,Marinca MV,Alexa-Stratulat T,et al.KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer - practical implications for the clinician[J].Radiol Oncol,2019,53(3):265-274.[19]Eskilsson E,R?覬sland GV,Solecki G,et al.EGFR heterogeneity and implications for therapeutic intervention in glioblastoma[J].Neuro Oncol,2018,20(6):743-752.[20]Tumbrink HL,Heimsoeth A,Sos ML.The next tier of EGFR resistance mutations in lung cancer[J].Oncogene,2021,40(1):1-11.[21]Sanz-Garcia E,Argiles G,Elez E,et al.BRAF mutant colorectal cancer: prognosis, treatment, and new perspectives[J].Ann Oncol,2017,28(11):2648-2657.[22]许婷,王晰程,李健,等.BRAFV600E突变型晚期结直肠癌靶向治疗的临床分析[J].临床肿瘤学杂志,2020,25(7):613-618.[23]Di Nicolantonio F,Martini M,Molinari F,et al.Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer[J].J Clin Oncol,2008,26(35):5705-5712.[24]Tol J,Dijkstra JR,Klomp M,et al.Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab[J].European Journal of Cancer,2010,46(11):1997-2009.[25]Li X,Yang T,Li CS,et al.Surface Enhanced Raman Spectroscopy (SERS) for the Multiplex Detection of Braf,Kras,and Pik3ca Mutations in Plasma of Colorectal Cancer Patients [J].Theranostics,2018,8(6):1678-1689.[26]Mody K,Bekaii-Saab T.Clinical Trials and Progress in Metastatic Colon Cancer[J].Surgical Oncology Clinics,2018,27(2):349-365.[27]Tol J,Koopman M,Cats A,et al.Chemotherapy,bevacizumab,and cetuximab in metastatic colorectal cancer[J].New England Journal of Medicine,2009,360(6):563-572.[28]Taieb J,Lapeyre-Prost A,Laurent Puig P,et al.Exploring the best treatment options for BRAF-mutant metastatic colon cancer[J].Br J Cancer,2019,121(6):434-442.[29]Hsu CH,Hsu CW,Hsueh C,et al.Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma[J].Mol Cell Proteomics,2016,15(7):2396-2410.

相似文献/References:

[1]张西园.糖尿病与结直肠癌患者预后相关研究进展[J].医学信息,2018,31(01):55.[doi:10.3969/j.issn.1006-1959.2018.01.020]
　ZHANG Xi-yuan.Research Progress in the Relationship between Diabetes and the Prognosis of Colorectal Cancer[J].Medical Information,2018,31(13):55.[doi:10.3969/j.issn.1006-1959.2018.01.020]
[2]陈学敏,彭 琼.中性粒细胞与淋巴细胞比值联合癌胚抗原对结直肠癌早期诊断的研究[J].医学信息,2019,32(02):75.[doi:10.3969/j.issn.1006-1959.2019.02.022]
　CHEN Xue-min,PENG Qiong.Early Diagnosis of Colorectal Cancer by Neutrophil-lymphocyte Ratio Combined with Carcinoembryonic Antigen[J].Medical Information,2019,32(13):75.[doi:10.3969/j.issn.1006-1959.2019.02.022]
[3]李在明,魏正强.外泌体在结直肠癌中的研究进展[J].医学信息,2019,32(03):42.[doi:10.3969/j.issn.1006-1959.2019.03.014]
　LI Zai-ming,WEI Zheng-qiang.Research Progress of Exosomes in Colorectal Cancer[J].Medical Information,2019,32(13):42.[doi:10.3969/j.issn.1006-1959.2019.03.014]
[4]周玲玲,鞠乐乐,颜 玉.结直肠癌患者手术前后血清IGF-1水平变化及临床价值分析[J].医学信息,2019,32(04):121.[doi:10.3969/j.issn.1006-1959.2019.04.039]
　ZHOU Ling-ling,JU Le-le,YAN Yu.Analysis of Changes and Clinical Value of Serum IGF-1 Levels in Patients with Colorectal Cancer before and after Operation[J].Medical Information,2019,32(13):121.[doi:10.3969/j.issn.1006-1959.2019.04.039]
[5]陈小玉,白 鍊,贺春香.结直肠癌根治手术患者营养状况调查[J].医学信息,2019,32(05):83.[doi:10.3969/j.issn.1006-1959.2019.05.025]
　CHEN Xiao-yu,BAI Lian,HE Chun-xiang.Investigation on Nutritional Status of Patients Undergoing Radical Surgery for Colorectal Cancer[J].Medical Information,2019,32(13):83.[doi:10.3969/j.issn.1006-1959.2019.05.025]
[6]李大略,赵资文,刘兆礼,等.加速康复外科对合并有糖尿病的结直肠癌患者术后炎症反应与营养代谢的影响[J].医学信息,2019,32(07):67.[doi:10.3969/j.issn.1006-1959.2019.07.021]
　LI Da-lue,ZHAO Zi-wen,LIU Zhao-li,et al.Effect of Accelerated Rehabilitation Surgery on Postoperative Inflammatory Response and Nutrient Metabolism in Patients with Colorectal Cancer Complicated with Diabetes[J].Medical Information,2019,32(13):67.[doi:10.3969/j.issn.1006-1959.2019.07.021]
[7]王逸飞,王 志,左宏波,等.伊利替康联合替吉奥在晚期结直肠癌治疗的临床研究[J].医学信息,2019,32(07):158.[doi:10.3969/j.issn.1006-1959.2019.07.049]
　WANG Yi-fei,WANG Zhi,ZUO Hong-bo,et al.Clinical Study of Irinotecan Combined with Tegafur,Gimeracil and Oteracil Porassium Capsulesin the Treatment of Advanced Colorectal Cancer[J].Medical Information,2019,32(13):158.[doi:10.3969/j.issn.1006-1959.2019.07.049]
[8]谢 勇,涂经楷,肖明盛,等.腹腔镜与传统开腹结直肠癌根治术手术效果对比[J].医学信息,2019,32(11):98.[doi:10.3969/j.issn.1006-1959.2019.11.026]
　XIE Yong,TU Jing-kai,XIAO Ming-sheng,et al.Comparative of Laparoscopic and Traditional Open Radical Rectal Cancer Radical Operation[J].Medical Information,2019,32(13):98.[doi:10.3969/j.issn.1006-1959.2019.11.026]
[9]李莎莎,李 芳,王卫峰,等.地中海饮食与结直肠癌的相关研究[J].医学信息,2019,32(15):6.[doi:10.3969/j.issn.1006-1959.2019.15.003]
　LI Sha-sha,LI Fang,WANG Wei-feng,et al.Correlation between Mediterranean Diet and Colorectal Cancer[J].Medical Information,2019,32(13):6.[doi:10.3969/j.issn.1006-1959.2019.15.003]
[10]孙 峰,鲍扬漪,朱 婷,等.晚期结直肠癌抗血管生成靶向治疗研究进展[J].医学信息,2019,32(17):1.[doi:10.3969/j.issn.1006-1959.2019.17.001]
　SUN Feng,BAO Yang-yi,ZHU Ting,et al.Advances in Anti-angiogenesis Targeted Therapy for Advanced Colorectal Cancer[J].Medical Information,2019,32(13):1.[doi:10.3969/j.issn.1006-1959.2019.17.001]

更新日期/Last Update: 1900-01-01