循环肿瘤细胞分型和RAS/RAF基因检测在结直肠癌中的临床应用价值  被引量:5

Clinical value of circulating tumor cell typing and RAS/RAF gene detection in colorectal cancer

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作  者:黄祥奇 何丹[1] 郭金瑞 崔咏梅 陈健宁[1] 梁静 Huang Xiangqi;He Dan;Guo Jinrui;Cui Yongmei;Chen Jianning;Liang Jing(Department of Pathology,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区:[1]中山大学附属第三医院病理科,广州510630

出  处:《中国医师杂志》2022年第3期366-370,376,共6页Journal of Chinese Physician

基  金:广东省自然科学基金(2017A030310062)。

摘  要:目的探讨结直肠癌(CRC)患者中循环肿瘤细胞(CTC)、RAS/RAF基因突变及其与临床病理特征之间的相关性。方法使用扩增阻滞突变系统-聚合酶链反应(ARMS-PCR)法对中山大学附属第三医院2017年5月至2020年5月收治的138例CRC患者的肿瘤组织行基因突变检测,同时抽取138例患者静脉血经富集后运用mRNA原位杂交技术进行CTC分型检测。分析CTC、RAS/RAF基因突变与CRC患者临床病理特征之间的相关性。结果KRAS、NRAS、BRAF三个基因的突变率分别为48.6%(67/138)、5.1%(7/138)及1.4%(2/138);CTC总体的阳性率是84.1%(116/138),不同型别CTC占比分别为上皮型23.1%(32/138)、混合型71.7%(99/138)、间质型12.3%(17/138)。临床分期Ⅲ~Ⅳ期的CTC阳性率显著高于Ⅰ~Ⅱ期,发生淋巴结转移(N1~N3)的CTC阳性率明显高于无淋巴结转移者(N0),有远处转移(M1)者CTC阳性率高于无远处转移(M0)CTC者,差异有统计学意义(P<0.05)。CTC总数及混合型CTC、间质型CTC与临床分期、淋巴结转移和远处转移均呈正相关(均P<0.05)。RAS/RAF基因突变、性别、年龄、肿瘤位置、肿瘤分化程度均不会影响CTC阳性率(均P>0.05)。结论CTC分型结果对CRC的综合治疗、预后评估和患者分层管理具有十分重要的研究意义,其中间质型CTC可能是导致CRC发生复发转移的一个高危因素。Objective To investigate the correlation between circulating tumor cell(CTC)detection,RAS/RAF gene mutation and clinicopathological characteristics in patients with colorectal cancer(CRC).Methods The Amplification Refractory Mutation System(ARMS)-polymerase chain reaction(PCR)were used to detect the gene mutation in the tumor tissues of 138 CRC patients in the Third Affiliated Hospital of Sun Yat-sen University from May 2017 to May 2020.At the same time,the venous blood of 138 patients was collected and enriched for CTC genotyping by mRNA in situ hybridization.The correlation between CTC,RAS/RAF gene mutation and clinicopathological features of CRC patients was analyzed.Results The mutation rates of KRAS,NRAS and BRAF genes were 48.6%(67/138),5.1%(7/138)and 1.4%(2/138),respectively;The overall positive rate of CTC was 84.1%(116/138).The positive rates of different CTC types were:23.1%(32/138)in epithelial type,71.7%(99/138)in mixed type and 12.3%(17/138)in interstitial type respectively.The positive rate of CTC in CRC patients with clinical stageⅢ-Ⅳ,lymph node metastasis(N1-N3)and distant metastasis(M1)was significantly higher than that in CRC patients with stageⅠ-Ⅱ,no lymph node metastasis(N0)and no distant metastasis(M0)(all P<0.05).The total number of CTC,mixed CTC and interstitial CTC were positively correlated with clinical stage,lymph node metastasis and distant metastasis(all P<0.05).RAS/RAF gene mutation,gender,age,tumor location and tumor differentiation did not affect the positive rate of CTC(all P>0.05).Conclusions The results of CTC typing are of great research significance for comprehensive treatment,prognosis assessment and stratified management of CRC,among which the interstitial type of CTC may be a high risk factor for the recurrence and metastasis of CRC.

关 键 词:结直肠肿瘤 肿瘤细胞 循环 基因 ras 基因 raf 突变 

分 类 号:R735.34[医药卫生—肿瘤]

 

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