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循环肿瘤细胞计数及分型与头颈部鳞癌临床特征的相关性研究

发布时间:2019-06-20 01:21
【摘要】:[目的]研究头颈部鳞状细胞癌(Head and Neck Squamous Cell Carcinoma,HNSCC)患者外周血中循环肿瘤细胞(Circulating tumor cells,CTCs)的数目及各表型数目与头颈部鳞癌原发肿瘤临床病理特征的关系。[方法]选取40例HNSCC患者及4例健康志愿者在首次住院时抽取静脉血10ml,采用CanpatrolTM CTCs检测技术,首先将红细胞从外周血中裂解出,再通过根据CTCs与白细胞的大小差异采用纳米技术,进行CTCs分离和富集。CTCs分型和鉴定方案为:使用新型多重mRNA原位分析(multiple mRNA in situ analysis, MRIA)方法,对富集的CTCs进行特异性基因核酸定位,从而对CTCs进行分型和鉴定。研究CTCs计数与HNSCC患者性别、有无吸烟饮酒史、分化程度、肿瘤分期、远处转移的关系;各表型与HNSCC分期的关系。[结果]1、HNSCC患者的CTCs检出阳性率为82.50% (33/40),健康者未检测到CTCs。CTCs检测与病理诊断的一致性检验结果显示:二者具有中等的一致性(K=0.462,P0.0001)。有吸烟饮酒史CTCs计数高于无吸烟史患者具有统计学意义(P=0.0467)。2、不同T分期患者CTCs计数差别具有统计学意义(P0.005) ; pT4期的CTCs计数明显高于pT1~pT3期(P0.005);患者CTCs计数与T分期具有正相关关系(P0.001)。患者CTCs计数与N分期的相关关系有统计学意义(P=0.0051)。不同临床分期患者的CTCs阳性检出率之间差异具有统计学意义(P=0.025),临床分期越高,CTCs检测阳性率有升高趋势;不同临床分期患者CTCs计数差别具有统计学意义(P=0.0002),Ⅳ期患者的CTCs计数明显高于Ⅱ期、Ⅲ期,患者CTCs计数与临床分期具有正相关关系(P=0.0343)。3、不同分化程度患者CTCs阳性检出率之间差异具有统计学意义(P=0.025),分化程度越低,CTCs检测阳性率有升高趋势。不同分化程度患者CTCs计数差别具有统计学意义(P0.0001),低分化组患者的CTCs计数明显高于中、高分化的患者,中分化组患者的CTCs计数明显高于高分化的患者,患者CTCs计数与分化程度具有负相关关系(P0.0001),CTCs计数随分化程度的升高而降低。4、上皮型CTCs数量在临床分期之间具有统计学差异(P=0.0258);混合型CTCs数量在临床分期之间具有统计学差异(P=0.0223)。33例HNSCC不同临床分期的各型别CTCs检出率比较,Ⅱ、Ⅲ、Ⅳ期的上皮型CTCs检出率差别有统计学差别(p=0.042),阳性检出率随临床分期增高而降低;Ⅱ、Ⅲ、Ⅳ期的混合型CTCs检出率差别无统计学差别(P=0.224),临床分期升高混合型CTCs检出率有升高趋势;Ⅱ、Ⅲ、Ⅳ期的间质型CTCs检出率差别无统计学差别(p=0.065),间质型CTCs检出率以Ⅳ期最高(76.48%)。5、3例病情进展出现远处转移患者的CTCs数量明显高于37例无进展远处转移的患者,两者具有统计学差异(P=0.0001);有、无进展患者的CTCs数量差别有统计学意义(P=0.0005)。CTCs数量预测HNSCC远处转移患者的ROC曲线下面积为0.9640 (0.8918-1.036),具有统计学意义(P=0.0082);CTCs数量预测HNSCC病情进展患者的ROC曲线下的面积为0.8673(0.7137-1.021),有统计学意义(P=0.0055)。[结论]1、HNSCC患者血液循环中确实存在着恶性肿瘤细胞的浸润,CTCs检测可辅助诊断HNSCC。2、CTCs计数与HNSCC患者的T分期、分化程度、临床分期密切相关;患者CTCs计数与T分期、临床分期具有正相关关系,患者CTCs计数与分化程度具有负相关关系。复发转移HNSCC患者CTCs计数较无复发转移患者高。3、HNSCC患者均可检测到上皮型、混合型、间质型CTCs,且各型别CTCs与临床分期密切相关,早期以上皮型CTCs为主;晚期患者以混合型、间质型CTCs为主。4、CTCs有可能成为HNSCC辅助早期诊断、提高临床分期准确性、指导治疗决策和复发转移风险预测的指标。
[Abstract]:[Objective] To study the relationship between the number of circulating tumor cells (CTCs) in peripheral blood of head and neck squamous cell carcinoma (HNSCC) and the clinical and pathological characteristics of head and neck squamous cell carcinoma. [Methods] 40 patients with HNSCC and 4 healthy volunteers were selected to extract 10 ml of venous blood at the first time of hospitalization. The red blood cells were first lysed from the peripheral blood, and the CTCs were separated and enriched by using the nano-technology according to the difference in the size of the CTCs and the white blood cells. The type and identification of CTCs were as follows: the method of multiple mRNA in situ analysis (MRIA) was used to locate the specific gene of CTCs, and the CTCs were classified and identified. The relationship between the number of CTCs and the sex of the HNSCC patients, the history of smoking, the degree of differentiation, the stage of the tumor and the distant metastasis were studied. The relationship between the phenotype and the HNSCC stage was studied. [Results] 1. The positive rate of CTCs in the patients with HNSCC was 82.50% (33/40), and no CTCs were detected in the healthy subjects. The results of the consistency of the detection and the pathological diagnosis of CTCs showed that the positive rate of CTCs was moderate (K = 0.462, P.0001). The number of CTCs in patients with smoking history was higher than that of non-smoking history patients (P = 0.0467). The difference of CTCs in patients with different T staging was statistically significant (P = 0.005), and the CTCs in the pT4 stage were significantly higher than that in pT1 to pT3 (P 0.05), and the count of CTCs in the patients was positively correlated with T stage (P 0.001). The correlation between the count of CTCs and the N staging of patients was statistically significant (P = 0.0051). There was a significant difference in the positive rate of CTCs in patients with different clinical stages (P = 0.025). The higher the clinical stage, the positive rate of CTCs in the patients with different clinical stages was higher. The difference of CTCs in patients with different clinical stages was of statistical significance (P = 0.0002), and the count of CTCs in patients with stage 鈪,

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