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循環(huán)腫瘤細(xì)胞計(jì)數(shù)及分型與頭頸部鱗癌臨床特征的相關(guān)性研究

發(fā)布時(shí)間:2019-06-20 01:21
【摘要】:[目的]研究頭頸部鱗狀細(xì)胞癌(Head and Neck Squamous Cell Carcinoma,HNSCC)患者外周血中循環(huán)腫瘤細(xì)胞(Circulating tumor cells,CTCs)的數(shù)目及各表型數(shù)目與頭頸部鱗癌原發(fā)腫瘤臨床病理特征的關(guān)系。[方法]選取40例HNSCC患者及4例健康志愿者在首次住院時(shí)抽取靜脈血10ml,采用CanpatrolTM CTCs檢測(cè)技術(shù),首先將紅細(xì)胞從外周血中裂解出,再通過根據(jù)CTCs與白細(xì)胞的大小差異采用納米技術(shù),進(jìn)行CTCs分離和富集。CTCs分型和鑒定方案為:使用新型多重mRNA原位分析(multiple mRNA in situ analysis, MRIA)方法,對(duì)富集的CTCs進(jìn)行特異性基因核酸定位,從而對(duì)CTCs進(jìn)行分型和鑒定。研究CTCs計(jì)數(shù)與HNSCC患者性別、有無吸煙飲酒史、分化程度、腫瘤分期、遠(yuǎn)處轉(zhuǎn)移的關(guān)系;各表型與HNSCC分期的關(guān)系。[結(jié)果]1、HNSCC患者的CTCs檢出陽性率為82.50% (33/40),健康者未檢測(cè)到CTCs。CTCs檢測(cè)與病理診斷的一致性檢驗(yàn)結(jié)果顯示:二者具有中等的一致性(K=0.462,P0.0001)。有吸煙飲酒史CTCs計(jì)數(shù)高于無吸煙史患者具有統(tǒng)計(jì)學(xué)意義(P=0.0467)。2、不同T分期患者CTCs計(jì)數(shù)差別具有統(tǒng)計(jì)學(xué)意義(P0.005) ; pT4期的CTCs計(jì)數(shù)明顯高于pT1~pT3期(P0.005);患者CTCs計(jì)數(shù)與T分期具有正相關(guān)關(guān)系(P0.001);颊逤TCs計(jì)數(shù)與N分期的相關(guān)關(guān)系有統(tǒng)計(jì)學(xué)意義(P=0.0051)。不同臨床分期患者的CTCs陽性檢出率之間差異具有統(tǒng)計(jì)學(xué)意義(P=0.025),臨床分期越高,CTCs檢測(cè)陽性率有升高趨勢(shì);不同臨床分期患者CTCs計(jì)數(shù)差別具有統(tǒng)計(jì)學(xué)意義(P=0.0002),Ⅳ期患者的CTCs計(jì)數(shù)明顯高于Ⅱ期、Ⅲ期,患者CTCs計(jì)數(shù)與臨床分期具有正相關(guān)關(guān)系(P=0.0343)。3、不同分化程度患者CTCs陽性檢出率之間差異具有統(tǒng)計(jì)學(xué)意義(P=0.025),分化程度越低,CTCs檢測(cè)陽性率有升高趨勢(shì)。不同分化程度患者CTCs計(jì)數(shù)差別具有統(tǒng)計(jì)學(xué)意義(P0.0001),低分化組患者的CTCs計(jì)數(shù)明顯高于中、高分化的患者,中分化組患者的CTCs計(jì)數(shù)明顯高于高分化的患者,患者CTCs計(jì)數(shù)與分化程度具有負(fù)相關(guān)關(guān)系(P0.0001),CTCs計(jì)數(shù)隨分化程度的升高而降低。4、上皮型CTCs數(shù)量在臨床分期之間具有統(tǒng)計(jì)學(xué)差異(P=0.0258);混合型CTCs數(shù)量在臨床分期之間具有統(tǒng)計(jì)學(xué)差異(P=0.0223)。33例HNSCC不同臨床分期的各型別CTCs檢出率比較,Ⅱ、Ⅲ、Ⅳ期的上皮型CTCs檢出率差別有統(tǒng)計(jì)學(xué)差別(p=0.042),陽性檢出率隨臨床分期增高而降低;Ⅱ、Ⅲ、Ⅳ期的混合型CTCs檢出率差別無統(tǒng)計(jì)學(xué)差別(P=0.224),臨床分期升高混合型CTCs檢出率有升高趨勢(shì);Ⅱ、Ⅲ、Ⅳ期的間質(zhì)型CTCs檢出率差別無統(tǒng)計(jì)學(xué)差別(p=0.065),間質(zhì)型CTCs檢出率以Ⅳ期最高(76.48%)。5、3例病情進(jìn)展出現(xiàn)遠(yuǎn)處轉(zhuǎn)移患者的CTCs數(shù)量明顯高于37例無進(jìn)展遠(yuǎn)處轉(zhuǎn)移的患者,兩者具有統(tǒng)計(jì)學(xué)差異(P=0.0001);有、無進(jìn)展患者的CTCs數(shù)量差別有統(tǒng)計(jì)學(xué)意義(P=0.0005)。CTCs數(shù)量預(yù)測(cè)HNSCC遠(yuǎn)處轉(zhuǎn)移患者的ROC曲線下面積為0.9640 (0.8918-1.036),具有統(tǒng)計(jì)學(xué)意義(P=0.0082);CTCs數(shù)量預(yù)測(cè)HNSCC病情進(jìn)展患者的ROC曲線下的面積為0.8673(0.7137-1.021),有統(tǒng)計(jì)學(xué)意義(P=0.0055)。[結(jié)論]1、HNSCC患者血液循環(huán)中確實(shí)存在著惡性腫瘤細(xì)胞的浸潤(rùn),CTCs檢測(cè)可輔助診斷HNSCC。2、CTCs計(jì)數(shù)與HNSCC患者的T分期、分化程度、臨床分期密切相關(guān);患者CTCs計(jì)數(shù)與T分期、臨床分期具有正相關(guān)關(guān)系,患者CTCs計(jì)數(shù)與分化程度具有負(fù)相關(guān)關(guān)系。復(fù)發(fā)轉(zhuǎn)移HNSCC患者CTCs計(jì)數(shù)較無復(fù)發(fā)轉(zhuǎn)移患者高。3、HNSCC患者均可檢測(cè)到上皮型、混合型、間質(zhì)型CTCs,且各型別CTCs與臨床分期密切相關(guān),早期以上皮型CTCs為主;晚期患者以混合型、間質(zhì)型CTCs為主。4、CTCs有可能成為HNSCC輔助早期診斷、提高臨床分期準(zhǔn)確性、指導(dǎo)治療決策和復(fù)發(fā)轉(zhuǎn)移風(fēng)險(xiǎn)預(yù)測(cè)的指標(biāo)。
[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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