仲立新 孫紅輝

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晚期非小細(xì)胞肺癌患者化療過(guò)程中體內(nèi)血漿D-二聚體及纖維蛋白原水平臨床分析

仲立新 孫紅輝

目的 檢測(cè)晚期非小細(xì)胞肺癌(NSCLC)患者化療前和化療過(guò)程中體內(nèi)血漿D-二聚體及纖維蛋白原(fibrinogen,FIB)水平，研究二者濃度變化與化療效果和無(wú)進(jìn)展生存期(progression-free survival,PFS)的關(guān)系。方法 選取晚期非小細(xì)胞肺癌患者120例，收集并記錄患者第1、2、3次化療前血漿D-二聚體及纖維蛋白原水平、腫瘤病理類(lèi)型、分期及無(wú)進(jìn)展期。同時(shí)收集60例健康人員的血漿D-二聚體及纖維蛋白原水平作對(duì)照。結(jié)果 血漿D-二聚體及纖維蛋白原水平的異常升高與晚期非小細(xì)胞肺癌患者的年齡、性別、腫瘤分期及病理類(lèi)型均無(wú)相關(guān)性。對(duì)照組D-二聚體和FIB水平分別為0.47 mg/L和3.76 g/L，明顯低于化療前晚期NSCLC患者的(0.96 mg/L和4.32 g/L)，差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)?；焹蓚€(gè)周期后，有效(PR+SD)的晚期NSCLC患者D-二聚體和FIB水平分別為0.65 mg/L和2.74 g/L，無(wú)效患者分別為1.72 mg/L和4.65 g/L，對(duì)比差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。晚期NSCLC患者的PFS中位數(shù)為5.4個(gè)月，化療前D-二聚體和FIB陰性的患者PFS明顯長(zhǎng)于陽(yáng)性患者，差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。將3次化療前患者的D-二聚體和FIB水平進(jìn)行對(duì)比，雖在不斷降低，但差異無(wú)統(tǒng)計(jì)學(xué)意義(P均>0.05)。結(jié)論 晚期非小細(xì)胞肺癌患者化療前D-二聚體和FIB水平異常升高，能夠提示肺癌的診斷。治療過(guò)程中要監(jiān)測(cè)腫瘤進(jìn)展情況，及時(shí)調(diào)整治療方案，延長(zhǎng)患者PFS。

晚期非小細(xì)胞肺癌；化療；D-二聚體；纖維蛋白原；無(wú)進(jìn)展生存期

(ThePracticalJournalofCancer,2017,32:382～385)

肺癌是最常見(jiàn)的肺原發(fā)性惡性腫瘤，大多數(shù)起源于支氣管黏膜上皮，又稱支氣管肺癌。肺癌的發(fā)病率和死亡率占所有腫瘤之首，吸煙人數(shù)的增加以及工業(yè)的快速發(fā)展對(duì)城市造成的污染都是導(dǎo)致肺癌發(fā)病率不斷升高的主要原因[1-3]。2015年調(diào)查數(shù)據(jù)顯示，全球肺癌新增病人180萬(wàn)，僅我國(guó)就有接近60萬(wàn)的新發(fā)病例。預(yù)計(jì)到2025年，我國(guó)肺癌患者將突破100萬(wàn)，成為世界上肺癌患者最多的國(guó)家[4-5]。肺癌的生存率極低，有研究表明肺癌患者的5年生存率僅為16%。肺癌對(duì)人們的身體健康和生活質(zhì)量都造成了嚴(yán)重的不良影響，因此對(duì)肺癌治療方法的研究成為了醫(yī)療領(lǐng)域熱門(mén)的課題[6-7]。目前在肺癌治療領(lǐng)域我國(guó)已經(jīng)取得了比較大的進(jìn)展，患者的生存率得到了明顯提高，生存質(zhì)量也有所改善。由于肺癌的早期癥狀不明顯，難以發(fā)現(xiàn)，因此如果能夠?qū)υ缙诜伟┗颊哌M(jìn)行有效的評(píng)估與診斷，這對(duì)肺癌的治療具有重要的意義[8-10]。本研究通過(guò)檢測(cè)晚期非小細(xì)胞肺癌患者化療前和化療過(guò)程中體內(nèi)血漿D-二聚體及纖維蛋白原水平，研究二者濃度變化與化療效果和無(wú)進(jìn)展生存期的關(guān)系，探討二者在診斷腫瘤進(jìn)展和預(yù)測(cè)化療效果中的意義。

1 材料與方法

1.1 一般資料

選取2013年1月至2015年12月間在我院住院治療的晚期非小細(xì)胞肺癌患者120例，其中男性80例，女性40例，平均年齡(41.26±3.25)歲，年齡21～58歲。對(duì)照組健康人員60例，男性32例，女性28例，平均年齡(39.75±4.15)歲，年齡18～56歲。兩組年齡、性別間差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。本研究獲我院倫理委員會(huì)批準(zhǔn)，患者或近親屬對(duì)研究方案簽署知情同意書(shū)。

1.2 入選標(biāo)準(zhǔn)

患者年齡>18歲；經(jīng)組織學(xué)或細(xì)胞學(xué)診斷確診為非小細(xì)胞肺癌；處于非小細(xì)胞肺癌晚期；預(yù)計(jì)生存期大于3個(gè)月；無(wú)其他腫瘤及腎類(lèi)疾??；患者自愿參與本次研究。

1.3 排除標(biāo)準(zhǔn)

非晚期肺小細(xì)胞癌患者；病情嚴(yán)重，預(yù)計(jì)生存期較短；除肺癌外患有其他栓塞性疾??；嚴(yán)重的免疫缺陷或自身免疫??；患者不同意參與此次研究。

1.4 化療方法

前兩次化療均進(jìn)行一線化療，第3次化療前通過(guò)影像學(xué)檢查評(píng)估患者腫瘤進(jìn)展及轉(zhuǎn)移情況。

1.5 療效評(píng)定

按照國(guó)際統(tǒng)一標(biāo)準(zhǔn)，療效評(píng)定結(jié)果分為完全緩解(complete response,CR)、部分緩解(partial response,PR)、病情穩(wěn)定(stable disease,SD)及腫瘤進(jìn)展(progress disease,PD)，本次研究中未出現(xiàn)CR現(xiàn)象，因此認(rèn)定PR+SD為有效組，PD為無(wú)效組。有效組患者繼續(xù)進(jìn)行原化療方案，無(wú)效組患者改變治療方案。

1.6 統(tǒng)計(jì)學(xué)方法

應(yīng)用SPSS 20.0統(tǒng)計(jì)學(xué)軟件對(duì)實(shí)驗(yàn)所得所有數(shù)據(jù)進(jìn)行處理和分析，組內(nèi)和組間數(shù)據(jù)比較采用t檢驗(yàn)，P<0.05視為差異具有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 血漿D-二聚體及纖維蛋白原水平與肺癌臨床病理特征的關(guān)系

血漿D-二聚體及纖維蛋白原水平的異常升高與晚期非小細(xì)胞肺癌患者的年齡、性別、腫瘤分期及病理類(lèi)型均無(wú)相關(guān)性，P均>0.05，見(jiàn)表1。

表1 血漿D-二聚體及纖維蛋白原水平與肺癌臨床病理特征關(guān)系/例

2.2 NSCLC組與對(duì)照組D-二聚體和FIB水平比較

對(duì)照組D-二聚體和FIB水平分別為0.47 mg/L和3.76 g/L，明顯低于化療前晚期NSCLC患者的0.96 mg/L和4.32 g/L，差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。

2.3 血漿D-二聚體和FIB水平與化療效果的關(guān)系

化療2個(gè)周期后，有效(PR+SD)的晚期NSCLC患者D-二聚體和FIB水平分別為0.65 mg/L和2.74 g/L，無(wú)效患者為1.72 mg/L和4.65 g/L，對(duì)比差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。

2.4 血漿D-二聚體和FIB陽(yáng)性與PFS的關(guān)系

晚期NSCLC患者的PFS中位數(shù)為5.4個(gè)月，化療前D-二聚體和FIB陰性患者PFS明顯長(zhǎng)于陽(yáng)性患者，差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。

2.5 三次化療前后患者的D-二聚體和FIB水平對(duì)比

將三次化療前患者的D-二聚體和FIB水平進(jìn)行對(duì)比，雖在不斷降低，但差異無(wú)統(tǒng)計(jì)學(xué)意義(P均>0.05)(表2)。

表2 三次化療前后患者的D-二聚體和FIB水平對(duì)比

3 討論

D-二聚體是纖維蛋白單體經(jīng)活化因子X(jué)III交聯(lián)后，再經(jīng)纖溶酶水解所產(chǎn)生的1種特異性降解產(chǎn)物，是1個(gè)特異性的纖溶過(guò)程標(biāo)記物。D-二聚體來(lái)源于纖溶酶溶解的交聯(lián)纖維蛋白凝塊[11-13]。纖維蛋白原是1種由肝臟合成的具有凝血功能的蛋白質(zhì)。纖維蛋白是在凝血過(guò)程中，凝血酶切除血纖蛋白原中的血纖肽A和B而生成的單體蛋白質(zhì)[14-15]。臨床上通過(guò)對(duì)D-二聚體和FIB水平進(jìn)行測(cè)定來(lái)評(píng)價(jià)患者的凝血狀態(tài)，大量研究表明，腫瘤與凝血系統(tǒng)之間存在相互影響作用。因此對(duì)D-二聚體和FIB水平進(jìn)行測(cè)定也可以作為惡性腫瘤診斷的依據(jù)，對(duì)腫瘤的早期治療具有重要意義[16-18]。這一診斷方法目前已經(jīng)被應(yīng)用于對(duì)非小細(xì)胞肺癌的診斷，并且在晚期非小細(xì)胞肺癌的臨床治療中發(fā)揮出巨大作用。

本研究主要檢測(cè)晚期非小細(xì)胞肺癌患者化療前和化療過(guò)程中體內(nèi)血漿D-二聚體及纖維蛋白原水平，研究二者濃度變化與化療效果和無(wú)進(jìn)展生存期的關(guān)系，結(jié)果發(fā)現(xiàn)：血漿D-二聚體及纖維蛋白原水平的異常升高與晚期非小細(xì)胞肺癌患者的年齡、性別、腫瘤分期及病理類(lèi)型均不相關(guān)，P值均大于0.05。對(duì)照組D-二聚體和FIB水平分別為0.47 mg/L和3.76 g/L，明顯低于化療前晚期NSCLC患者的0.96 mg/L和4.32 g/L，差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。進(jìn)行兩個(gè)周期的化療后，有效(PR+SD)的晚期NSCLC患者D-二聚體和FIB水平分別為0.65 mg/L和2.74 g/L，無(wú)效患者為1.72 mg/L和4.65 g/L，對(duì)比差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。晚期NSCLC患者的PFS中位數(shù)為5.4個(gè)月，化療前D-二聚體和FIB陰性的患者PFS明顯長(zhǎng)于呈陽(yáng)性的患者，差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。將三次化療前患者的D-二聚體和FIB水平進(jìn)行對(duì)比，雖在不斷降低，但差異無(wú)統(tǒng)計(jì)學(xué)意義(P均>0.05)。血漿D-二聚體和FIB與腫瘤間存在著互相影響的作用，兩者濃度的異常升高暗示著腫瘤的進(jìn)展情況，因此對(duì)患者血漿D-二聚體和FIB水平的檢測(cè)可以作為晚期非小細(xì)胞肺癌的診斷依據(jù)，這對(duì)患者的早期治療具有重要意義。

綜上所述，晚期非小細(xì)胞肺癌患者化療前D-二聚體和FIB水平異常升高，能夠提示肺癌的診斷。治療過(guò)程中要監(jiān)測(cè)腫瘤進(jìn)展情況，及時(shí)調(diào)整治療方案，延長(zhǎng)患者PFS。

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(編輯：吳小紅)

Clinical Analysis of Plasma D-dimer and Fibrinogen Levels in Patients with Advanced Non-small Cell Lung Cancer During Chemotherapy

ZHONG Lixin，SUN Honghui.

The First People’s Hospital of Nanyang,Nanyang,473010

Objective To study the changes of plasma D-dimer and fibrinogen (FIB) in patients with advanced non-small cell lung cancer (NSCLC) before and after chemotherapy,and to investigate the effect of chemotherapy on the concentration of D-dimer and fibrinogen And progression-free survival (PFS),and to explore their significance in the diagnosis of tumor progression and prognosis of chemotherapy.Methods 120 patients with advanced non-small cell lung cancer (NSCLC) who were hospitalized in our hospital from January 2013 to December 2015 were enrolled in this study.Plasma D-dimer and fibrin were measured before and after the first,Original level,tumor pathological type,stage and no progression.The plasma D-dimer and fibrinogen levels of 60 healthy people were collected as controls,and the relationship between plasma D-dimer and fibrinogen level and the progress of lung cancer and the therapeutic effect were studied.Results Abnormal elevation of plasma D-dimer and fibrinogen levels was not associated with age,sex,tumor stage and pathological type of patients with advanced non-small cell lung cancer,P values were greater than 0.05.The levels of D-dimer and FIB in the control group were 0.47 mg/L and 3.76 g/L,respectively,which were significantly lower than those of the patients with NSCLC before chemotherapy (0.96 mg/L and 4.32 g/L,P<0.05 ).D-dimer and FIB levels were 0.65 mg/L and 2.74 g/L,1.72 mg/L and 4.65 g/L,respectively,in patients with advanced NSCLC who were treated with both cycles of chemotherapy (PR + SD),The difference was statistically significant (P<0.05).In patients with advanced NSCLC,the median PFS was 5.4 months.PFS was significantly longer in D-dimer and FIB-negative patients before chemotherapy than in patients with positive results (P<0.05).The levels of D-dimer and FIB were compared before and after chemotherapy,but the differences were not statistically significant (P>0.05).Conclusion D-dimer and FIB levels in patients with advanced non-small cell lung cancer (NSCLC) are abnormally high before chemotherapy,which may be helpful for the diagnosis of lung cancer.The course of treatment to monitor tumor progression,timely adjustment of treatment programs to extend the patient PFS.

Advanced non-small cell lung cancer;Chemotherapy;D-dimer;Fibrinogen;Progression-free survival

473010 南陽(yáng)市第一人民醫(yī)院

10.3969/j.issn.1001-5930.2017.03.010

R734.2

A

1001-5930(2017)03-0382-04

2016-10-09

2016-11-04)