彭方興,袁三英,吳宸,陳進(jìn),羅亮,陳匯
(綿陽市四〇四醫(yī)院川北醫(yī)學(xué)院附屬第二醫(yī)院胃腸外科,四川 綿陽 621000)
胃癌患者手術(shù)前后外周血D-二聚體與CA724水平測定及意義
彭方興,袁三英,吳宸,陳進(jìn),羅亮,陳匯
(綿陽市四〇四醫(yī)院川北醫(yī)學(xué)院附屬第二醫(yī)院胃腸外科,四川 綿陽 621000)
目的 測定胃癌患者手術(shù)前后外周血中D二聚體(D-D)、糖類抗原724(CA724)表達(dá)水平,并探討其臨床意義。方法選擇2014年1月至2015年3月在我院胃腸外科接受治療的56例胃癌患者作為胃癌組,另選取56例胃良性病變患者和56例健康體檢者分別納入胃良性病變組及健康對照組。比較各組受檢者的D-D及CA724水平,分析胃癌患者病理指標(biāo)與D-D及CA724水平的關(guān)系,以及影響胃癌患者D-D及CA724水平升高的相關(guān)因素。結(jié)果治療前,胃癌組及胃良性病變組患者的D-D及CA724水平均明顯高于健康對照組,且胃癌組患者的D-D及CA724水平明顯高于胃良性病變組,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05);治療后,胃癌組患者的D-D及CA724水平仍明顯高于健康對照組,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05),而胃良性病變組患者的D-D及CA724水平與健康對照組相比,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05);胃癌漿膜層浸潤的患者D-D及CA724水平均明顯高于固有層及肌層浸潤者,有淋巴結(jié)轉(zhuǎn)移的患者D-D及CA724水平均明顯高于無淋巴結(jié)轉(zhuǎn)移者,低分化者D-D及CA724水平均明顯高于中、高分化者,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05);將胃癌患者D-D及CA724水平升高作為因變量,將漿膜層浸潤和有淋巴結(jié)轉(zhuǎn)移,以及低分化作為自變量,實(shí)施Logistic回歸分析發(fā)現(xiàn),漿膜層浸潤和有淋巴結(jié)轉(zhuǎn)移,以及低分化均為胃癌患者D-D及CA724水平升高的相關(guān)因素(P<0.05)。CA724以6.90 U/mL為臨界值時(shí),單獨(dú)CA724監(jiān)測胃癌的敏感度、準(zhǔn)確度均為83.93%,D-D以0.50 mg/L為臨界值時(shí),單獨(dú)CA724監(jiān)測胃癌的敏感度、準(zhǔn)確度均為82.21%,當(dāng)D-D及CA724聯(lián)合監(jiān)測時(shí),其敏感度及準(zhǔn)確度均為96.43%(54/56),提示D-D及CA724聯(lián)合監(jiān)測對于胃癌的診斷價(jià)值明顯高于單獨(dú)D-D及CA724監(jiān)測,差異有統(tǒng)計(jì)學(xué)意義(χ2單獨(dú)D-D=5.973,χ2單獨(dú)CA724=4.940,均P<0.05)。結(jié)論胃癌患者手術(shù)前后監(jiān)測外周血D-D及CA724指標(biāo)水平可較好地反映其疾病情況,值得臨床推薦。
胃癌;外周血;D二聚體;糖類抗原724;測定;臨床意義
胃癌是一種十分常見的惡性腫瘤,由其導(dǎo)致的死亡率在癌癥中位居首位。對于胃癌標(biāo)志物的研究,以往較為注重癌胚抗原(CEA)等指標(biāo),雖然亦可在一定程度上反映患者的病情,但敏感度仍有待提高[1]。近年來,國外有報(bào)道稱,外周血中D二聚體(D-D)及糖類抗原724(CA724)聯(lián)合檢測可能對胃癌診斷鑒別更具價(jià)值[2]。鑒于國內(nèi)在此方面的報(bào)道極少,本文展開研究,旨在為胃癌的治療提供參考依據(jù)。
1.1 一般資料 選擇2014年1月至2015年3月在我院胃腸外科接受治療的56例胃癌患者作為研究對象。所有患者均符合WHO關(guān)于胃癌的臨床診斷標(biāo)準(zhǔn)[3],并經(jīng)影像學(xué)手段檢測證實(shí)。56例患者中男性34例,女性22例;年齡38~68歲,平均(62.3±3.6)歲;管狀腺癌8例,乳頭狀腺癌26例,黏液腺癌15例,印戒細(xì)胞癌7例。所有患者均接受胃癌根治術(shù)治療,術(shù)后4周后開始行化療治療,化療時(shí)間為4~8周。另選56例胃良性病變患者和56例健康體檢者分別納入胃良性病變組及健康對照組。其中胃良性病變組中男性32例,女性24例;年齡35~66歲,平均(61.9±2.8)歲;胃炎46例,胃潰瘍10例。健康對照組中男性30例,女性26例;年齡35~67歲,平均(61.7±3.2)歲。各組受檢者在性別和年齡等方面比較差異均無統(tǒng)計(jì)學(xué)意義(P>0.05),具有可比性。
1.2 研究方法 各組受試者在治療前及治療后12周(健康對照組在體檢時(shí)測定)采集血液標(biāo)本6 mL,使用產(chǎn)于德國的羅氏E170型電化學(xué)發(fā)光儀測定CA724指標(biāo)水平。所用試劑均是羅氏原裝試劑,其中CA724的正常參考值范圍為<6.90 U/mL。使用Sysmex CA-7000全自動(dòng)血凝分析儀(日本希森美康公司)檢測D-D水平,其中D-D的正常參考值范圍為<0.50 mg/L。將手術(shù)病理檢查作為金標(biāo)準(zhǔn),分析胃癌患者D-D及CA724水平監(jiān)測價(jià)值,計(jì)算聯(lián)合監(jiān)測的敏感度及準(zhǔn)確度。
1.3 觀察指標(biāo) 比較各組受試者的D-D及CA724水平,分析胃癌患者病理指標(biāo)與D-D及CA724水平的關(guān)系,以及影響胃癌患者D-D及CA724水平升高的相關(guān)因素。
1.4 統(tǒng)計(jì)學(xué)方法 應(yīng)用SPSS13.0統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)分析,計(jì)數(shù)數(shù)據(jù)比較采用χ2檢驗(yàn),計(jì)量數(shù)據(jù)以均數(shù)±標(biāo)準(zhǔn)差(±s)表示,組間比較采用t檢驗(yàn),采用Logistic回歸法分析影響因素,以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2.1 各組受檢者的D-D和CA724水平比較 治療前胃癌組及胃良性病變組的D-D及CA724水平均顯著高于健康對照組,且胃癌組的D-D及CA724水平顯著高于胃良性病變組,差異均有統(tǒng)計(jì)學(xué)意義(均P<0.05),治療后胃癌組的D-D及CA724水平顯著高于健康對照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05),而胃良性病變組的D-D及CA724水平與健康對照組比較差異無統(tǒng)計(jì)學(xué)意義(P>0.05),見表1。
表1 各組受檢者D-D和CA724水平比較(±s)
表1 各組受檢者D-D和CA724水平比較(±s)
注:與治療前比較,t胃癌組D-D=142.76,t胃癌組CA724=26.32,t胃良性病變組D-D=44.56,t胃良性病變組CA724=7.07,aP<0.05;與健康對照組比較,t胃癌組D-D治療前=157.90,t胃癌組D-D治療后=22.83,t胃良性病變組D-D治療前=54.88;t胃癌組CA724治療前=54.77,t胃癌組CA724治療后=38.59,t胃良性病變組CA724治療前=8.59,bP<0.05。
組別 時(shí)間D-D(mg/L)CA724(U/mL)胃癌組(n=56)胃良性病變組(n=56)健康對照組(n=56)治療前治療后治療前治療后-2.05±0.08b0.42±0.03ab1.13±0.11b0.32±0.08a0.31±0.02 29.46±3.68b14.25±2.27ab3.65±1.02b2.46±0.74a2.42±0.33
2.2 胃癌患者病理指標(biāo)與D-D及CA724水平的關(guān)系 胃癌漿膜層浸潤的患者D-D及CA724水平均顯著高于固有層及肌層浸潤者,有淋巴結(jié)轉(zhuǎn)移的患者D-D及CA724水平均顯著高于無淋巴結(jié)轉(zhuǎn)移者,低分化者D-D及CA724水平均顯著高于中、高分化者,差異均有統(tǒng)計(jì)學(xué)意義(均P<0.05),見表2。
表2 胃癌患者病理指標(biāo)與D-D及CA724水平的關(guān)系(±s)
表2 胃癌患者病理指標(biāo)與D-D及CA724水平的關(guān)系(±s)
注:a表示與漿膜層比較,t固有層D-D=14.97,t肌層D-D=17.16,t固有層CA724=2.48,t肌層CA724=2.04;b表示與無淋巴轉(zhuǎn)移比較,t淋巴轉(zhuǎn)移D-D=7.23,t淋巴轉(zhuǎn)移CA724= 2.15;c表示與低分化相比較,t高分化D-D=2.26,t中分化D-D=2.04,t高分化CA724= 5.23,t中分化CA724=2.10。
病理指標(biāo)CA724(U/mL)分類 例數(shù)D-D(mg/L)浸潤情況27.74±1.33a28.11±2.03a29.08±1.29 27.21±1.58 28.02±1.22b27.09±1.04c28.12±1.58c29.02±1.11固有層肌層漿膜層淋巴轉(zhuǎn)移情況 無有分化情況 高分化中分化低分化7 17 32 21 35 15 21 20 1.74±0.10a1.89±0.03a2.08±0.04 1.91±0.06 2.07±0.09b1.88±0.10c1.92±0.14c2.08±0.33
2.3 影響胃癌患者D-D及CA724水平升高的相關(guān)因素 將胃癌患者D-D及CA724水平升高作為因變量,將漿膜層浸潤和有淋巴結(jié)轉(zhuǎn)移,以及低分化作為自變量,實(shí)施Logistic回歸分析發(fā)現(xiàn),漿膜層浸潤和有淋巴結(jié)轉(zhuǎn)移,以及低分化均為胃癌患者D-D及CA724水平升高的相關(guān)因素,見表3。
表3 影響胃癌患者D-D及CA724水平升高的相關(guān)因素分析
2.4 胃癌患者D-D及CA724水平監(jiān)測價(jià)值 CA724以6.90 U/mL為臨界值時(shí),單獨(dú)CA724監(jiān)測胃癌的敏感度、準(zhǔn)確度均為83.93%,D-D以0.50 mg/L為臨界值時(shí),單獨(dú)CA724監(jiān)測胃癌的敏感度、準(zhǔn)確度均為82.21%,當(dāng)D-D及CA724聯(lián)合監(jiān)測時(shí),其敏感度及準(zhǔn)確度均為96.43%(54/56),提示D-D及CA724聯(lián)合監(jiān)測對于胃癌的診斷價(jià)值明顯高于單獨(dú)D-D及CA724監(jiān)測,差異有統(tǒng)計(jì)學(xué)意義(χ2單獨(dú)D-D=5.973,χ2單獨(dú)CA724= 4.940,均P<0.05),但單獨(dú)D-D及CA724監(jiān)測對于胃癌的診斷價(jià)值基本相同,差異無統(tǒng)計(jì)學(xué)意義(χ2= 0.063,P>0.05),見表4~表6。
表4 胃癌患者CA724水平監(jiān)測價(jià)值(例)
表5 胃癌患者D-D水平監(jiān)測價(jià)值(例)
表6 胃癌患者D-D及CA724水平監(jiān)測價(jià)值(例)
臨床上,胃癌標(biāo)志物主要用于輔助進(jìn)行胃癌診斷或病情監(jiān)測,以往使用較多的是CA125及CA199等指標(biāo)。國外有報(bào)道指出,二者的敏感性及特異性仍不夠理想[4]。近年來,臨床發(fā)現(xiàn),CA724可能對胃癌病情的反映效果更佳,而D-D水平亦逐漸受到人們關(guān)注。鑒于此,本文通過測定胃癌患者的外周血D-D及CA724水平,通過探索其臨床意義以期為更好地監(jiān)測并治療胃癌患者提供數(shù)據(jù)參考支持。
CA724是高分子量的糖蛋白抗原,廣泛存在于機(jī)體的胃部和結(jié)腸以及胰腺等腫瘤中,因此對于監(jiān)測胃癌進(jìn)展情況具有較大價(jià)值[5]。D-D是交朕纖維蛋白形成的一種特異性降解產(chǎn)物,其生成或者增高均反映出凝血及纖溶系統(tǒng)的激活,目前其應(yīng)用巳深入至彌散型血管內(nèi)凝血及心血管疾病亦或是惡性腫瘤等領(lǐng)域[6]。
本文經(jīng)過研究發(fā)現(xiàn),治療前胃癌組及胃良性病變組的D-D及CA724水平均顯著高于健康對照組,且胃癌組的D-D及CA724水平顯著高于胃良性病變組;治療后胃癌組的D-D及CA724水平顯著高于健康對照組,而胃良性病變組的D-D及CA724水平與健康對照組相比,差異無統(tǒng)計(jì)學(xué)意義。提示D-D與CA724指標(biāo)可較好地呈現(xiàn)胃部病變的嚴(yán)重情況[7]。同時(shí),胃部病變尤其是胃癌患者經(jīng)過治療后,D-D及CA724水平均明顯下降,這說明CA724及D-D指標(biāo)水平含量變化可能與胃癌病變機(jī)制具有緊密聯(lián)系,符合Lai等[8]的報(bào)道結(jié)果。此外,本文研究發(fā)現(xiàn),胃癌漿膜層浸潤的患者D-D及CA724水平均顯著高于固有層及肌層浸潤者,有淋巴結(jié)轉(zhuǎn)移的患者D-D及CA724水平均顯著高于無淋巴結(jié)轉(zhuǎn)移者,低分化者D-D及CA724水平均顯著高于中、高分化者。表明D-D及CA724水平均與癌癥浸潤情況和淋巴轉(zhuǎn)移情況以及分化情況呈現(xiàn)出明顯的相關(guān)聯(lián)系[9],進(jìn)一步將胃癌患者D-D及CA724水平升高作為因變量,將漿膜層浸潤和有淋巴結(jié)轉(zhuǎn)移,以及低分化作為自變量,實(shí)施Logistic回歸分析發(fā)現(xiàn),漿膜層浸潤和有淋巴結(jié)轉(zhuǎn)移,以及低分化均為胃癌患者D-D及CA724水平升高的相關(guān)因素。究其原因,筆者認(rèn)為在漿膜層浸潤及低分化方面,腫瘤組織朝器官外不斷浸潤的過程當(dāng)中損傷了正常組織,隨著分化程度的嚴(yán)重,發(fā)生一系列生化改變,進(jìn)而導(dǎo)致D-D及CA724水平增高[10-11]。在有淋巴結(jié)轉(zhuǎn)移方面,主要是因?yàn)榘┌Y轉(zhuǎn)移導(dǎo)致機(jī)體正常組織的破壞,而免疫細(xì)胞發(fā)揮作用時(shí),在免疫反應(yīng)的過程中影響了D-D與CA724的表達(dá)水平。唐菁等[12]亦報(bào)道指出,D-D及CA724聯(lián)合檢測對于胃癌疾病的鑒別價(jià)值較高。本文研究結(jié)果亦顯示,CA724以6.90 U/mL為臨界值時(shí),單獨(dú)CA724監(jiān)測胃癌的敏感度、準(zhǔn)確度均為83.93%,D-D以0.50 mg/L為臨界值時(shí),單獨(dú)CA724監(jiān)測胃癌的敏感度、準(zhǔn)確度均為82.21%,當(dāng)D-D及CA724聯(lián)合監(jiān)測時(shí),其敏感度及準(zhǔn)確度均為96.43%(54/56),提示D-D及CA724聯(lián)合監(jiān)測對于胃癌的診斷價(jià)值明顯高于單獨(dú)D-D及CA724監(jiān)測,基本與之報(bào)道相符。
綜上所述,為胃癌患者監(jiān)測外周血D-D及CA724指標(biāo)水平,可較好地反映其疾病情況,意義重大,值得臨床推薦。
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Determination of peripheral blood D-dimmer and CA724 levels for patients with gastric cancer before and after surgery and its clinical significance.
PENG Fang-xing,YUAN San-ying,WU Chen,CHEN Jin,LUO Liang,CHEN Hui. Department of Gastrointestinal Surgery,the Mianyang No.404 Hospital of Sichuan,Mianyang 621000,Sichuan,CHINA
ObjectiveTo study the expression level of D-dimer(D-D)and carbohydrate antigen 724(CA724) before and after surgery and its clinical significance in peripheral blood of patients with gastric cancer.MethodsFifty-six patients of gastric cancer from January 2014 to March 2015 treated in our hospital were selected as the research subjects(gastric cancer group).Another 56 patients with benign gastric disease and 56 healthy subjects were included in the benign gastric disease group and healthy control group.D-D and CA724 level were compared between the three groups,and the relationship between pathological indexes of gastric cancer and D-D and CA724 levels were analyzed. The related factors of elevated D-D and CA724 levels in patients with gastric cancer were also analyzed.ResultsBefore treatment,D-D and CA724 levels in gastric cancer group and benign gastric disease group were significantly higher than those in healthy control group,and the D-D and CA724 levels in gastric cancer group were significantly higher than those in benign gastric disease group(P<0.05).After treatment,D-D and CA724 levels in gastric cancer group were significantly higher than those in healthy control group(P<0.05),while D-D and CA724 levels in benign gastric disease group showed no significant difference with those in health control group(P>0.05).D-D and CA724 levels in gastric cancer patients with serosa infiltration were significantly higher than those in patients with stroma and myometrial invasion,and the levels were also significantly higher in patients with lymph node metastasis than patients without lymph node metastasis and in patients with poor differentiation than patients with medium or high differentiation(all P<0.05). Taking elevated D-D and CA724 levels in gastric cancer patients as the dependent variable and the serosa invasion, lymph node metastasis,low differentiation as the independent variable,logistic regression analysis showed serosa invasion and lymph node metastasis,and low differentiation were the related factors of elevated D-D and CA724 levels in patients with gastric carcinoma differentiation(P<0.05).The sensitivity and accuracy of gastric cancer was 83.93%, 83.93%for CA724 alone(with CA724 of 6.90 U/mL as the critical value,)and 82.21%,82.21%for D-D alone(with0.50 mg/L as the critical value).For combined detection of D-D and CA724,the sensitivity and accuracy were 96.43% (54/56),96.43%(54/56),which were significantly higher than those for D-D or CA724 alone(χ2D-Dalone=5.973,χ2CA724alone= 4.940,P<0.05).ConclusionMonitoring of D-D and CA724 index in peripheral blood of patients with gastric carcinoma can reflect the disease situation,which is worthy of recommendation.
Gastric cancer;Peripheral blood;D-dimer;Carbohydrate antigen 724;Determination;Clinical significance
R735.2
A
1003—6350(2016)22—3648—04
10.3969/j.issn.1003-6350.2016.22.012
2016-06-13)
四川省教育廳科研項(xiàng)目(編號:12ZB062)
彭方興。E-mail:pfx120@126.com