王剛+呂金燕+王若雨
[摘要] 目的 分析初診肺癌患者血清白細(xì)胞介素-8(IL-8)、趨化因子(Fractalkine)、巨噬細(xì)胞炎性蛋白-3α(MIP-3α)表達(dá)與肺癌臨床特征的相關(guān)性。 方法 回顧性分析大連大學(xué)附屬中山醫(yī)院2013年1月~2015年12月收治的90例初診肺癌患者(初診肺癌組,其中小細(xì)胞癌21例、非小細(xì)胞癌69例)和同期門診體檢結(jié)果無異常的90名健康者(健康組)的臨床資料。首先比較初診肺癌組和健康組血清IL-8、Fractalkine、MIP-3α水平;其次將初診肺癌組患者根據(jù)Ⅰ+Ⅱ期和Ⅲ+Ⅳ期、小細(xì)胞癌和非小細(xì)胞癌進(jìn)行分組,比較血清IL-8、Fractalkine、MIP-3α水平;最后采用Pearson相關(guān)檢驗(yàn)分析初診肺癌組患者血清IL-8、Fractalkine、MIP-3α三個(gè)指標(biāo)之間的相關(guān)性。 結(jié)果 ①初診肺癌組患者血清IL-8、Fractalkine、MIP-3α水平均明顯高于健康組(均P < 0.01)。②Ⅰ+Ⅱ期組患者血清IL-8、Fractalkine、MIP-3α水平均明顯低于Ⅲ+Ⅳ期組(均P < 0.01)。③小細(xì)胞癌組患者血清IL-8、Fractalkine、MIP-3α水平均高于非小細(xì)胞癌組,但差異無統(tǒng)計(jì)學(xué)意義(P > 0.05)。④Pearson相關(guān)分析顯示,IL-8與Fractalkine(r = 0.598,P < 0.05)、IL-8與MIP-3α(r = 0.641,P < 0.05)、Fractalkine與MIP-3α(r = 0.682,P < 0.05)之間均存在線性相關(guān)性。 結(jié)論 初診肺癌患者血清IL-8、Fractalkine、MIP-3α水平高于健康人員,且隨著病情的加重而升高,但不同病理分型之間水平無顯著差異,三個(gè)指標(biāo)相互呈線性相關(guān),可作為初診肺癌患者病情判斷的指標(biāo)。
[關(guān)鍵詞] 肺癌;白細(xì)胞介素-8;Fractalkine;巨噬細(xì)胞炎性蛋白-3α
[中圖分類號(hào)] R734.2 [文獻(xiàn)標(biāo)識(shí)碼] A [文章編號(hào)] 1673-7210(2017)12(b)-0092-04
[Abstract] Objective To analyze the correlation of the expression of serum interleukin-8 (IL-8), chemotactic factor (Fractalkine), macrophage inflammatory protein-3α (MIP-3α) and clinical features of lung cancer in patients with newly diagnosed lung cancer. Methods The clinical data of 90 patients with newly diagnosed lung cancer (newly diagnosed lung cancer group, 21 cases of small cell carcinoma and 69 cases of non small cell carcinoma) admitted to Zhongshan Hospital Affiliated to Dalian University from January 2013 to December 2015 and 90 healthy controls with normal results of outpatient physical examination at the same time (healthy group) was analyzed retrospectively. Firstly, the levels of serum IL-8, Fractalkine, MIP-3α between newly diagnosed lung cancer group and healthy group were compared. Secondly, the newly diagnosed lung cancer group was divided into different groups according to Ⅰ+Ⅱ stage and Ⅲ+Ⅳ stage, small cell carcinoma and non-small cell carcinoma, and the levels of serum IL-8, Fractalkine and MIP-3 were compared. At last, Pearson correlation test was used to analyze the relationship among the levels of serum IL-8, Fractalkine and MIP-3 in newly diagnosed lung cancer group. Results ①The levels of IL-8, Fractalkine, MIP-3α in newly diagnosed lung cancer group were higher than those in healthy group (P < 0.01). ②The levels of IL-8, Fractalkine, MIP-3α in Ⅰ+Ⅱ stage group were lower than those in Ⅲ+Ⅳ stage group (P < 0.01). ③The levels of IL-8, Fractalkine, MIP-3α in small cell carcinoma group were higher than those in non-metastasis group, but the differences were not statistically significant (P > 0.05). ④Pearson correlation analysis showed that there was linear correlation of IL-8 and Fractalkine (r = 0.598, P < 0.05), IL-8 and MIP-3α (r = 0.641, P < 0.05), Fractalkine and MIP-3α (r = 0.682, P < 0.05). Conclusion The levels of IL-8, Fractalkine, MIP-3α in patients with newly diagnosed lung cancer are higher than those of healthy persons, and increase with the escalation of the disease, but there are no significant differences between different pathological types. Three indicators are linearly related to each other and can be used for the condition judgment of patients with newly diagnosed lung cancer.endprint
[Key words] Lung cancer; Interleukin-8; Fractalkine; Macrophage inflammatory protein-3α
我國(guó)每年新發(fā)肺癌患者眾多,肺癌也是導(dǎo)致我國(guó)患者死亡最多的腫瘤,因肺癌死亡患者占所有因癌死亡人數(shù)的近1/5,肺癌已成為我國(guó)重大公共健康問題[1]。既往研究顯示50%以上的初診肺癌患者就診時(shí)至少存在一處轉(zhuǎn)移病灶,病灶的轉(zhuǎn)移導(dǎo)致肺癌患者治療難度增加及病死率增加[2]。如何準(zhǔn)確地在肺癌初診時(shí)即簡(jiǎn)單、有效地評(píng)價(jià)肺癌患者病情對(duì)肺癌后續(xù)治療及降低患者病死率意義重大。對(duì)于隱匿型肺癌轉(zhuǎn)移病灶僅通過影像學(xué)檢查無法完全發(fā)現(xiàn),因此尋找評(píng)價(jià)初診肺癌患者腫瘤細(xì)胞是否轉(zhuǎn)移的方法意義重大。越來越多研究顯示,腫瘤細(xì)胞轉(zhuǎn)移與趨化因子表達(dá)增加關(guān)系密切,趨化因子可能促進(jìn)了肺癌患者的腫瘤轉(zhuǎn)移[3-4]。本研究以90例初診肺癌患者為研究對(duì)象,檢測(cè)其血清白細(xì)胞介素-8(IL-8)、趨化因子(Fractalkine)、巨噬細(xì)胞炎性蛋白-3α(MIP-3α)等因子水平,并分析患者血清IL-8、Fractalkine、MIP-3α與其臨床特征的相關(guān)性,以評(píng)價(jià)趨化因子是否能作為評(píng)價(jià)初診肺癌患者腫瘤病情的潛在指標(biāo),現(xiàn)將結(jié)果報(bào)道如下:
1 資料與方法
1.1 一般資料
對(duì)2013年1月~2015年12月于大連大學(xué)附屬中山醫(yī)院就診的90例初診肺癌患者(初診肺癌組)和同期門診體檢結(jié)果無異常的90名健康者(健康組)進(jìn)行回顧性分析。納入標(biāo)準(zhǔn):①初診肺癌組均符合《原發(fā)性肺癌診療規(guī)范》[5]的診斷標(biāo)準(zhǔn);②初診肺癌組均為首次接受肺癌的診療;③初診肺癌組除原發(fā)性肺癌以外無其他任何腫瘤;④初診肺癌組心、肝、腎等無任何原發(fā)性疾?。虎莩踉\肺癌組和健康組均無感染、免疫方面疾?。虎藿】到M經(jīng)全面體檢均未顯示任何異常結(jié)果。排除標(biāo)準(zhǔn):①不愿參與研究;②臨床資料不全;③健康組患者曾做過肝移植、腎移植等重大手術(shù);④初診肺癌組就診前服用過消炎、鎮(zhèn)痛類的藥物。
初診肺癌組男61例,女29例;平均年齡(54.19±7.60)歲;體重指數(shù)(BMI)(23.15±5.39)kg/m2;發(fā)生淋巴轉(zhuǎn)移者36例,未淋巴轉(zhuǎn)移者54例;TNM分期Ⅰ期12例,Ⅱ期17例,Ⅲ期38例,Ⅳ期23例;病理學(xué)分型:小細(xì)胞癌21例,非小細(xì)胞癌69例。健康組男57名,女33名;平均年齡(53.02±6.18)歲;BMI(24.08±5.42)kg/m2。兩組性別、年齡和BMI等基礎(chǔ)資料比較,差異無統(tǒng)計(jì)學(xué)意義(P > 0.05),具有可比性。
1.2 研究方法
取研究對(duì)象晨起空腹靜脈血15 mL,離心分離血清保存于冰箱中待用,使用酶聯(lián)免疫吸附測(cè)定(ELISA)法檢測(cè)IL-8、Fractalkine、MIP-3α水平,酶聯(lián)免疫分析儀購(gòu)自上海滬試分析儀器有限公司,型號(hào)為MB-602。IL-8:上海心語生物科技有限公司,規(guī)格96T,批號(hào):12060002;Fractalkine試劑盒:上海西唐生物科技有限公司,規(guī)格96T,批號(hào):12090001;MIP-3α:上海潤(rùn)裕生物科技有限公司,規(guī)格48T,批號(hào):12100003。
1.3 觀察指標(biāo)
比較初診肺癌組和健康組血清IL-8、Fractalkine、MIP-3α水平,觀察初診肺癌組和健康組血清中以上因子的水平差異。對(duì)90例初診肺癌組患者根據(jù)Ⅰ+Ⅱ期、Ⅲ+Ⅳ期和小細(xì)胞癌、非小細(xì)胞癌進(jìn)行分組,比較血清IL-8、Fractalkine、MIP-3α的水平。將初診肺癌組患者血清IL-8、Fractalkine、MIP-3α水平進(jìn)行兩兩之間的Pearson相關(guān)分析,分析三個(gè)指標(biāo)之間的相關(guān)性。
1.4 統(tǒng)計(jì)學(xué)方法
用SPSS 14.0統(tǒng)計(jì)軟件對(duì)數(shù)據(jù)進(jìn)行分析,計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,采用t檢驗(yàn),用Pearson線性分析相關(guān)性,以P < 0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 初診肺癌組和健康組血清IL-8、Fractalkine、MIP-3α水平比較
初診肺癌組患者血清IL-8、Fractalkine、MIP-3α水平均顯著高于健康組,差異均有高度統(tǒng)計(jì)學(xué)意義(P < 0.01)。見表1。
2.2 初診肺癌組中Ⅰ+Ⅱ期、Ⅲ+Ⅳ期血清IL-8、Fractalkine、MIP-3α水平比較
初診肺癌組中Ⅰ+Ⅱ期組血清IL-8、Fractalkine、MIP-3α水平均顯著低于Ⅲ+Ⅳ期組,差異均有高度統(tǒng)計(jì)學(xué)意義(P < 0.01)。見表2。
2.3 初診肺癌組不同病理類型血清IL-8、Fractalkine、MIP-3α水平比較
小細(xì)胞癌組患者血清IL-8、Fractalkine、MIP-3α水平均稍高于非小細(xì)胞癌組,但組間差異無統(tǒng)計(jì)學(xué)意義(P > 0.05)。見表3。
2.4 肺癌患者血清IL-8、Fractalkine、MIP-3α水平之間的相關(guān)性
將初診肺癌組患者血清IL-8、Fractalkine、MIP-3α水平進(jìn)行兩兩之間的Pearson相關(guān)分析,結(jié)果顯示IL-8與Fractalkine(r = 0.598,P = 0.042)、IL-8與MIP-3α(r = 0.641,P = 0.037)、Fractalkine與MIP-3α(r = 0.682,P = 0.032)之間均存在線性相關(guān)性。
3 討論
肺癌的轉(zhuǎn)移一直是制約患者治療效果的重要影響因素,如何準(zhǔn)確評(píng)價(jià)初診肺癌淋巴結(jié)轉(zhuǎn)移對(duì)患者預(yù)后意義重大。目前臨床就肺癌轉(zhuǎn)移機(jī)制尚未完全闡明,推測(cè)肺癌轉(zhuǎn)移可能與腫瘤基質(zhì)成分降解、血管生成、腫瘤細(xì)胞變形、趨化因子刺激等多種因素有關(guān)[6-7]。越來越多的證據(jù)表明,趨化因子在肺癌的轉(zhuǎn)移中發(fā)揮重要作用,趨化因子可介導(dǎo)腫瘤細(xì)胞血管生成及內(nèi)皮細(xì)胞增殖,促使腫瘤血管轉(zhuǎn)移[8-9]。另有報(bào)道指出,腫瘤細(xì)胞分泌的趨化因子可刺激腫瘤細(xì)胞免疫耐受,引導(dǎo)腫瘤細(xì)胞經(jīng)淋巴途徑發(fā)生轉(zhuǎn)移[10]。IL-8、Fractalkine、MIP-3α均為重要趨化因子,IL-8可由中性粒、吞噬等多種細(xì)胞分泌,該因子可促進(jìn)內(nèi)皮細(xì)胞增殖,促進(jìn)肺癌腫瘤組織穿梭內(nèi)皮,促進(jìn)腫瘤組織表達(dá)黏附因子,最終促進(jìn)腫瘤穿過血管內(nèi)皮發(fā)生血管途徑的轉(zhuǎn)移[11-12]。多個(gè)動(dòng)物實(shí)驗(yàn)表明,IL-8可促進(jìn)腫瘤細(xì)胞表達(dá)改變,更多表達(dá)侵襲相關(guān)分子,還可促使多種酶活性改變,引發(fā)腫瘤組織轉(zhuǎn)移[13-14]。臨床試驗(yàn)同樣證實(shí)乳腺癌、胃癌等多種癌組織中IL-8含量顯著增加,可達(dá)正常組織的數(shù)倍[15]。endprint
本研究結(jié)果顯示,初診肺癌患者血清IL-8含量明顯高于健康人群,此結(jié)果與國(guó)外相關(guān)研究結(jié)果相符合[16],提示肺癌患者血清IL-8可能與肺癌腫瘤細(xì)胞增殖關(guān)系密切。Fractalkine作為趨化因子,其本質(zhì)是趨化蛋白,該因子主要作用是趨化T細(xì)胞、NK細(xì)胞等多種免疫細(xì)胞黏附,促使腫瘤細(xì)胞免疫耐受,使腫瘤細(xì)胞避免被免疫細(xì)胞殺傷[10]。另有證據(jù)表明Fractal?鄄kine趨化因子是腫瘤細(xì)胞發(fā)生淋巴轉(zhuǎn)移的關(guān)鍵環(huán)節(jié)之一,在腫瘤細(xì)胞的轉(zhuǎn)移中發(fā)揮重要促進(jìn)作用[17-18]。MIP-3α因子表達(dá)的器官較多,肺組織是其主要表達(dá)器官之一,既往基礎(chǔ)研究顯示,MIP-3α的表達(dá)與初診肺癌組織血管生成、腫瘤細(xì)胞侵襲、炎癥介導(dǎo)等關(guān)系密切[19-20]。本研究結(jié)果顯示初診肺癌組患者血清IL-8、Fractalkine、MIP-3α水平均明顯高于健康組,且差異具有顯著性,提示初診肺癌組織促使了血清IL-8、Fractalkine、MIP-3α分泌增加。對(duì)不同分期的初診肺癌患者血清IL-8、Fractalkine、MIP-3α水平進(jìn)行分期,結(jié)果顯示Ⅰ+Ⅱ期組患者血清IL-8、Fractalkine、MIP-3α水均明顯低于Ⅲ+Ⅳ期組(P < 0.05),提示隨著肺癌臨床分期的增加,患者血清IL-8、Fractalkine、MIP-3α水平隨之增加。另采用Pearson檢驗(yàn)對(duì)血清IL-8、Fractalkine、MIP-3α進(jìn)行相關(guān)分析,結(jié)果顯示初診肺癌患者血清IL-8、Fractalkine、MIP-3α相互之間均呈正相關(guān)關(guān)系,提示血清IL-8、Fractalkine、MIP-3α表達(dá)可能具有協(xié)同作用。
綜上所述,初診肺癌患者血清IL-8、Fractalkine、MIP-3α水平高于健康人員,且隨著病情升級(jí)而升高,3個(gè)指標(biāo)相互呈線性相關(guān),可作為初診肺癌患者病情判斷的指標(biāo)。
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(收稿日期:2017-06-14 本文編輯:張瑜杰)endprint