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【摘要】 目的：探讨可溶性Apo-Ⅰ/Fas(sApo-1/Fas)在女性肺腺癌患者化疗前后血清中的水平及其临床价值。方法：采用酶联免疫吸附试验法(ELISA)对50例宣威女性肺腺癌化疗前后血清sApo-Ⅰ/Fas水平进行测定,并同时检测30例正常人血清sApo-Ⅰ/Fas水平作为对照。结果：肺癌患者血清sApo-Ⅰ/Fas水平明显高于正常对照组(P<0.05),血清sApo-1/Fas水平与临床分期有关、与宣威女性肺癌患者细胞分化程度无关;Ⅳa期肺癌患者血清sApo-1/Fas水平明显高于其它各期(P<0.05),Ⅲb期明显高于Ⅲa及Ⅱb期(P<0.05), Ⅲa期与Ⅱb期比较无显著性差异(P>0.05);分化程度较好(高分化腺癌及中分化腺癌)肺癌患者血清sApo-1/Fas水平,与分化程度较差(低分化腺癌)肺癌患者比较无显著性差异(P>0.05);化疗后有效(完全缓解和部分缓解)患者血清sApo-1/Fas水平明显低于化疗前(P<0.05)。结论：血清sApo-1/Fas的检测对探讨肺癌的病情判断及预后观察有一定价值，以便更好的进行化疗。
【关键词】 可溶性Apo-1/Fas 化疗 肺癌
Serum Soluble Apo-1/Fas changes in patients with lung cancer undergone Chemotherapy and clinical significance
HOU Wen-jun, WANG Qian, WANG Wei-wei, et al
1. Xuanwei people’s hospital, Yunnan 655400, China;
2.The thired affiliated hospital of Kunming medical college
【Abstract】 Objective：To investigate the changes of soluble Apo-1/Fas (sApo-1/Fas) level in female patients who lived in Xuanwei with adenocarcinoma of lung before and after chemotherapy, and its clinical significance. Methods:The level of sApo-1/Fas was measured by enzyme linked immunosorbent assays (ELISA) in 50 female cases of adenocarcinoma of lung that lived in XuanWei before and after chemotherapy, as compared with 30 case of normal control subject.Results: The level of sApo-1/Fas was elevated in all subgroups of female patients who lived in Xuanwei with adenocarcinoma of lung compared to the controls(P<0.05), sApo-1/Fas was correlated with clinical stage, and not with age and histological grade; the sApo-1/Fas level in stageⅣa was higher in comparison with stage Ⅲb、Ⅲa 、and Ⅱb (P<0.05),and in stage Ⅲb it was higher than in stage Ⅲa and Ⅱb(P<0.05); But no significant difference was detected between stageⅢa and Ⅱb (P>0.05), there was no difference between well differentiated, moderately differentiated adenocarcinoma and poorly differentiated Aden carcinoma (P>0.05).That the sApo-1/Fas levels were remarkably reduced in complete remission or partial remission patients (P<0.05) after chemotherapy.Conclusions: Determination of sApo-1/Fas may be useful in the study of judgment of patient’s condition and the observation of prong in female patients who lived in Xuanwei with adenocarcinoma of lung. It is better to guide to chemotherapy.
【Key words】Soluble Apo-1/Fas; Chemotherapy; Lung cancer
肺癌的发病率及死亡率居全世界各种恶性肿瘤的首位,中国云南的宣威市是全国肺癌的高发区，化疗是肺癌治疗的主要方法之一，化疗主要是诱导细胞凋亡，最近有研究发现,凋亡相关因子Apo-Ⅰ/Fas广泛表达于机体多种组织细胞, Apo-Ⅰ/FasL与细胞表面的mApo-Ⅰ/Fas结合后,可诱导表达mApo-Ⅰ/Fas的细胞凋亡。我们通过探讨化疗前后血清sApo-Ⅰ/Fas的变化来说明sApo-Ⅰ/Fas与肺癌的病情、化疗效果及预后的关系。
1 材料与方法
1.1 临床资料
正常对照组35例为健康体检者,均为女性,年龄41～63岁,中位年龄55岁。肺癌组50例,均为宣威女性，年龄40～72岁,中位年龄64岁,均通过电子纤维支气管镜或穿刺病检确诊为肺腺癌，均不能手术。按照1991年制订的国际肺癌TNM分期标准: Ⅱb期9例、Ⅲa期12例、Ⅲb期21例、Ⅳa期8例。病理类型:分化腺癌14例、中分化腺癌19例、低分化腺癌17例。治疗前Karnofsky评分>80分,预计生存期在3个月以上,无过敏体质,心、肾功能和血像正常,均为初次化疗。
1.2 治疗方法
肺癌患者采用NP方案:NVB(长春瑞宾) 25 mg/m2,静脉滴注,第1、8天;DDP(顺铂)30 mg/m2,静脉滴注,第1～3天;每4周为1个周期,每例化疗3个周期以上。
1.3 疗效评价标准
完全缓解(CR):治疗后病灶完全消失,且持续4周以上,无新的病灶出现;部分缓解(PR):病灶缩小50%以上,且持续4周以上,无新的病灶出现;稳定(SD):病灶无明显变化,包括病灶缩小不到50%或增大不超过25%;进展(PD):病灶增大25%以上或出现新的病灶。CR+PR为有效,SD+PD为无效。
1.4 实验方法
晨起空腹抽取静脉血1 ml,1 000 r/min离心10 min,分离出血清,置-70 ℃冰箱保存,采用双抗体夹心ELISA法测定血清sApo-1/Fas水平,试剂购自深圳晶美生物工程公司(美国Genzyme公司产品分装);实验操作严格按说明书要求进行。正常对照组以及大肠癌组分别于化疗前与第2周化疗结束后(14±2)天检测指标。
1.5 统计学分析
各组数据用均数±标准差(x±s)表示,采用方差分析或配对t检验。以P＜0.05 为差异具有显著性。
2 结果
2.1 肺癌各期患者与正常对照组血清sApo-1/Fas水平比较
肺癌患者血清sApo-Ⅰ/Fas水平明显高于正常对照组,有显著性差异(P<0.05)。Ⅳa肺癌患者血清sApo-Ⅰ/Fas水平明显高于其它各期,有非常显著性差异(P<0.05)；Ⅲb期明显高于Ⅲa期及Ⅱb期,有非常显著性差异(P<0.05)；Ⅲa期与Ⅱb期比较无显著性差异(P>0.05),见表1。表1 各期大肠癌患者与正常对照组血清sApo-1/Fas水平比较(略)
2.2 血清sApo-Ⅰ/Fas水平与肺癌患者临床病理特征的关系
血清sApo-Ⅰ/Fas水平与宣威女性肺癌患者年龄无显著相关性(P>0.05);肿瘤细胞分化程度较好(高分化腺癌及中分化腺癌)，肺癌患者血清sApo-Ⅰ/Fas水平与肿瘤细胞分化程度较差(低分化腺癌)肺癌患者比较无显著性差异(P>0.05),说明血清sApo-Ⅰ/Fas水平与肺癌细胞分化程度无关,见表2。表2 血清sApo-Ⅰ/Fas水平与肺癌患者临床病理特征的关系(略)
2.3 近期治疗有效与无效者化疗前后血清sApo-1/Fas水平比较
化疗后有效者血清sApo-Ⅰ/Fas水平明显低于化疗前,有显著性差异(P<0.05);无效者化疗后血清sApo-Ⅰ/Fas水平与化疗前比较无显著性差异(P>0.05),见表3。表3 近期治疗有效与无效者化疗前后血清sApo-1/Fas水平比较(略)
3 讨论
有研究发现［1］,凋亡相关因子Apo-Ⅰ/Fas广泛表达于机体多种组织细胞,尤其是免疫细胞膜表面,包括脾、淋巴结、肺、肾、肝等器官均能持续表达Apo-Ⅰ/Fas；凋亡相关因子Apo-Ⅰ/FasL主要表达于淋巴细胞表面，T细胞表面活化后的Apo-Ⅰ/FasL表达增加［2］。Apo-Ⅰ/Fas/Fas与Apo-Ⅰ/FasL结合是Apo-Ⅰ/Fas在体内发挥作用的惟一途径, Apo-Ⅰ/FasL与细胞表面的mApo-Ⅰ/Fas结合后,可诱导表达mApo-Ⅰ/Fas的细胞凋亡［3］。Apo-Ⅰ/Fas是一缺乏跨膜区的分泌型Apo-Ⅰ/Fas分子,系Apo-Ⅰ/Fas mRNA剪切变异体,称为Apo-1/Fas△TM,缺乏63个核苷酸片段,可编码sApo-1/Fas 3种变异体［4］。目前认为sApo-1/Fas可能通过如下方式介导肿瘤细胞逃避凋亡:①sApo-Ⅰ/Fas竞争性结合Apo-Ⅰ/FasL导致mApo-Ⅰ/Fas与Apo-Ⅰ/FasL相互作用削弱;②mApo-Ⅰ/Fas的缺乏(消除或脱落成为sApo-Ⅰ/Fas)而丧失Apo-Ⅰ/FasL的结合部位［5］。本组研究表明宣威女性肺癌患者血清sApo-1/Fas水平显著高于正常对照组,说明宣威肺腺癌患者与正常人之间血清sApo-1/Fas水平有一定差异,Ⅳa期宣威女性肺腺癌患者血清sApo-1/Fas水平明显高于其它各期,Ⅲb期高于Ⅲa期及Ⅱb期,说明血清sApo-1/Fas水平与肺癌的发展程度相关,sApo-1/Fas水平增高不但可以反映肿瘤负荷、免疫状态及转移状态,而且是免疫细胞的活化标志，
本组的研究也发现,宣威女性肺腺癌患者sApo-1/Fas水平与年龄、细胞分化程度无关。我们的研究亦表明宣威女性肺腺癌化疗有效者血清sApo-1/Fas水平下降,其降低的水平与化疗的近期疗效有一定关系,化疗无效者化疗前后sApo-1/Fas无显著变化，因此,血清sApo-1/Fas水平测定对肺癌的病情判断、化疗效果、预后观察有一定的临床意义。
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作者单位：1.云南省宣威市人民医院外二科，云南 宣威 655400；2.昆明医学院第三附属医院胸外科