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范杰, 刘冰, 曹文艳, 高卫国. 乳腺癌患者血清抵抗素、脂联素和瘦素水平及其临床意义. 2011, 26(1): 36-39
FAN Jie, LIU Bing, CAO Wenyan, GAO Weiguo. Serum levels of resistin, adiponectin and leptin in breast cancer patients and its clinical significance. Labratory Medicine, 2011, 26(1): 36-39  
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乳腺癌患者血清抵抗素、脂联素和瘦素水平及其临床意义
范杰1, 刘冰2, 曹文艳3, 高卫国1
1.河北工程大学附属医院检验科,河北 邯郸 056029
2.邯郸市第一医院外科,河北 邯郸 056029
3.秦皇岛市中医院检验科,河北 秦皇岛 066000

作者简介:范杰,女,1974年生,主管技师,主要从事临床生化检验工作。

摘要
目的

了解乳腺癌患者血清中抵抗素、脂联素、瘦素及血脂变化及临床意义。

方法

测定90例乳腺癌患者(48例未绝经,42例已绝经)及50名健康对照者血清抵抗素、脂联素、瘦素、空腹血糖(FBG)及血脂。

结果

乳腺癌患者脂联素及高密度脂蛋白胆固醇(HDL-C)显著低于对照组( P<0.01或 P<0.05),抵抗素、瘦素、FBG及三酰甘油(TG)均明显增加( P<0.01或 P<0.05)。但抵抗素、脂联素及瘦素在未绝经乳腺癌患者与健康对照组之间差异无统计学意义( P>0.05)。有淋巴结转移的乳腺癌患者抵抗素、脂联素及瘦素水平与无淋巴结转移乳腺癌患者间差异有统计学意义( P<0.01)。逐步回归分析,脂联素及HDL-C的降低,瘦素和抵抗素的升高将会增加罹患乳腺癌的风险。血清脂联素降低和瘦素的增加与乳腺癌患者淋巴结的转移呈现相关性。

结论

血清脂联素水平的降低和抵抗素及瘦素水平的升高是患乳腺癌的危险因素。血清中较低的脂联素和较高的瘦素水平是乳腺癌转移的危险因素。

关键词: 脂联素; 抵抗素; 瘦素; 脂肪细胞因子; 乳腺癌
中图分类号:R446.1 文献标志码:A 文章编号:1673-8640(2011)01-0036-04
Serum levels of resistin, adiponectin and leptin in breast cancer patients and its clinical significance
FAN Jie1, LIU Bing2, CAO Wenyan3, GAO Weiguo1
1. Department of Clinical Laboratory, the Affiliated Hospital of Hebei University of Engineering, Hebei Handan 056029, China
2. Department of Surgery, Handan First Hospital, Hebei Handan 056029, China
3. Qinhuangdao Hospital of Traditional Chinese Medicine, Hebei Qinhuangdao 066000, China
Abstract
Objective

To investigate the change of serum levels of resistin, adiponectin and leptin in breast cancer patients and its clinical significance.

Methods

Blood samples were collected from 90 breast cancer patients (48 non-menopausal women and 42 menopausal women) and 50 healthy controls. Serum levels of resistin, adiponectin and leptin were determined. Fasting blood glucose(FBG) and blood lipids were assayed simultaneously.

Results

Serum levels of adiponectin and high-density lipoprotein cholesterol (HDL-C) were significantly decreased in the breast cancer patients in comparison to the controls ( P<0.01 and P<0.05 respectively). Serum levels of resistin( P<0.01), leptin( P<0.01), FBG ( P<0.01) and triglyceride(TG)in breast cancer patients were increased in contrast to the controls respectively. However, there was no significant difference of the serum levels of resistin, adiponectin and leptin between the non-menopausal breast cancer patients and the healthy controls ( P>0.05). The serum levels of resistin, adiponectin and leptin were significantly different between patients with and without lymph node metastasis ( P<0.01). Logistic regression analysis showed that the decreasing of adiponectin and HDL-C and the increasing of leptin and resistin would increase the risk for breast cancer. The decreasing of adiponectin and the increasing of leptin were associated with lymph node metastasis of breast cancer.

Conclusions

The decreased serum adiponectin levels and increased serum resistin and leptin levels are risk factors of breast cancer. The low serum adiponectin levels and high serum leptin levels are independent risk factors for the metastasis of breast cancer.

Keyword: Adiponectin; Resistin; Leptin; Adipocytokines; Breast cancer
引言

乳腺癌是一种严重危害女性身体健康的恶性肿瘤。脂肪组织作为一个内分泌器官, 分泌脂联素、抵抗素、瘦素及其他一些细胞因子[1]。这些脂肪组织细胞因子在肥胖女性乳腺癌的发病过程中起重要作用, 但其相关性仍需要进一步的研究。我们测定了乳腺癌患者血清中的脂联素、抵抗素、瘦素及与肥胖相关的代谢性因素, 旨在研究上述指标与乳腺癌患者发病、发展及转移之间的联系。

材料和方法
一、研究对象

选取2005年10月至2007年10月间河北工程大学附属医院90例被诊断为乳腺癌并经过手术治疗的患者作为病例组, 年龄3877岁, 其中48例为未绝经患者, 42例为绝经后患者。乳腺癌诊断均经病理证实, 其中浸润性导管癌49例, 浸润性小叶癌28例, 髓样癌及其他类型癌13例。乳腺癌的分期采用TNM临床分期, 90例患者中TNMⅠ 期15例, TNM Ⅱ 期48例, TNM Ⅲ 期27例。所有患者在手术前均未接受过放、化疗的治疗。选取50名经体检排除乳腺良恶性肿瘤及任何肿瘤病史及家族性肿瘤病史的健康妇女作为对照组, 年龄3563岁, 其中26名为未绝经者, 24名为绝经后者。

二、方法

1. 仪器

日立7170全自动生化分析仪, 美国Phoenix Biotech多功能酶标仪

2. 试剂和方法

空腹血糖(FBG)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、胆固醇(TC)测定均采用氧化酶法(试剂由上海科华东菱诊断用品有限公司生产)。抵抗素、脂联素及瘦素测定采用酶联免疫吸附试验(ELISA)(试剂由美国凤凰科技公司生产)。按照试剂说明书规定的程序检测。

3. 样本采集

空腹12 h, 采静脉血, 测定FBG、TG、HDL-C、LDL-C、TC。同时抽取3 mL静脉血后立即分离血清, 置-20 ℃冻存, 集中测定血清抵抗素、脂联素及瘦素水平。病例组的血样采集时间均在手术前。

三、统计学方法

统计数据采用SPSS13.0统计软件进行统计分析。计量数据用 ± s表示, 2组间比较应用t 检验, 多组间比较应用最小显著差(LSD) t检验, 血清抵抗素、脂联素、瘦素、血糖及血脂与乳腺癌发病和淋巴结转移危险性的关系应用Logistic多元逐步回归分析。

结果
一、病例组与对照组的血糖、血脂水平

病例组与对照组之间FBG、TG、HDL-C水平差异有统计学意义(P< 0.05、P< 0.01), 而TC在2组间差异无统计学意义(P> 0.05)。未绝经的2组之间血脂、血糖水平差异无统计学意义(P> 0.05); 绝经后2组之间HDL-C、FBG、TG水平差异有统计学意义(P< 0.05、P< 0.01)。淋巴结转移组与无淋巴结转移组之间HDL-C、FBG、TG以及TC水平差异有统计学意义(P< 0.05) ; TNMⅠ 期与Ⅲ 期组间FBG水平差异有统计学意义( P< 0.01), Ⅰ 期与Ⅱ 期、Ⅰ 期与Ⅲ 期组间TG水平差异有统计学意义( P< 0.05); 而Ⅱ 期与Ⅲ 期组间各指标比较差异均无统计学意义(P> 0.05)。见表1、表2。

表1 各组中抵抗素、脂联素、瘦素、血糖及血脂水平比较(± s)
二、病例组与对照组脂肪细胞因子水平

病例组血清脂联素水平明显低于对照组(P< 0.01); 病例组中绝经后的患者血清脂联素水平与对照组差异亦有统计学意义(P< 0.01); 但病例组中未绝经的患者血清脂联素水平与对照组差异无统计学意义(P> 0.05); 病例组血清瘦素及抵抗素水平均高于对照组(P< 0.01), 并且病例组绝经后的患者亦高于绝经后对照组(P< 0.01)。淋巴结转移组及无转移组血清抵抗素、脂联素及瘦素水平差异有统计学意义(P< 0.01); 根据TNM分期两两比较, Ⅰ 与Ⅱ 期、Ⅰ 期与Ⅲ 期患者间血清脂联素及瘦素水平差异有统计学意义(P< 0.01), 但抵抗素水平的差异无统计学意义(P> 0.05)。见表1、表2。

表2 病例组淋巴结转移及TNM分期各组抵抗素、脂联素、瘦素、血糖及血脂水平比较(± s)
三、血脂、血糖及脂肪细胞因子水平与乳腺癌发病风险及淋巴结转移的关系

多变量Logistic回归分析证明, 脂联素、HDL-C、瘦素及抵抗素是乳腺癌发病的危险性因素, 其比值比(OR)分别为:脂联素 0.805[95%可信区间(CI): 0.7040.921, P< 0.01); HDL-C 0.087(95%CI: 0.0110.691, P< 0.05); 瘦素 2.235 (95%CI: 1.8984.526, P< 0.01); 抵抗素 1.335 (95%CI: 1.1142.354, P< 0.05)。此外, 瘦素及脂联素是乳腺癌中淋巴结转移的危险性因素, 其OR值分别为:瘦素 0.724 (95%CI: 0.5040.921, P< 0.01), 脂联素 2.134 (95%CI: 1.7253.921, P< 0.01)。

讨论

本研究认为, 乳腺癌患者, 尤其是绝经后的乳腺癌患者血清中抵抗素显著增高, 可能增加乳腺癌患病风险, 并促进肿瘤细胞转移。Pamuk等[2]研究发现, 在淋巴瘤患者血清中抵抗素的含量显著升高, 认为抵抗素可能与某些肿瘤的产生相关。Di Simone等[3]发现, 抵抗素可以增强类滋养细胞的侵袭能力, 并可以诱导产生血管内皮生长因子(VEGF), 从而促进上皮细胞的管状增生。因此, 抵抗素可能与乳腺癌的发生及转移相关。但其具体作用机制仍需进一步研究。

本研究认为, 乳腺癌患者, 尤其是绝经后患者血清中脂联素含量显著降低, 与之前的一些研究一致[4]。病理学分级较高及病理学证实有淋巴结转移的乳腺癌患者血清中脂联素含量降低。因此, 低脂联素血症可能增加乳腺癌患病风险及淋巴结转移。脂联素受体R1及R2在正常乳腺上皮细胞及乳腺癌细胞中均有表达[5]。Dieudonne等[6]认为人乳腺癌MCF-7细胞表达脂联素受体, 与脂联素结合后会反馈抑制脂联素生成。因此, 脂联素通过其受体可直接抑制乳腺癌细胞增殖。脂联素还具有抗血管生成的作用[7], 生长因子可以通过脂联素抑制血管平滑肌细胞的增殖[8]。因此, 脂联素可以抑制新生血管形成从而抑制肿瘤的转移。

本研究中乳腺癌患者瘦素水平明显升高, 与文献[9, 10]报道一致。有学者认为瘦素会增加绝经后女性罹患乳腺癌的风险, 但与非绝经乳腺癌的发病无明显相关[11, 12]。也有学者认为血清中瘦素含量于绝经前后罹患乳腺癌风险并无不同[13]。Dieudonne等[14]发现人乳腺癌MCF-7细胞表达瘦素受体, 瘦素可影响人乳腺癌MCF-7细胞的生长。瘦素可以加速细胞增殖循环的速度, 从而促进乳腺癌细胞的增殖[15], 瘦素还可促进血管内皮细胞增殖, 促进血管增生[16]。因此, 瘦素可增强肿瘤侵袭性。本研究认为, 高TNM分期及有淋巴结转移的乳腺癌患者瘦素含量明显高于低TNM分期及无淋巴结转移的乳腺癌患者。乳腺癌组织中既有瘦素长型受体的表达, 也有短型受体表达[17]。正常乳腺细胞不表达瘦素受体(OB-R), 乳腺癌细胞OB-R阳性达83%; 正常乳腺细胞和乳腺癌细胞均有瘦素受体表达, 但超表达在癌细胞占92% , 正常乳腺细胞无此现象[18]。癌细胞扩散发生在OB-R阳性中占34%, 而OB-R阴性则未发生。国内亦有类似报道, 认为瘦素及其受体表达情况可作为乳腺癌诊断或预后的指标[19]。以上研究均提示瘦素及其受体在促进乳腺细胞生长和乳腺癌的发生中起重要作用。

本研究发现, FBG及血脂与乳腺癌的患病风险之间有紧密联系。乳腺癌患者的血糖较高。往往伴有高胰岛素血症, 胰岛素可以促进细胞的有丝分裂。胰岛素抵抗也许是肥胖与乳腺癌相关的其中一个作用机制。

总之, 血清中抵抗素、脂联素和瘦素的水平可能与乳腺癌的患病风险相关。

The authors have declared that no competing interests exist.

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