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中华妇幼临床医学杂志(电子版) ›› 2020, Vol. 16 ›› Issue (01) : 100 -106. doi: 10.3877/cma.j.issn.1673-5250.2020.01.013

所属专题： 文献；

论著

淋巴细胞与单核细胞比值对早期宫颈癌患者盆腔淋巴结转移的预测价值
唐英1, 唐方祥1, 胡辉权1,†(), 徐凡1, 宾冬梅2   
  1. 1. 川北医学院附属南充市中心医院妇科，四川　637000
    2. 南充市妇幼保健院，四川　637000
  • 收稿日期:2019-10-18 修回日期:2020-01-07 出版日期:2020-02-01
  • 通信作者: 胡辉权

Predictive value of preoperative lymphocyte-to-monocyte ratio on pelvic lymph node metastasis of early cervical cancer patients

Ying Tang1, Fangxiang Tang1, Huiquan Hu1,†(), Fan Xu1, Dongmei Bin2   

  1. 1. Department of Gynecology, Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
    2. Nanchong Maternal and Child Care Service Centre, Nanchong 637000, Sichuan Province, China
  • Received:2019-10-18 Revised:2020-01-07 Published:2020-02-01
  • Corresponding author: Huiquan Hu
  • About author:
    Corresponding author: Hu Huiquan, Email:
  • Supported by:
    Science & Technology Program by Science & Technology Department of Sichuan Province(2015JY0056); Program by Bureau of Science & Technology and Intellectual Property of Nanchong City, Sichuan Province(17YFZJ0005, 18YFZJ0012)
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引用本文：

唐英, 唐方祥, 胡辉权, 徐凡, 宾冬梅. 淋巴细胞与单核细胞比值对早期宫颈癌患者盆腔淋巴结转移的预测价值[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(01): 100-106.

Ying Tang, Fangxiang Tang, Huiquan Hu, Fan Xu, Dongmei Bin. Predictive value of preoperative lymphocyte-to-monocyte ratio on pelvic lymph node metastasis of early cervical cancer patients[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2020, 16(01): 100-106.

目的

探讨淋巴细胞与单核细胞比值(LMR)对早期宫颈癌患者盆腔淋巴结转移(PLNM)的预测价值。

方法

选择2008年1月至2018年1月，于川北医学院附属南充市中心医院初次接受宫颈癌根治性术的516例早期宫颈癌患者为研究对象。根据是否发生PLNM，将其分为PLNM(＋)组(n＝113)和PLNM(－)组(n＝403)。采用回顾性分析法，分析所有受试者的临床病例资料。采用χ2检验，对2组患者年龄、国际妇产科联盟(FIGO)临床分期，手术切除组织的病理学分级、组织病理学类型、肿瘤直径、血清鳞状细胞癌抗原(SCC-Ag)含量，术中是否发现脉管癌栓、宫旁浸润，宫颈间质浸润深度，以及LMR构成比等进行统计学比较。绘制LMR预测宫颈癌PLNM的受试者工作特征(ROC)曲线，对LMR预测早期宫颈癌患者发生PLNM进行分析，并计算ROC曲线下面积(ROC-AUC)。采用多因素非条件logistic回归分析，判断LMR预测早期宫颈癌患者发生PLNM的准确性。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。2组患者年龄比较，差异无统计学意义(P>0.05)。

结果

①单因素分析结果：PLNM(＋)组与PLNM(－)组患者FIGO临床分期、手术切除组织的病理学分级、组织病理学类型、肿瘤直径、血清SCC-Ag含量、术中是否发现脉管癌栓及宫旁浸润、宫颈间质浸润深度、LMR构成比比较，差异均有统计学意义(χ2＝13.057、18.998、9.584、85.667、7.225、88.538、69.807、32.644、126.453，P<0.05)。②多因素非条件logistic回归分析结果：早期宫颈癌患者FIGO临床分期为ⅡA期(OR＝2.805，95%CI：1.224～4.160，P＝0.009)，手术切除组织的病理学分级为G1(OR＝2.256，95%CI：1.245～6.323，P＝0.013)，脉管癌栓(OR＝5.818，95%CI：3.139～10.782，P<0.001)，宫旁浸润(OR＝4.482，95%CI：1.730～11.615，P<0.002)，肿瘤直径≥4 cm(OR＝3.955，95%CI：2.119～7.383，P<0.001)，以及血清SCC-Ag含量≥1.6 ng/mL(OR＝1.909，95%CI：1.057～3.446，P＝0.032)，均为早期宫颈癌患者发生PLNM的危险因素，而LMR>2.2(OR＝0.155，95%CI：0.081～0.296，P<0.001)，则为早期宫颈癌患者发生PLNM的保护因素。③ROC曲线分析结果：LMR预测早期宫颈癌患者PLNM的ROC-AUC为0.790(95%CI：0.753～0.825，P<0.001)。根据约登指数(Youden index)最大原则，LMR预测早期宫颈癌患者发生PLNM的最佳临界值为2.2，此时其预测早期宫颈癌患者发生PLNM的敏感度为66.4%，特异度为85.9%。

结论

术前外周血LMR>2.2，可作为预测早期宫颈癌发生PLNM的保护因素。

关键词: 宫颈肿瘤, 肿瘤，鳞状细胞, 淋巴细胞与单核细胞比值, 淋巴转移, 淋巴细胞，肿瘤浸润, ROC曲线, 妇女
Objective

To explore the value of lymphocyte-to-monocyte ratio (LMR) on pelvic lymph node metastasis (PLNM) of early cervical cancer patients.

Methods

The clinical and pathological data of 516 patients with early cervical cancer whose initial treatment were radical hysterectomy in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from January 2008 to January 2018 were selected into this study. According to being accompanied with PLNM or not, they were divided into PLNM (+ ) group (n=113) and PLNM(-)group (n=403). Retrospective analysis was used to analyze clinical data of all subjects. Chi-square was used to statistically compare the proportions of the age, International Federation of Gynecology and Obstetrics (FIGO) clinical stages, histopathological grades, histopathological types, vessel carcinoma embolus, parametrial invasion, cervical interstitial invasion depth, tumor diameters, levels of serum squamous cell carcinoma antigen(SCC-Ag), LMR between two groups. The receiver operating characteristic (ROC) curve of LMR predicting PLNM in early cervical cancer patients was drawn and analyzed, and the area under ROC curve (ROC-AUC) was calculated. The accuracy of LMR in the prediction of PLNM in early cervical cancer patients was evaluated by multivariate unconditional logistic regression analysis. This study met the requirements of the World Medical Association Declaration of Helsinki revised in 2013. There was no significant difference between two groups in age (P>0.05).

Results

①The results of univariate analysis showed that there were significant differences in proportions of FIGO clinical stages, histopathological grades, histopathological types, tumor diameters, levels of serum SCC-Ag, vessel carcinoma embolus, parametrial invasion, depth of cervical interstitial invasion and LMR (χ2=13.057, 18.998, 9.584, 85.667, 7.225, 88.538, 69.807, 32.644, 126.453; P<0.05). ②The results of multivariate unconditional logistic regression analysis showed that FIGO clinical stage ⅡA (OR=2.805, 95%CI: 1.224-4.160, P=0.009), histopathological grade G1 (OR=2.256, 95%CI: 1.245-6.323, P=0.013), vessel carcinoma embolus (OR=5.818, 95%CI: 3.139-10.782, P<0.001), parametrial invasion (OR=4.482, 95%CI: 1.730-11.615, P<0.002), tumor diameters≥4 cm (OR=3.955, 95%CI: 2.119-7.383, P<0.001), levels of serum SCC-Ag≥1.6 ng/mL (OR=1.909, 95%CI: 1.057-3.446, P=0.032) were risk factors of PLNM in early cervical cancer patients, while LMR > 2.2 (OR=0.155, 95%CI: 0.081-0.296, P<0.001) was the protective factor of PLNM in early cervical cancer patients. ③The ROC curve of LMR predicting PLNM of early cervical cancer showed that the ROC-AUC was 0.790 (95%CI: 0.753-0.825, P<0.001). According to the maximum principle of the Youden index, the optimal cut-off value of LMR predicting PLNM in patients with early cervical cancer was 2.2, and the sensitivity and specificity were 66.4% and 85.9%, respectively.

Conclusion

Peripheral blood LMR>2.2 is an independent protective factor to predict PLNM of early cervical cancer.

Key words: Uterine cervical neoplasms, Neoplasms, squamous cell, Lymphocyte-to-monocyte ratio, Lymphatic metastasis, Lymphocytes, tumor-infiltrating, ROC curve, Women
表1 本组516例早期宫颈癌患者的一般临床资料
项目 结果 项目 结果
年龄[岁，M(P25～P75)] 49(28～72) 宫旁浸润[例数(%)] ?
BMI[kg/m2，M(P25～P75)] 23.7(16.5～32.0) ? 阳性 45(8.7)
FIGO临床分期[例数(%)] ? ? 阴性 471(91.3)
? ⅠB期 402(77.9) 脉管癌栓[例数(%)] ?
? ⅡA期 114(22.1) ? 阳性 471(91.3)
组织病理学类型[例数(%)] ? ? ? 阴性
? 鳞癌 406(78.7) 宫颈间质浸润深度[例数(%)] ?
? 腺癌 103(20.0) ? >2/3 180(34.9)
? 腺鳞癌 6(1.1) ? ≤2/3 336(65.1)
? 其他类型 1(0.2) 腹膜后淋巴结转移[例数(%)] ?
组织病理学分级[例数(%)] ? ? 阳性 403(78.1)
? G1 56(10.8) ? 阴性 113(21.9)
? G2 390(75.6) 肿瘤直径[cm，M(P25～P75)] 2.5(0.1～11.0)
? G3 70(13.6) 血清SCC-Ag含量[ng/mL，M(P25～P75)] 1.6(0.6～54.5)
单核细胞计数[×109/L，M(P25～P75)] 0.6(0.1～4.8) 淋巴细胞计数[×109/L，M(P25～P75)] 1.8(0.3～7.1)
表2 2组早期宫颈癌患者发生盆腔淋巴结转移影响因素的单因素分析结果[例数(%)]
组别 例数 年龄 FIGO临床分期 手术切除组织病理学分级
<49岁 ≥49岁 ⅠB期 ⅡA期 G1 G2/G3
PLNM(＋)组 113 51(45.1) 62(54.9) 63(55.8) 50(44.2) 25(22.1) 88(77.9)
PLNM(－)组 403 190(47.1) 213(52.9) 296(73.4) 107(26.6) 31(7.7) 372(92.3)
χ2值 ? 0.144 13.057 18.998
P值 ? 0.705 <0.001 <0.001
组别 例数 组织病理学类型 脉管癌栓 宫旁浸润
鳞癌 非鳞癌 阳性 阴性 阳性 阴性
PLNM(＋)组 113 77(68.1) 36(31.9) 81(71.7) 32(28.3) 32(28.3) 81(71.7)
PLNM(－)组 403 329(81.6) 74(18.4) 97(24.0) 306(76.0) 13(3.2) 390(96.8)
χ2值 ? 9.584 88.538 69.807
P值 ? 0.002 <0.001 <0.001
组别 例数 宫颈间质浸润深度 肿瘤直径 血清SCC-Ag含量
≥2/3 <2/3 >4 cm ≤4 cm ≥1.6 ng/mL <1.6 ng/mL
PLNM(＋)组 113 65(57.5) 48(42.5) 58(51.3) 55(48.7) 70(61.9) 43(38.1)
PLNM(－)组 403 115(28.5) 288(71.5) 47(11.7) 356(88.3) 192(47.6) 211(52.4)
χ2值 ? 32.644 85.667 7.225
P值 ? <0.001 <0.001 0.007
组别 例数 LMR
≤2.2 >2.2
PLNM(＋)组 113 75(66.4) 38(33.6)
PLNM(－)组 403 57(14.1) 346(85.9)
χ2值 ? 126.453
P值 ? <0.001
表3 早期宫颈癌患者发生盆腔淋巴结转移影响因素的多因素非条件logistic回归分析变量含义及赋值
自变量/因变量 变量名 赋值
PLNM y y＝0表示早期宫颈癌患者PLNM(－)；y＝1表示早期宫颈癌患者PLNM(＋)
FIGO临床分期 x1 x1＝0表示FIGO临床分期为ⅠB期；x1＝1表示FIGO临床分期为ⅡA期
组织病理学分级 x2 x2＝0表示手术切除组织病理学分级为G2和G3；x2＝1表示手术切除组织病理学分级为G1
组织病理学类型 x3 x3＝0表示除鳞癌外的其他组织病理学类型；x3＝1表示鳞癌
脉管癌栓 x4 x4＝0表示未合并脉管癌栓；x4＝1表示合并脉管癌栓
宫旁浸润 x5 x5＝0表示未合并宫旁浸润；x5＝1表示合并宫旁浸润
宫颈间质浸润深度 x6 x6＝0表示宫颈间质浸润深度<2/3；x6＝1表示宫颈间质浸润深度≥2/3
肿瘤直径 x7 x7＝0表示肿瘤直径≤4 cm；x7＝1表示肿瘤直径>4 cm
血清SCC-Ag含量 x8 x8＝0表示血清SCC-Ag含量<1.6 ng/mL；x8＝1表示血清SCC-Ag含量≥1.6 ng/mL
LMR x9 x9＝0表示LMR≤2.2；x9＝1表示LMR>2.2
表4 早期宫颈癌患者发生盆腔淋巴结转移影响因素的多因素非条件logistic回归分析结果
影响因素 B SE Wald值 P值 OR值 OR值95%CI
常数项 －2.549 0.485 27.664 <0.001 0.078 —
FIGO临床分期 0.814 0.312 6.800 0.009 2.256 1.224～4.160
组织病理学分级 1.032 0.415 6.190 0.013 2.805 1.245～6.323
组织病理学类型 0.365 0.354 1.063 0.303 1.440 0.720～2.882
脉管癌栓 1.761 0.315 31.299 <0.001 5.818 3.139～10.782
宫旁浸润 1.500 0.486 9.537 0.002 4.482 1.730～11.615
宫颈间质浸润深度 －0.056 0.320 0.031 0.861 0.945 0.505～1.770
肿瘤直径 1.375 0.319 18.636 <0.001 3.955 2.119～7.383
血清SCC-Ag含量 0.064 0.301 4.600 0.032 1.909 1.057～3.446
LMR －1.864 0.330 31.887 <0.001 0.155 0.081～0.296
图1 LMR预测早期宫颈癌患者发生PLNM的ROC曲线
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