Association between monocyte-to-lymphocyte ratio and prognosis of patients with epithelial ovarian cancer

doi:10.3877/cma.j.issn.1673-5250.2017.05.006

Objective

To explore the association between monocyte-to-lymphocyte ratio (MLR) and prognosis of patients with epithelial ovarian cancer (EOC).

Methods

A total of 214 patients with EOC who underwent initial surgical resection between January 2005 to January 2015 in Second Clinical Medical College of North Sichuan Medical College were selected as research subjects. Clinical data of all subjects were collected by retrospective analysis. The receiver operating characteristic (ROC) curve of MLR predicting overall survival (OS) time in patients with EOC was drawn. The optimal cut-off value of MLR predicting OS time in patients with EOC was determined by ROC curve, and the EOC patients were categorized into two group according to the optimal cut-off value of MLR. The clinicopathological features and OS time of the 2 groups were compared statistically. Univariate and multivariate Cox regression analysis was used to analyze the factors that might affect OS time in patients with EOC.

Results

①According to the ROC curve of MLR predicting OS time in patients with EOC, the optimal cut-off value of MLR predicting OS time in patients with EOC was 0.26. Accordingly, all the 214 EOC patients were categorized into the high MLR group (n=128, MLR≥0.26) and low MLR group (n=86, MLR<0.26). There were no significant differences between two groups in the age, weight, body mass index (BMI) (P>0.05). ②The rates of patients with ≥62 years old, serous ovarian cancer histopathological type, Federation International of Gynecology and Obstetrics (FIGO) stage Ⅲ-Ⅳ, the fatality rate, and the serum carbohydrate antigen 125 (CA₁₂₅) level, white blood cell count, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in high MLR group all were higher those in low MLR group, and all the differences were statistically significant (P<0.05). There were no significant differences between 2 groups in the rates of satisfactory ovarian cancer cytoreductive surgery and combined with ascites, and hemoglobin level (P>0.05). ③The OS time of low MLR group was 87 months, which was obviously longer than that of high MLR group 38 months, and the difference was statistically significant (χ²=67.166, P<0.001). ④The multivariate Cox analysis results showed that FIGO stage Ⅲ-Ⅳ, serous ovarian cancer histopathological type, non-satisfactory ovarian cancer cytoreductive surgery, serum CA₁₂₅ level≥35 U/mL, MLR≥0.26, NLR and PLR all were independent risk factors of OS time in EOC patients (HR=8.370, 95%CI: 5.094-13.753, P<0.001; HR=1.851, 95%CI: 1.171-2.924, P=0.008; HR=0.345, 95%CI: 0.234-0.507, P<0.001; HR=2.434, 95%CI: 1.538-3.851, P<0.001; HR=3.364, 95%CI: 2.145-5.276, P<0.001; HR=1.106, 95%CI: 1.020-1.199, P=0.015; HR=0.998, 95%CI: 0.996-1.000, P=0.021).

Conclusions

MLR is an independent prognostic factor affecting the survival of patients with EOC. Since this study is a retrospective study and the sample size is relatively small, the authenticity and accuracy of MLR predicting the prognosis of EOC patients should be confirmed by multicenter, large sample and randomized controlled studies.

Key words: Epithelial ovarian cancer, Monocyte-to-lymphocyte ratio, Prognosis, Women

图1 单核细胞与淋巴细胞比值预测上皮性卵巢癌患者总体生存期的受试者工作特征曲线

表1 低MLR组与高MLR组上皮性卵巢癌患者的临床病理学特征比较

组别	例数	年龄[例数(%)]		组织病理学类型[例数(%)]		FIGO临床分期[例数(%)]		满意卵巢癌细胞减灭术[例数(%)]		血清CA₁₂₅水平[U/mL，M(P₂₅～P₇₅)]
组别	例数	≥62岁	<62岁	浆液性卵巢癌	其他类型	Ⅰ～Ⅱ期	Ⅲ～Ⅳ期	是	否	血清CA₁₂₅水平[U/mL，M(P₂₅～P₇₅)]
低MLR组	86	14(16.3)	72(83.7)	55(64.0)	31(36.0)	56(65.1)	30(34.9)	39(45.3)	47(54.7)	95.7(28.5～305.3)
高MLR组	128	34(26.6)	94(73.4)	91(71.1)	37(28.9)	43(33.6)	85(66.4)	57(44.5)	71(55.5)	284.3(107.6～2 889.7)
检验值	?	χ²＝5.304		χ²＝4.644		χ²＝19.312		χ²＝0.014		Z＝－5.063
P值	?	0.021		0.031		<0.001		0.906		<0.001
组别	例数	合并腹水[例数(%)]		随访结局[例数(%)]		血红蛋白水平(g/L，±s)	白细胞计数(×10⁹/L，±s)	NLR[M(P₂₅～P₇₅)]	PLR[M(P₂₅～P₇₅)]
组别	例数	是	否	病死率	存活率	血红蛋白水平(g/L，±s)	白细胞计数(×10⁹/L，±s)	NLR[M(P₂₅～P₇₅)]	PLR[M(P₂₅～P₇₅)]
低MLR组	86	31(36.0)	55(64.0)	30(34.9)	56(65.1)	113.2±18.4	7.0±2.1	2.4(1.8～3.2)	131.5(107.5～168.6)
高MLR组	128	47(36.7)	81(63.3)	109(85.2)	19(14.8)	113.9±21.0	7.9±2.4	4.2(2.6～6.3)	200.0(151.1～312.0)
检验值	?	χ²＝0.010		χ²＝57.109		t＝－0.279	t＝3.104	Z＝－6.012	Z＝－6.611
P值	?	0.920		<0.001		0.781	0.002	<0.001	<0.001

表1 低MLR组与高MLR组上皮性卵巢癌患者的临床病理学特征比较

组别	例数	年龄[例数(%)]		组织病理学类型[例数(%)]		FIGO临床分期[例数(%)]		满意卵巢癌细胞减灭术[例数(%)]		血清CA₁₂₅水平[U/mL，M(P₂₅～P₇₅)]
组别	例数	≥62岁	<62岁	浆液性卵巢癌	其他类型	Ⅰ～Ⅱ期	Ⅲ～Ⅳ期	是	否	血清CA₁₂₅水平[U/mL，M(P₂₅～P₇₅)]
低MLR组	86	14(16.3)	72(83.7)	55(64.0)	31(36.0)	56(65.1)	30(34.9)	39(45.3)	47(54.7)	95.7(28.5～305.3)
高MLR组	128	34(26.6)	94(73.4)	91(71.1)	37(28.9)	43(33.6)	85(66.4)	57(44.5)	71(55.5)	284.3(107.6～2 889.7)
检验值	?	χ²＝5.304		χ²＝4.644		χ²＝19.312		χ²＝0.014		Z＝－5.063
P值	?	0.021		0.031		<0.001		0.906		<0.001
组别	例数	合并腹水[例数(%)]		随访结局[例数(%)]		血红蛋白水平(g/L，±s)	白细胞计数(×10⁹/L，±s)	NLR[M(P₂₅～P₇₅)]	PLR[M(P₂₅～P₇₅)]
组别	例数	是	否	病死率	存活率	血红蛋白水平(g/L，±s)	白细胞计数(×10⁹/L，±s)	NLR[M(P₂₅～P₇₅)]	PLR[M(P₂₅～P₇₅)]
低MLR组	86	31(36.0)	55(64.0)	30(34.9)	56(65.1)	113.2±18.4	7.0±2.1	2.4(1.8～3.2)	131.5(107.5～168.6)
高MLR组	128	47(36.7)	81(63.3)	109(85.2)	19(14.8)	113.9±21.0	7.9±2.4	4.2(2.6～6.3)	200.0(151.1～312.0)
检验值	?	χ²＝0.010		χ²＝57.109		t＝－0.279	t＝3.104	Z＝－6.012	Z＝－6.611
P值	?	0.920		<0.001		0.781	0.002	<0.001	<0.001

图2 2组上皮性卵巢癌患者总体生存曲线比较

表2 上皮性卵巢癌患者总体生存期影响因素的Cox回归分析的变量含义及其赋值

自变量/因变量	变量名	赋值
OS期	y	表示患者接受卵巢癌细胞减灭术后第1天至死亡或本研究设定的随访截止时间
年龄	x₁	x₁＝0表示患者年龄<62岁，x₁＝1表示患者年龄≥62岁
FIGO临床分期	x₂	x₂＝0表示FIGO临床分期为Ⅰ～Ⅱ期，x₂＝1表示FIGO临床分期为 Ⅲ～Ⅳ期
组织病理学类型	x₃	x₃＝0表示除浆液性卵巢癌外的其他组织病理学类型，x₃＝1表示浆液性卵巢癌
是否为满意卵巢癌细胞减灭术	x₄	x₄＝0表示非满意卵巢癌细胞减灭术，x₄＝1表示满意卵巢癌细胞减灭术
是否合并腹水	x₅	x₅＝0表示未合并腹水，x₅＝1表示合并腹水
血清CA₁₂₅水平	x₆	x₆＝0表示血清CA₁₂₅水平<35 U/mL，x₆＝1表示血清CA₁₂₅水平≥35 U/mL
血红蛋白水平	x₇	x₇表示实际血红蛋白水平
白细胞计数	x₈	x₈＝0表示白细胞计数<8.16×10⁹/L，x₈＝1表示白细胞计数≥8.16×10⁹/L
MLR	x₉	x₉＝0表示MLR<0.26，x₉＝1表示MLR≥0.26
NLR	x₁₀	x₁₀表示实际NLR
PLR	x₁₁	x₁₁表示实际PLR

表2 上皮性卵巢癌患者总体生存期影响因素的Cox回归分析的变量含义及其赋值

自变量/因变量	变量名	赋值
OS期	y	表示患者接受卵巢癌细胞减灭术后第1天至死亡或本研究设定的随访截止时间
年龄	x₁	x₁＝0表示患者年龄<62岁，x₁＝1表示患者年龄≥62岁
FIGO临床分期	x₂	x₂＝0表示FIGO临床分期为Ⅰ～Ⅱ期，x₂＝1表示FIGO临床分期为 Ⅲ～Ⅳ期
组织病理学类型	x₃	x₃＝0表示除浆液性卵巢癌外的其他组织病理学类型，x₃＝1表示浆液性卵巢癌
是否为满意卵巢癌细胞减灭术	x₄	x₄＝0表示非满意卵巢癌细胞减灭术，x₄＝1表示满意卵巢癌细胞减灭术
是否合并腹水	x₅	x₅＝0表示未合并腹水，x₅＝1表示合并腹水
血清CA₁₂₅水平	x₆	x₆＝0表示血清CA₁₂₅水平<35 U/mL，x₆＝1表示血清CA₁₂₅水平≥35 U/mL
血红蛋白水平	x₇	x₇表示实际血红蛋白水平
白细胞计数	x₈	x₈＝0表示白细胞计数<8.16×10⁹/L，x₈＝1表示白细胞计数≥8.16×10⁹/L
MLR	x₉	x₉＝0表示MLR<0.26，x₉＝1表示MLR≥0.26
NLR	x₁₀	x₁₀表示实际NLR
PLR	x₁₁	x₁₁表示实际PLR

表3 上皮性卵巢癌患者总体生存期影响因素的单因素Cox回归分析结果

影响因素	B	SE	Wald值	P值	HR值	HR值95%CI
年龄	0.646	0.183	12.488	<0.001	1.907	1.333～2.729
FIGO临床分期	2.253	0.229	96.955	<0.001	9.520	6.079～14.909
组织病理学类型	0.685	0.192	12.692	<0.001	1.983	1.361～2.891
是否为满意卵巢癌细胞减灭术	－0.590	0.174	11.493	0.001	0.554	0.394～0.780
是否合并腹水	0.955	0.179	28.485	<0.001	2.599	1.830～3.691
血清CA₁₂₅水平	0.876	0.266	10.817	0.001	0.001	1.424～4.045
血红蛋白水平	－0.002	0.004	0.245	0.620	0.998	0.990～1.006
白细胞计数	0.081	0.032	6.375	0.012	1.084	1.018～1.154
MLR	1.623	0.221	54.037	<0.001	5.070	3.289～7.816
NLR	0.144	0.025	32.820	<0.001	1.155	1.099～1.213
PLR	0.002	0.001	21.606	<0.001	1.002	1.001～1.004

表3 上皮性卵巢癌患者总体生存期影响因素的单因素Cox回归分析结果

影响因素	B	SE	Wald值	P值	HR值	HR值95%CI
年龄	0.646	0.183	12.488	<0.001	1.907	1.333～2.729
FIGO临床分期	2.253	0.229	96.955	<0.001	9.520	6.079～14.909
组织病理学类型	0.685	0.192	12.692	<0.001	1.983	1.361～2.891
是否为满意卵巢癌细胞减灭术	－0.590	0.174	11.493	0.001	0.554	0.394～0.780
是否合并腹水	0.955	0.179	28.485	<0.001	2.599	1.830～3.691
血清CA₁₂₅水平	0.876	0.266	10.817	0.001	0.001	1.424～4.045
血红蛋白水平	－0.002	0.004	0.245	0.620	0.998	0.990～1.006
白细胞计数	0.081	0.032	6.375	0.012	1.084	1.018～1.154
MLR	1.623	0.221	54.037	<0.001	5.070	3.289～7.816
NLR	0.144	0.025	32.820	<0.001	1.155	1.099～1.213
PLR	0.002	0.001	21.606	<0.001	1.002	1.001～1.004

表4 上皮性卵巢癌患者总体生存期影响因素的多因素Cox回归分析结果

影响因素	B	SE	Wald值	P值	HR值	HR值95%CI
年龄	2.620	0.192	1.858	0.173	1.299	0.892～1.893
FIGO分期	2.125	0.253	70.305	<0.001	8.370	5.094～13.753
组织病理学类型	0.615	0.233	6.951	0.008	1.851	1.171～2.924
是否为满意卵巢癌细胞减灭术	－1.065	0.194	29.331	<0.001	0.345	0.234～0.507
是否合并腹水	0.357	0.184	3.774	0.052	1.429	0.997～2.049
血清CA₁₂₅水平	0.889	0.234	14.423	<0.001	2.434	1.538～3.851
MLR	1.213	0.230	27.912	<0.001	3.364	2.145～5.276
NLR	0.101	0.041	5.933	0.015	1.106	1.020～1.199
PLR	－0.002	0.001	5.294	0.021	0.998	0.996～1.000

表4 上皮性卵巢癌患者总体生存期影响因素的多因素Cox回归分析结果

影响因素	B	SE	Wald值	P值	HR值	HR值95%CI
年龄	2.620	0.192	1.858	0.173	1.299	0.892～1.893
FIGO分期	2.125	0.253	70.305	<0.001	8.370	5.094～13.753
组织病理学类型	0.615	0.233	6.951	0.008	1.851	1.171～2.924
是否为满意卵巢癌细胞减灭术	－1.065	0.194	29.331	<0.001	0.345	0.234～0.507
是否合并腹水	0.357	0.184	3.774	0.052	1.429	0.997～2.049
血清CA₁₂₅水平	0.889	0.234	14.423	<0.001	2.434	1.538～3.851
MLR	1.213	0.230	27.912	<0.001	3.364	2.145～5.276
NLR	0.101	0.041	5.933	0.015	1.106	1.020～1.199
PLR	－0.002	0.001	5.294	0.021	0.998	0.996～1.000

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