血清胱抑素C、尿酸水平与小细胞肺癌预后的相关性分析

摘要/Abstract

摘要：

目的探讨小细胞肺癌(SCLC)患者初治前血清胱抑素C与尿酸浓度对预后的影响。方法选取2015年4月至2018年12月在青岛大学附属医院诊断为SCLC的患者196例,收集患者治疗前血清胱抑素C与尿酸等血液学指标。通过受试者工作特征(ROC)曲线确定胱抑素C与尿酸的最佳临界值。用Kaplan-Meier方法进行生存分析。采用Cox比例风险模型进行单因素、多因素分析。结果患者治疗前血清胱抑素C与尿酸的最佳临界值分别为0.775 mg/L和296.45 μmol/L。生存分析显示,以最佳临界值为界,血清胱抑素C、尿酸浓度高的患者中位无进展生存时间(PFS)(5.49个月vs.8.57个月,χ²=35.943,P<0.001;6.67个月vs. 8.20个月,χ²=8.047,P=0.005)和总生存时间(OS)(13.37个月vs.23.95个月,χ²=21.355,P<0.001;14.13个月vs.20.97个月,χ²=11.333,P=0.001)均较浓度低的患者缩短。单因素分析显示,与PFS相关的因素有吸烟史(HR=0.707,95%CI为0.518~0.965,P=0.029)、分期(HR=1.776,95%CI为1.329~2.373,P<0.001)、一线化疗用药(HR=1.596,95%CI为1.072~2.376,P=0.021)、胸部放疗(HR=2.407,95%CI为1.803~3.214,P<0.001)、胱抑素C(HR=3.602,95%CI为1.716~7.561,P=0.001)、尿酸(HR=1.002,95%CI为1.000~1.003,P=0.036)及碱性磷酸酶(HR=1.010,95%CI为1.004~1.016,P=0.001);与OS相关的因素有吸烟史(HR=0.577,95%CI为0.382~0.870,P=0.009)、分期(HR=1.846,95%CI为1.295~2.630,P=0.001)、胸部放疗(HR=2.041,95%CI为1.426~2.921,P<0.001)、胱抑素C(HR=9.506,95%CI为3.278~27.564,P<0.001)及尿酸(HR=1.003,95%CI为1.001~1.005,P=0.006)。多因素分析显示,胸部放疗(HR=2.553,95%CI为1.774~3.672,P<0.001)、胱抑素C(HR=4.538,95%CI为1.875~10.982,P=0.001)及碱性磷酸酶(HR=1.011,95%CI为1.005~1.018,P=0.001)是PFS的独立预后因素;胱抑素C(HR=9.028,95%CI为2.680~30.413,P<0.001)是OS的独立预后因素。结论SCLC患者治疗前血清胱抑素C与尿酸浓度均与患者预后有一定关系,浓度升高者PFS和OS缩短,预后差。治疗前血清胱抑素C浓度高可能提示患者病情进展快、生存时间较短,需注意疾病的进展与复发。

关键词:小细胞肺癌,预后,胱抑素C,尿酸

Abstract:

ObjectiveTo explore the effects of serum cystatin C (Cys C) and uric acid (UA) concentrations before treatment on the prognosis of small cell lung cancer (SCLC) patients.MethodsA total of 196 patients diagnosed with SCLC in Affiliated Hospital of Qingdao University from April 2015 to December 2018 were selected, and hematological indicators such as serum Cys C and UA before treatment were collected. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values of Cys C and UA. The Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for univariate and multivariate analysis.ResultsThe optimal cut-off values of serum Cys C and UA before treatment were 0.775 mg/L and 296.45 μmol/L, respectively. Survival analysis showed that with the optimal cut-off value, the median progression-free survival (PFS) of patients with high concentrations of serum Cys C and UA (5.49 monthsvs. 8.57 months,χ²=35.943,P<0.001; 6.67 monthsvs. 8.20 months,χ²=8.047,P=0.005) and overall survival (OS) (13.37 monthsvs. 23.95 months,χ²=21.355,P<0.001; 14.13 monthsvs. 20.97 months,χ²=11.333,P=0.001) were shorter than those of patients with low concentrations. Univariate analysis showed that factors related to PFS were smoking history (HR=0.707, 95%CI: 0.518-0.965,P=0.029), staging (HR=1.776, 95%CI: 1.329-2.373,P<0.001), first-line medication (HR=1.596, 95%CI: 1.072-2.376,P=0.021), chest radiotherapy (HR=2.407, 95%CI: 1.803-3.214,P<0.001), Cys C (HR=3.602, 95%CI: 1.716-7.561,P=0.001), UA (HR=1.002, 95%CI: 1.000-1.003,P=0.036), and alkaline phosphatase (HR=1.010, 95%CI: 1.004-1.016,P=0.001); factors related to OS included smoking history (HR=0.577, 95%CI: 0.382-0.870,P=0.009), staging (HR=1.846, 95%CI: 1.295-2.630,P=0.001), chest radiotherapy (HR=2.041, 95%CI: 1.426-2.921,P<0.001), Cys C (HR=9.506, 95%CI: 3.278-27.564,P<0.001) and UA (HR=1.003, 95%CI: 1.001-1.005,P=0.006). Multivariate analysis showed that chest radiotherapy (HR=2.553, 95%CI: 1.774-3.672,P<0.001), Cys C (HR=4.538, 95%CI: 1.875-10.982,P=0.001) and alkaline phosphatase (HR=1.011, 95%CI: 1.005-1.018,P=0.001) were independent prognostic factors for PFS; Cys C (HR=9.028, 95%CI: 2.680-30.413,P<0.001) was an independent prognostic factor for OS.ConclusionBoth serum Cys C and UA concentrations before treatment in SCLC patients have a certain relationship with the prognosis of the patients. Those with elevated concentrations have shorter PFS and OS and poor prognosis. The high concentration of serum Cys C before treatment may indicate a rapid progression of the disease and a short survival time. It is necessary to pay attention to disease progression and recurrence.

Key words:Small cell lung carcinoma,Prognosis,Cystatin C,Uric acid

王浩澄, 董娅, 单东凤, 于壮. 血清胱抑素C、尿酸水平与小细胞肺癌预后的相关性分析[J]. 国际肿瘤学杂志, 2021, 48(1): 24-29.

Wang Haocheng, Dong Ya, Shan Dongfeng, Yu Zhuang. Correlation between serum cystatin C and uric acid levels and prognosis of small cell lung cancer[J]. Journal of International Oncology, 2021, 48(1): 24-29.

图/表7

表1

196例SCLC患者的临床资料"

临床病理特征	例(%)/中位数(范围)
性别
男	154(78.57)
女	42(21.43)
年龄(岁)
<60	83(42.35)
≥60	113(57.65)
吸烟史
有	139(70.92)
无	57(29.08)
ECOG评分
0	112(57.14)
1	84(42.86)
原发部位
右肺	119(60.71)
左肺	77(39.29)
分期
局限期	100(51.02)
广泛期	96(48.98)
一线化疗用药
依托泊苷联合铂类	166(84.69)
伊立替康联合铂类	30(15.31)
胸部放疗
有	102(52.04)
无	94(47.96)
胱抑素C(mg/L)^a	0.78(0.34~1.77)
尿酸(μmol/L)	285.00(77.30~579.00)
尿素氮(mmol/L)	5.07(1.53~11.77)
肌酐(μmol/L)	80.00(31.00~126.10)
碱性磷酸酶(U/L)	75.52(38.00~248.67)
腺苷脱氨酶(U/L)	10.00(2.00~26.00)
NLR	2.43(0.56~20.94)
PLR	158.74(55.21~521.19)

表1

图1

图2

图3

图4

表2

196例SCLC患者PFS及OS单因素分析"

因素	PFS				OS
因素	HR值	95%CI	P值		HR值	95%CI	P值
性别(男vs.女)	0.724	0.514~1.020	0.065	0.693		0.450~1.070	0.098
年龄(<60岁vs.≥60岁)	1.122	0.843~1.494	0.431	0.960		0.675~1.367	0.822
吸烟史(有vs.无)	0.707	0.518~0.965	0.029	0.577		0.382~0.870	0.009
ECOG评分(0vs.1)	1.075	0.809~1.429	0.618	1.072		0.752~1.529	0.700
原发部位(右肺vs.左肺)	1.118	0.839~1.491	0.446	0.774		0.537~1.115	0.169
分期(局限期vs.广泛期)	1.776	1.329~2.373	<0.001	1.846		1.295~2.630	0.001
因素	PFS				OS
因素	HR值	95%CI	P值		HR值	95%CI	P值
一线化疗用药(依托泊苷vs.伊立替康)	1.596	1.072~2.376	0.021	1.401		0.868~2.263	0.168
胸部放疗(有vs. 无)	2.407	1.803~3.214	<0.001	2.041		1.426~2.921	<0.001
胱抑素C	3.602	1.716~7.561	0.001	9.506		3.278~27.564	<0.001
尿酸	1.002	1.000~1.003	0.036	1.003		1.001~1.005	0.006
尿素氮	1.000	1.000~1.000	0.959	1.000		1.000~1.001	0.280
肌酐	1.000	0.991~1.010	0.927	1.007		0.994~1.019	0.280
碱性磷酸酶	1.010	1.004~1.016	0.001	1.003		0.997~1.009	0.346
腺苷脱氨酶	1.023	0.984~1063	0.248	1.028		0.983~1.075	0.227
NLR	1.002	0.955~1.052	0.922	1.022		0.964~1.084	0.458
PLR	1.000	0.999~1.001	0.409	1.000		0.999~1.002	0.715

表2

表3

196例SCLC患者PFS及OS多因素分析"

因素	PFS				OS
因素	HR值	95%CI	P值		HR值	95%CI	P值
吸烟史(有vs.无)	0.699	0.471~1.035	0.074	0.751		0.435~1.296	0.303
分期(局限期vs.广泛期)	1.106	0.756~1.619	0.604	1.418		0.884~2.275	0.147
一线化疗用药(依托泊苷vs.伊立替康)	0.969	0.602~1.559	0.897	—		—	—
胸部放疗(有vs.无)	2.553	1.774~3.672	<0.001	1.474		0.910~2.387	0.115
胱抑素C	4.538	1.875~10.982	0.001	9.028		2.680~30.413	<0.001
尿酸	0.998	0.996~1.000	0.116	0.999		0.966~1.001	0.286
碱性磷酸酶	1.011	1.005~1.018	0.001	—		—	—

表3

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