血清肿瘤分子标记物联合动态检测对肺癌诊疗的临床应用

doi:10.3877/cma.j.issn.1674-6902.2019.02.010

目的

探讨血清肿瘤分子标记物癌胚抗原(CEA)、鳞状上皮癌抗原(Scc-Ag)、胃泌素释放肽前体31-98(Pro-GRP31-98)联合动态监测在肺癌早期诊断和监控治疗中的临床应用价值。

方法

选取156例肺癌患者(肺癌组)、50例肺部良性病变患者(良性对照组)及50例健康体检者(正常对照组)为研究对象，采用电化学发光法及酶联免疫法检测三组人群血清CEA、Scc-Ag、Pro-GRP31-98水平，分析血清肿瘤分子标记物CEA、Scc-Ag、Pro-GRP31-98在肺癌早期诊断、临床分期、病理组织学分型、监控复发转移及判断预后的相关性。

结果

(1)肺癌组患者血清CEA、Scc-Ag、Pro-GRP31-98水平明显高于良性病变组及正常对照组，差异有统计学意义(P<0.01)。良性病变组与正常对照组血清CEA、Scc-Ag、Pro-GRP31-98水平比较无统计学差异(P>0.05)；(2)肺癌患者血清CEA、Scc-Ag、Pro-GRP31-98水平与性别、年龄、肿瘤发生部位无明显相关性(均P>0.05)；与肿瘤大小、临床分期、组织学类型、复发转移及治疗后明显相关，肺癌高分期(Ⅲ、Ⅳ期)组、转移组、复发组、治疗前与低分期(Ⅰ、Ⅱ期)组、无转移组、无复发组、治疗后血清CEA、Scc-Ag、Pro-GRP31-98水平相比较有明显增高(均P<0.01)；(3)CEA、Scc-Ag、Pro-GRP31-98分别在肺腺癌、鳞癌、小细胞癌血清阳性检出率较高，与其它两种病理组织学类型比较差异有统计学意义(P<0.01)；(4)CEA、Scc-Ag、Pro-GRP31-98诊断肺癌的敏感性分别为51.28%、48.72%、50.50%，特异性分别为96.00%、98.00%、94.00%，准确性分别为62.14%、60.68%、62.62%；两两组合CEA＋ Scc-Ag、CEA＋Pro-GRP31-98、Scc-Ag＋Pro-GRP31-98诊断肺癌的敏感性分别为61.54%、64.74%、62.18%，特异性分别为92.00%、90.00%、92.00%，准确性分别为69.27%、71.22%、69.76%；三项肿瘤分子标记物联合检测虽特异性有所降低(86.00%)，但敏感性、准确性明显提高，分别为96.46%、93.17%，与各单项及部分组合检测比较差异有统计学意义(均P<0.01)。

结论

肿瘤分子标记物CEA、Scc-Ag、Pro-GRP31-98与肺癌的发生发展密切相关，联合检测可以做到相互补充、相互印证，有利于早期诊断、临床早期干预；动态检测可以监控肿瘤复发、转移，指导治疗及评估预后。

关键词: 支气管肺癌, 肿瘤分子标记物，血清学, 联合检测, 临床应用

Objective

To study the clinical value of dynamic detection of serum tumor molecular markers, such as carcinoembryonic antigen tumor molecular markers (CEA), squamous cell carcinoma antigen (Scc Ag) and gastrin-releasing peptide precursor (Pro-GRP31-98), in the early diagnosis and treatment of lung cancer.

Methods

The serum levels of CEA, Scc Ag and Pro-GRP31-98 of 156 patients with lung cancer (lung cancer group), detected by electrochemical luminesence method (ECLIA) and enzyme-linked immunosorbent assay (ELISA), were compared with those of 50 patients with lung benign disease (lung benign group) and 50 people from health checkup (healthy control group) to analyze the clinical value of the three tumor markers in the diagnosis and treatment of lung cancer.

Results

①In the lung cancer group, the levels of CEA, Scc Ag and Pro-GRP31-98 were significantly higher than those of the lung benign group and the healthy control group (P<0.01). However, no significant difference was found between the lung benign group and the healthy control group (P>0.05). ②The levels of serum CEA, Scc Ag and Pro-GRP31-98 in the lung cancer group had no correlation with the gender, age or tumor location (P>0.05), but had close correlations with the tumor size, clinical stage, histological type, recurrence, transfer and treatment (P<0.01). The serum levels of CEA, Scc Ag and Pro-GRP31-98 in the lung cancer high differentiation group (Ⅲ and Ⅳ stages), transfer group, recurrence group, and pre-treatment group were significantly higher than those of the lung cancer low differentiation group (Ⅰ and Ⅱ stages), no metastasis group, no recurrence group, and post-treatment group (P<0.01). ③The serum CEA, Scc Ag and Pro-GRP31-98 had respectively higher positive detection rates of lung adenocarcinoma, squamous cell carcinoma and small cell carcinoma, and had a significant difference with the other two pathological types (P<0.01). ④The sensitivities of serum CEA, Scc Ag and Pro-GRP31-98 in the diagnosis of lung cancer were respectively 51.28%, 48.72% and 50.50%, the specificities were respectively 96.00%, 98.00% and 94.00%, and the accuracies were 62.14%, 60.68% and 62.62%, respectively. The sensitivities of CEA+ Scc-ag, CEA+ Pro-grp31-98, Scc-ag+ Pro-grp31-98 in the diagnosis of lung cancer were respectively 61.54%, 64.74% and 62.18%, the specificities were respectively 92.00%, 90.00% and 92.00%, and the accuracies were 69.27%, 71.22% and 69.76%, respectively. With the combined dynamic detection of the three serum tumor markers in the patients with lung cancer, the sensitivity and accuracy value reached 96.46% and 93.17%, respectively. It also had significant difference compared with single detection and pairwise combination detection (P<0.01).

Conclusion

Tumor markers CEA, scc-Ag and pro-grp31-98 are closely related to the occurrence and development of lung cancer. When they are combined with dynamic detection method, they can complement and reinforce each other, which is conducive to the early diagnosis and early clinical intervention. Dynamic detection can monitor the recurrence and metastasis of tumors, guiding the treatment and evaluating the prognosis.

Key words: Bronchogenic lung cancer, Tumor markers, serology, Combined detection, Clinical application

表1 三组血清肿瘤分子标记物水平比较(±s)

组　别	例数	CEA(ng/ml)	Scc-Ag(ng/ml)	Pro-GRP31-98(pg/ml)
肺癌组	156	53.26±19.37^a	33.64±15.79^a	115.36±62.34^a
良性对照组	50	1.89±0.96	0.97±0.23	15.84±3.69
正常对照组	50	1.87±0.89^b	0.95±0.22^b	15.23±3.12^b

表1 三组血清肿瘤分子标记物水平比较(±s)

组　别	例数	CEA(ng/ml)	Scc-Ag(ng/ml)	Pro-GRP31-98(pg/ml)
肺癌组	156	53.26±19.37^a	33.64±15.79^a	115.36±62.34^a
良性对照组	50	1.89±0.96	0.97±0.23	15.84±3.69
正常对照组	50	1.87±0.89^b	0.95±0.22^b	15.23±3.12^b

表2 肺癌患者不同临床病理因素血清肿瘤标记物水平比较(±s)

临床资料		例数	CEA(ng/ml)	Scc-Ag(ng/ml)	Pro-GRP31-98(pg/ml)
性别		?	?	?	?
?	男	89	54.69±20.06^a	32.26±13.67^a	117.82±63.28^a
?	女	67	52.80±18.76	52.80±16.25	112.71±60.37
年龄(岁)		?	?	?	?
?	≥50	92	53.96±19.67^a	34.27±15.87^a	113.29±61.27^a
?	<50	64	52.25±20.17	30.76±14.27	118.23±63.97
肿瘤部位		?	?	?	?
?	右肺	93	52.25±20.77^a	34.16±16.01^a	114.32±62.09^a
?	左肺	63	55.35±21.45	32.88±15.92	116.89±64.27
肿瘤直径		?	?	?	?
?	≥5 cm	106	62.43±25.14^b	40.12±17.24^b	137.24±69.36^b
?	<5 cm	50	33.82±12.76	27.16±10.17	69.42±32.41
病理组织学		?	?	?	?
?	腺癌	55	86.32±34.27^b	18.64±7.96	87.46±41.92
?	鳞癌	68	33.09±13.67	51.23±20.67^b	83.26±39.67
?	小细胞癌	33	39.41±15.27	23.67±9.25	228.24±92.37^b
临床分期		?	?	?	?
?	Ⅰ＋Ⅱ	67	29.27±10.64	18.73±6.32	57.38±22.37
?	Ⅲ＋Ⅳ	89	71.39±31.67^b	45.27±18.34^b	159.34±71.02^b
区域淋巴结转移		?	?	?	?
?	无	41	13.36±5.12	8.93±3.27	54.36±21.23
?	有	115	67.48±26.34^b	42.37±17.02^b	137.25±68.22^b
远处转移		?	?	?	?
?	无	133	44.33±17.69	23.61±8.64	79.23±32.37
?	有	23	104.49±46.12^b	90.31±32.89^b	326.34±116.34^b
复发		?	?	?	?
?	无	124	20.03±7.24	10.28±2.34	43.51±17.61
?	有	32	181.37±52.43^b	111.37±56.34^b	397.84±125.37^b
治疗		?	?	?	?
?	治疗前	156	53.26±19.37	33.64±15.79	115.36±62.34
?	治疗后	156	11.36±4.62^b	6.72±1.36^b	32.33±8.79^b

表2 肺癌患者不同临床病理因素血清肿瘤标记物水平比较(±s)

临床资料		例数	CEA(ng/ml)	Scc-Ag(ng/ml)	Pro-GRP31-98(pg/ml)
性别		?	?	?	?
?	男	89	54.69±20.06^a	32.26±13.67^a	117.82±63.28^a
?	女	67	52.80±18.76	52.80±16.25	112.71±60.37
年龄(岁)		?	?	?	?
?	≥50	92	53.96±19.67^a	34.27±15.87^a	113.29±61.27^a
?	<50	64	52.25±20.17	30.76±14.27	118.23±63.97
肿瘤部位		?	?	?	?
?	右肺	93	52.25±20.77^a	34.16±16.01^a	114.32±62.09^a
?	左肺	63	55.35±21.45	32.88±15.92	116.89±64.27
肿瘤直径		?	?	?	?
?	≥5 cm	106	62.43±25.14^b	40.12±17.24^b	137.24±69.36^b
?	<5 cm	50	33.82±12.76	27.16±10.17	69.42±32.41
病理组织学		?	?	?	?
?	腺癌	55	86.32±34.27^b	18.64±7.96	87.46±41.92
?	鳞癌	68	33.09±13.67	51.23±20.67^b	83.26±39.67
?	小细胞癌	33	39.41±15.27	23.67±9.25	228.24±92.37^b
临床分期		?	?	?	?
?	Ⅰ＋Ⅱ	67	29.27±10.64	18.73±6.32	57.38±22.37
?	Ⅲ＋Ⅳ	89	71.39±31.67^b	45.27±18.34^b	159.34±71.02^b
区域淋巴结转移		?	?	?	?
?	无	41	13.36±5.12	8.93±3.27	54.36±21.23
?	有	115	67.48±26.34^b	42.37±17.02^b	137.25±68.22^b
远处转移		?	?	?	?
?	无	133	44.33±17.69	23.61±8.64	79.23±32.37
?	有	23	104.49±46.12^b	90.31±32.89^b	326.34±116.34^b
复发		?	?	?	?
?	无	124	20.03±7.24	10.28±2.34	43.51±17.61
?	有	32	181.37±52.43^b	111.37±56.34^b	397.84±125.37^b
治疗		?	?	?	?
?	治疗前	156	53.26±19.37	33.64±15.79	115.36±62.34
?	治疗后	156	11.36±4.62^b	6.72±1.36^b	32.33±8.79^b

表3 血清CEA、Scc-Ag、Pro-GRP31-98在肺癌各组织学类型中阳性检出率比较 [n(%)]

检测项目	腺癌(n＝55)	鳞癌(n＝68)	小细胞癌(n＝33)
CEA	37(67.27)^a	18(26.47)	9(27.27)
Scc-Ag	14(25.45)	47(69.12)^a	6(18.18)
Pro-GRP31-98	15(27.27)	16(23.53)	25(75.76)^a

表3 血清CEA、Scc-Ag、Pro-GRP31-98在肺癌各组织学类型中阳性检出率比较 [n(%)]

检测项目	腺癌(n＝55)	鳞癌(n＝68)	小细胞癌(n＝33)
CEA	37(67.27)^a	18(26.47)	9(27.27)
Scc-Ag	14(25.45)	47(69.12)^a	6(18.18)
Pro-GRP31-98	15(27.27)	16(23.53)	25(75.76)^a

表4 血清CEA、Scc-Ag、Pro-GRP31-98单项及联合检测诊断肺癌的价值比较(%)

检测项目	敏感性	特异性	准确性	阳性预测值	阴性预测值
CEA	51.28	96.00	62.14	97.56	38.71
Scc-Ag	48.72	98.00	60.68	98.70	37.98
Pro-GRP31-98	50.50	94.00	62.62	96.47	38.84
CEA＋ Scc-Ag	61.54	92.00	69.27	96.00	43.40
CEA＋ Pro-GRP31-98	64.74	90.00	71.22	95.28	45.00
Scc-Ag＋ Pro-GRP31-98	62.18	92.00	69.76	96.04	43.81
CEA ＋ Scc-Ag＋Pro-GRP31-98	96.46^a	86.00	93.17^a	95.48	84.31^a

表4 血清CEA、Scc-Ag、Pro-GRP31-98单项及联合检测诊断肺癌的价值比较(%)

检测项目	敏感性	特异性	准确性	阳性预测值	阴性预测值
CEA	51.28	96.00	62.14	97.56	38.71
Scc-Ag	48.72	98.00	60.68	98.70	37.98
Pro-GRP31-98	50.50	94.00	62.62	96.47	38.84
CEA＋ Scc-Ag	61.54	92.00	69.27	96.00	43.40
CEA＋ Pro-GRP31-98	64.74	90.00	71.22	95.28	45.00
Scc-Ag＋ Pro-GRP31-98	62.18	92.00	69.76	96.04	43.81
CEA ＋ Scc-Ag＋Pro-GRP31-98	96.46^a	86.00	93.17^a	95.48	84.31^a

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Clinical value of dynamic detection of tumor molecular markers in serum in patients with lung cancer

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Clinical value of dynamic detection of tumor molecular markers in serum in patients with lung cancer