血清Hsp90α联合β2-MG检测在结直肠癌早期诊断和预后评估中的应用价值

doi:10.11958/20251176

摘要/Abstract

摘要：

目的探究血清热休克蛋白90α（Hsp90α）联合β2-微球蛋白（β2-MG）检测在结直肠癌（CRC）早期诊断和预后评估中的应用价值。方法选取101例首次治疗的CRC患者为CRC组，同期本院收治的100例结肠良性肿瘤患者为良性肿瘤组，在本院健康体检者94例为对照组。酶联免疫吸附试验（ELISA）检测所有受试者血清Hsp90α、β2-MG水平；术后2年内每3个月随访1次，第3年每6个月随访1次，共随访3年，统计CRC患者3年内生存状况。受试者工作特证（ROC）曲线分析血清Hsp90α、β2-MG对CRC的诊断价值；Kaplan-Meier法绘制Hsp90α、β2-MG不同表达水平CRC患者的生存曲线并进行比较。结果对照组、良性肿瘤组、CRC组血清Hsp90α、β2-MG水平逐次升高（P<0.05）。不同性别、年龄、病灶位置CRC患者血清Hsp90α、β2-MG水平差异无统计学意义，肿瘤直径>5 cm、低分化程度、TNM分期Ⅲ期及淋巴结转移患者血清Hsp90α、β2-MG水平分别高于肿瘤直径≤5 cm、中高分化程度、TNM分期Ⅰ—Ⅱ期及淋巴结未转移患者（P<0.05）。ROC曲线结果显示，血清Hsp90α、β2-MG联合诊断的效能优于单独诊断（P<0.05）。以CRC患者血清Hsp90α、β2-MG表达水平平均值76.66 μg/L、6.52 μg/L为界，将患者分为Hsp90α高表达组（59例）、Hsp90α低表达组（42例）和β2-MG高表达组（63例）、β2-MG低表达组（38例）。101例CRC患者死亡31例，生存70例，总生存率为69.31%。Kaplan-Meier生存曲线显示，Hsp90α和β2-MG高表达组3年生存率均低于Hsp90α和β2-MG低表达组（均P<0.01）。结论血清Hsp90α、β2-MG在CRC患者中表达水平均升高，且二者与CRC的发生、发展及预后密切相关。

关键词: 结直肠肿瘤, HSP90热休克蛋白质类, β2微球蛋白, 预后, 早期诊断

Abstract:

Objective To explore the application value of serum heat shock protein 90α (Hsp90α) combined with β2-microglobulin (β2-MG) detection in the early diagnosis and prognosis of colorectal cancer (CRC). Methods A total of 101 patients with CRC who received their first treatment were selected as the CRC group (no surgery, radiotherapy or chemotherapy before enrollment), 100 patients with benign colon tumor admitted to our hospital during the same period were selected as the benign tumor group and 94 healthy individuals who underwent physical examinations in our hospital were used as the control group. The levels of serum Hsp90α and β2-MG in all subjects were detected by ELISA. Follow-up was conducted every three months within the first two years after surgery, and every six months in the third year, for a total follow-up period of 3 years, and the survival status of CRC patients within 3 years was recorded. ROC curve analysis was used to evaluate the diagnostic value of serum Hsp90α and β2-MG for CRC. The Kaplan-Meier method was used to draw the survival curves of CRC patients with different expression levels of Hsp90α and β2-MG. Results The serum levels of Hsp90α and β2-MG increased successively in the control group, the benign tumor group and the CRC group (P<0.05). There were no significant differences in serum levels of Hsp90α and β2-MG between CRC patients of different genders, ages and lesion locations. The levels of serum Hsp90α and β2-MG in patients with tumor diameter > 5 cm, low differentiation degree, TNM stage Ⅲ and lymph node metastasis were higher than those in patients with tumor diameter ≤ 5 cm, moderate to high differentiation degree, TNM stage Ⅰ-Ⅱ and no lymph node metastasis (P<0.05). The ROC results showed that the combined diagnostic efficacy of serum Hsp90α and β2-MG was superior to that of serum Hsp90α or β2-MG alone (Z = 2.433, 2.435, P<0.05). Based on the average expression levels of serum Hsp90α and β2-MG in CRC patients (76.66 μg/L and 6.52 μg/L), patients were divided into the high expression group of Hsp90α (59 cases), the low expression group of Hsp90α (42 cases), the high expression group of β2-MG (63 cases) and the low expression group of β2-MG (38 cases). Among the 101 CRC patients, 31 died and 70 survived, with a total survival rate of 69.31%. The Kaplan-Meier survival curve showed that the 3-year survival rates of patients with high expression levels of Hsp90α and β2-MG were lower than theose of patients with low expression levels of Hsp90α and β2-MG (P<0.01). Conclusion The expression levels of serum Hsp90α and β2-MG are both elevated in CRC patients, and they are closely related to the occurrence, development and prognosis of CRC.

Key words: colorectal neoplasms, HSP90 heat-shock proteins, beta 2-microglobulin, prognosis, early diagnosis

中图分类号:

R735.3

图/表 6

参考文献 19

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组别	n	Hsp90α/（μg/L）	β2-MG/（μg/L）
对照组	94	48.33±8.71	2.11±0.46
良性肿瘤组	100	63.59±9.84^a	4.37±1.58^a
CRC组	101	76.66±10.37^ab	6.52±1.63^ab
F		208.375^＊＊	259.617^＊＊

组别	n	Hsp90α/（μg/L）	β2-MG/（μg/L）
对照组	94	48.33±8.71	2.11±0.46
良性肿瘤组	100	63.59±9.84^a	4.37±1.58^a
CRC组	101	76.66±10.37^ab	6.52±1.63^ab
F		208.375^＊＊	259.617^＊＊

临床特征	n	Hsp90α	t	β2-MG	t
性别
男	59	77.06±10.56	0.454	6.72±1.70	1.492
女	42	76.11±10.11	0.454	6.23±1.53	1.492
年龄
≤55岁	46	76.08±10.03	0.516	6.30±1.51	1.256
>55岁	55	77.15±10.66	0.516	6.71±1.73	1.256
病灶位置
直肠	49	76.28±10.15	0.358	6.25±1.47	1.651
结肠	52	77.02±10.58	0.358	6.78±1.78	1.651
肿瘤大小
≤5 cm	57	74.77±9.87	2.085^＊	6.13±1.37	2.697^＊＊
>5 cm	44	79.10±10.90	2.085^＊	7.02±1.97	2.697^＊＊
分化程度
中/高	62	74.64±9.79	2.462^＊	6.08±1.38	3.341^＊＊
低	39	79.86±11.28	2.462^＊	7.21±2.01	3.341^＊＊
TNM分期
Ⅰ—Ⅱ期	58	74.01±9.79	2.975^＊＊	5.89±1.46	4.424^＊＊
Ⅲ期	43	80.23±11.15	2.975^＊＊	7.36±1.87	4.424^＊＊
淋巴结转移
否	60	74.23±10.24	2.850^＊＊	6.12±1.41	2.972^＊＊
是	41	80.22±10.56	2.850^＊＊	7.11±1.94	2.972^＊＊

临床特征	n	Hsp90α	t	β2-MG	t
性别
男	59	77.06±10.56	0.454	6.72±1.70	1.492
女	42	76.11±10.11	0.454	6.23±1.53	1.492
年龄
≤55岁	46	76.08±10.03	0.516	6.30±1.51	1.256
>55岁	55	77.15±10.66	0.516	6.71±1.73	1.256
病灶位置
直肠	49	76.28±10.15	0.358	6.25±1.47	1.651
结肠	52	77.02±10.58	0.358	6.78±1.78	1.651
肿瘤大小
≤5 cm	57	74.77±9.87	2.085^＊	6.13±1.37	2.697^＊＊
>5 cm	44	79.10±10.90	2.085^＊	7.02±1.97	2.697^＊＊
分化程度
中/高	62	74.64±9.79	2.462^＊	6.08±1.38	3.341^＊＊
低	39	79.86±11.28	2.462^＊	7.21±2.01	3.341^＊＊
TNM分期
Ⅰ—Ⅱ期	58	74.01±9.79	2.975^＊＊	5.89±1.46	4.424^＊＊
Ⅲ期	43	80.23±11.15	2.975^＊＊	7.36±1.87	4.424^＊＊
淋巴结转移
否	60	74.23±10.24	2.850^＊＊	6.12±1.41	2.972^＊＊
是	41	80.22±10.56	2.850^＊＊	7.11±1.94	2.972^＊＊

指标	截断值/ ( μg/L)	AUC	95%CI	敏感度/ %	特异度/ %	约登指数
Hsp90α	72.27	0.851	0.797~0.905	81.2	69.3	0.532
β2-MG	5.87	0.853	0.800~0.906	81.2	68.0	0.492
两者联合	-	0.932	0.897~0.966	80.2	73.5	0.537