血清Hsp90α、eotaxin-2、TRAF6联合检测对早期结肠直肠癌的诊断及预测预后价值

doi:10.16150/j.1671-2870.2025.04.009

摘要/Abstract

摘要：

目的：分析早期结肠直肠癌患者血清热休克蛋白90α（heat shock protein 90α，Hsp90α）、噬酸性细胞趋化因子2（eosinophil chemotactic protein 2，eotaxin-2）、肿瘤坏死因子受体相关因子6（tumor necrosis factor receptor associated factor 6，TRAF6）表达情况及其临床诊断价值。方法：连续纳入2019年5月至2020年12月期间，本院收治的119例术后病理明确诊断的Ⅰ期和Ⅱ期结肠直肠癌患者为结肠直肠癌组，随访3年，并将生存患者分为复发转移组和未复发转移组；另选取121例结肠直肠腺瘤患者为良性病变组。采用酶联免疫吸附（enzyme-linked immunosorbent assay，ELISA）法检测血清Hsp90α、eotaxin-2、TRAF6含量，高于所有患者表达水平中位值则定义为高表达，反之为低表达。采用受试者工作特征（receiver operator characteristic，ROC）曲线分析血清Hsp90α、eotaxin-2、TRAF6鉴别诊断早期结肠直肠癌与良性病变的价值及预测结肠直肠癌患者复发转移的价值。曲线下面积（area under the curve，AUC）比较采用Z检验；采用Kaplan-Meier法分析指标与结肠直肠癌患者3年生存率的关系。结果：119例结肠直肠癌患者随访3年，92例生存（包括14例复发转移生存），27例复发转移死亡。结肠直肠癌组血清Hsp90α、eotaxin-2、TRAF6水平高于良性病变组（P<0.05）。肿瘤直径≥5 cm、TNM分期Ⅱ期的结肠直肠癌患者血清Hsp90α、eotaxin-2、TRAF6水平高于肿瘤直径<5 cm、TNM分期Ⅰ期患者（P<0.05）。血清Hsp90α、eotaxin-2、TRAF6单独和联合鉴别诊断早期结肠直肠癌与良性病变的AUC分别为0.783（95%CI为0.723~0.843）、0.795（95%CI为0.739~0.851）、0.753（95%CI为0.690~0.816）、0.906（95%CI为0.867~0.945），联合AUC高于各指标单独AUC（Z=3.411、3.151、4.054，P<0.05），灵敏度分别为52.99%、85.73%、73.12%、86.68%，特异度分别为75.98%、59.52%、71.12%、82.62%，Hsp90α、eotaxin-2、TRAF6的诊断临界值分别为178.27 ng/mL、198.77 pg/mL、3.49 μg/mL。结肠直肠癌血清Hsp90α、eotaxin-2、TRAF6高表达患者3年生存率分别为62.07%、61.67%、65.57%，低于低表达患者的91.80%、93.22%、89.66%（P<0.05）。复发转移组结肠直肠癌患者血清Hsp90α、eotaxin-2、TRAF6水平高于未复发转移组（P<0.05）。血清Hsp90α、eotaxin-2、TRAF6单独和联合预测结肠直肠癌复发转移的AUC分别为0.836（95%CI为0.760~0.911）、0.701（95%CI为0.597~0.804）、0.821（95%CI为0.741~0.900）、0.968（95%CI为0.934~0.998），联合AUC高于各指标单独AUC（Z=3.073、4.770、3.351，P<0.05）。结论：早期结肠直肠癌患者中血清Hsp90α、eotaxin-2、TRAF6水平升高，且与患者预后有关，三者联合有望成为临床辅助诊断、预测预后的标志物。

关键词: 早期结肠直肠癌, 热休克蛋白90α, 噬酸性细胞趋化因子2, 肿瘤坏死因子受体相关因子6, 诊断

Abstract:

Objective To analyze the expression and clinical diagnostic value of serum heat shock protein 90α (Hsp90α), eosinophil chemotactic protein 2 (eotaxin-2), and tumor necrosis factor receptor associated factor 6 (TRAF6) in patients with early colorectal cancer. Methods From May 2019 to December 2020, 119 patients with stage Ⅰ and stage Ⅱ colorectal cancer diagnosed by postoperative pathology admitted to our hospital were consecutively included in the colorectal cancer group. After a 3-year follow-up, surviving patients were divided into a recurrence and metastasis group and a non-recurrence and metastasis group.Additionally, 121 patients with colorectal adenoma were collected as the benign lesion group. Enzyme-linked immunosorbent assay (ELISA) method was used to detect serum levels of Hsp90α, eotaxin-2, and TRAF6. If the level was higher than the median expression level among all patients, it was defined as high expression; otherwise, it was defined as low expression. Receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of serum Hsp90α, eotaxin-2, and TRAF6 in distinguishing early colorectal cancer from benign lesions and in predic-ting recurrence and metastasis in colorectal cancer patients.Thearea under the curve (AUC) was comparedusing Z-test.Kaplan-Meier method was used to analyze the relationship between these indicators and 3-year survival rate of colorectal cancer patients. Results The serum levels of Hsp90α, eotaxin-2, and TRAF6 in the colorectal cancer group were higher than those in the benign lesion group (P<0.05). In colorectal cancer patients with a tumor diameter of ≥ 5 cm and TNM stage Ⅱ, the serum levels of Hsp90α, eotaxin-2, and TRAF6 were higher than in those with a tumor diameter of<5 cm and TNM stage Ⅰ (P<0.05). The AUC for differentiating early colorectal cancer from benign lesions using serum Hsp90α, eotaxin-2, and TRAF6 alone and in combination were 0.783 (95%CI: 0.723-0.843), 0.795 (95%CI: 0.739-0.851), 0.753 (95%CI: 0.690-0.816), and 0.906 (95%CI: 0.867-0.945), respectively. The combined AUC was higher than the individual AUC of each indicator (Z=3.411, 3.151, 4.054, P<0.05), with sensitivity values of 52.99%, 85.73%, 73.12%, and 86.68%, and specificity of 75.98%, 59.52%, 71.12%, and 82.62%, respectively.The diagnostic thresholdsfor Hsp90α, eotaxin-2, and TRAF6 were 178.27 ng/mL, 198.77 pg/mL, and 3.49 μg/mL, respectively. A total of 119 colorectal cancer patients were followed up for 3 years, with 92 surviving (including 14 survivors withrecurrence and metastasis) and 27 dying due to recurrence and metastasis. The 3-year survival rate of patients with high serum expression of Hsp90α, eotaxin-2, and TRAF6 were 62.07%, 61.67% and 65.57%, which were lower than that of patients with low expression, which were 91.80%, 93.22% and 89.66% (P<0.05). The serum levels of Hsp90α, eotaxin-2, and TRAF6 in colorectal cancer patients with recurrence and metastasis were higher than those in the non-recurrence and metastasis group (P<0.05). The AUC for predicting colorectal cancer recurrence and metastasis using serum Hsp90 α, eotaxin-2, and TRAF6 alone and in combination were 0.836 (95%CI: 0.760-0.911), 0.701 (95%CI: 0.597-0.804), 0.821 (95%CI: 0.741-0.900), and 0.968 (95%CI: 0.934-0.998), respectively. The combined AUC was higher than the individual AUC of each indicator alone (Z=3.073, 4.770, 3.351, P<0.05). Conclusion The serum levels of Hsp90α, eotaxin-2, and TRAF6 are higher in patients with early colorectal cancer, and they are associated with the patient’s prognosis. The combination of these three is expected to serve as clinical auxiliary diagnostic and prognostic markers.

Key words: Early colorectal cancer, Heat shock protein 90α, Eosinophil chemotactic protein 2, Tumor necrosis factor receptor associated factor 6, Diagnosis

中图分类号:

江南, 许亚聪, 刘佳瑶, 孙荣, 郑高歌, 徐菱遥, 闫春晓. 血清Hsp90α、eotaxin-2、TRAF6联合检测对早期结肠直肠癌的诊断及预测预后价值[J]. 诊断学理论与实践, 2025, 24(04): 423-430.

JIANG Nan, XU Yacong, LIU Jiayao, SUN Rong, ZHENG Gaoge, XU Lingyao, YAN Chunxiao. Diagnostic and prognostic value of combined detection of serum Hsp90α, eotaxin-2, and TRAF6 in early colorectal cancer[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(04): 423-430.

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Group	Cases	Hsp90α（ng/mL）	eotaxin-2（pg/mL）	TRAF6（μg/mL）
Benign lesion group	121	154.87±36.12	174.25±41.06	3.17±0.73
Colorectal cancer group	119	199.49±45.28	221.31±43.97	4.38±1.36
t		8.446	8.571	8.607
P		<0.001	<0.001	<0.001

Clinical and pathological features	Hsp90α（ng/mL）	t	P	eotaxin-2（pg/mL）	t	P	TRAF6（μg/mL）	t	P
Gender		0.544	0.587		1.964	0.052		0.234	0.815
Male	201.13±48.11			215.13±48.21			4.40±1.29
Female	196.25±42.08			233.52±48.32			4.34±1.38
Age（years）		1.179	0.241		1.495	0.138		0.202	0.840
<60	205.41±46.71			228.45±41.72			4.35±1.30
≥60	195.49±43.88			216.48±43.57			4.40±1.34
Tumor location		1.622	0.107		1.019	0.310		0.457	0.648
Colon	204.35±47.15			224.36±45.16			4.42±1.39
Rectum	190.24±40.83			215.51±44.78			4.30±1.30
Tumor diameter（cm）		5.478	<0.001		3.961	<0.001		3.889	<0.001
<5	184.09±45.17			210.43±43.12			4.05±1.30
≥5	231.08±41.22			243.62±42.47			5.06±1.39
TNM staging		9.389	<0.001		6.905	<0.001		4.956	<0.001
Stage Ⅰ	171.43±40.29			201.12±40.75			3.92±1.31
Stage Ⅱ	248.56±47.16			256.98±45.18			5.19±1.40

Group	Cases	Hsp90α （ng/mL）	eotaxin-2 （pg/mL）	TRAF6 （μg/mL）
Non recurrence and metastasis group	78	165.35±43.18	210.38±50.22	3.82±1.15
Recurrence and metastasis group	41	264.44±59.61	242.10±42.76	5.45±1.30
t		10.395	3.440	7.022
P		<0.001	0.001	<0.001