非小细胞肺癌患者血清HMGB2和HMGB3水平及临床意义

摘要/Abstract

摘要：

目的探究非小细胞肺癌（NSCLC）患者的血清高迁移率族蛋白（HMGB）2和HMGB3水平及临床意义。方法选取2020年1月—2022年1月西安医学院第一附属医院收治的137例NSCLC患者作为NSCLC组，另选取同期健康体检者90例作为健康组，比较两组血清HMGB2、HMGB3水平，分析血清HMGB2、HMGB3水平与NSCLC患者临床病理特征的关系；根据NSCLC患者预后情况分为预后良好组（n=86）和预后不良组（n=51），并比较两组的临床资料；采用多因素logistic回归分析NSCLC患者预后的影响因素；采用受试者操作特征（ROC）曲线分析血清HMGB2、HMGB3对NSCLC患者预后的预测价值。结果NSCLC组的血清HMGB2[（6.35±1.66）ng/ml比（2.58±0.76）ng/ml，t=20.19，P<0.001]、HMGB3[（2.48±0.56）ng/ml比（1.09±0.13）ng/ml，t=23.13，P<0.001]水平均高于健康组。有吸烟史（t=2.80，P=0.006；t=5.04，P<0.001）、有淋巴结转移（t=3.53，P=0.001；t=4.02，P<0.001）、TNM分期为Ⅲ~Ⅳ期（t=2.58，P=0.011；t=3.82，P<0.001）的NSCLC患者血清HMGB2、HMGB3水平均显著高于无吸烟史、无淋巴结转移、TNM分期为Ⅰ~Ⅱ期的患者。预后不良组患者的血清HMGB2[（7.80±1.83）ng/ml比（5.49±1.56）ng/ml，t=7.85，P<0.001]、HMGB3[（2.91±0.78）ng/ml比（2.23±0.43）ng/ml，t=6.58，P<0.001）]水平均高于预后良好组，有淋巴结转移（χ²=4.81，P=0.028）、有吸烟史（χ²=11.67，P=0.001）、TNM分期的Ⅲ~Ⅳ期（χ²=6.18，P=0.013）患者占比均显著高于预后良好组。多因素logistic回归分析结果显示，淋巴结转移（OR=1.96，95%CI为1.14~3.36，P=0.015）、吸烟史（OR=2.02，95%CI为1.33~3.06，P=0.001）、TNM分期（OR=2.28，95%CI为1.35~3.86，P=0.002）、HMGB2（OR=2.01，95%CI为1.40~2.91，P<0.001）、HMGB3（OR=1.99，95%CI为1.25~3.15，P=0.003）水平均为NSCLC患者预后的独立影响因素。ROC曲线分析显示，血清HMGB2、HMGB3单独和联合预测NSCLC患者预后情况的曲线下面积（AUC）分别为0.833、0.862、0.922，二者联合预测的AUC显著高于血清HMGB2（Z=2.44，P=0.015）、HMGB3（Z=2.54，P=0.011）单独预测。结论NSCLC患者血清HMGB2、HMGB3水平上调，且与不良预后密切相关，二者联合检测对NSCLC患者预后具有一定的预测效能。

关键词:癌,非小细胞肺,HMGB2蛋白质,HMGB3蛋白质

Abstract:

ObjectiveTo investigate the levels of serum high mobility group box （HMGB） 2 and HMGB3 and clinical significance in patients with non-small cell lung cancer （NSCLC）.MethodsA total of 137 NSCLC patients admitted to the First Affiliated Hospital of Xi'an Medical University from January 2020 to January 2022 were selected as the NSCLC group， and another 90 cases who underwent healthy medical checkups during the same period were selected as the healthy group. Serum HMGB2 and HMGB3 levels were compared between the two groups. The relationship between serum HMGB2 and HMGB3 levels and the clinical and pathological characteristics of NSCLC patients was analyzed. NSCLC patients were divided into a good prognosis group （n=86） and a poor prognosis group （n=51） according to the prognosis， and the clinical data of the two groups were compared. Multivariate logistic regression was used to analyze the influencing factors of the prognosis of NSCLC patients. Receiver operator characteristic （ROC） curve was used to analyze the predictive value of serum HMGB2 and HMGB3 on the prognosis of NSCLC patients.ResultsSerum HMGB2 [（6.35±1.66） ng/mlvs.（2.58±0.76） ng/ml，t=20.19，P<0.001] and HMGB3 [（2.48±0.56） ng/mlvs.（1.09±0.13） ng/ml，t=23.13，P<0.001] levels in NSCLC group were higher than those in healthy group. Serum HMGB2 and HMGB3 levels of NSCLC patients with a history of smoking （t=2.80，P=0.006；t=5.04，P<0.001）， lymph node metastasis （t=3.53，P=0.001；t=4.02，P<0.001）， and TNM stage Ⅲ-Ⅳ （t=2.58，P=0.011；t=3.82，P<0.001） were significantly higher than those of patients with no history of smoking， no lymph node metastasis， and TNM stage Ⅰ-Ⅱ. The serum levels of HMGB2 [（7.80±1.83） ng/mlvs.（5.49±1.56） ng/ml，t=7.85，P<0.001] and HMGB3 [（2.91±0.78） ng/mlvs.（2.23±0.43） ng/ml，t=6.58，P<0.001）] in the poor prognosis group were higher than those in the good prognosis group， and the proportion of patients with lymph node metastasis （χ²=4.81，P=0.028）， history of smoking （χ²=11.67，P=0.001）， and TNM stage Ⅲ-Ⅳ （χ²=6.18，P=0.013） was significantly higher than that in the good prognosis group. Multivariate logistic regression analysis showed that lymph node metastasis （OR=1.96， 95%CI： 1.14-3.36，P=0.015）， smoking history （OR=2.02， 95%CI： 1.33-3.06，P=0.001）， TNM stage （OR=2.28， 95%CI： 1.35-3.86，P=0.002）， HMGB2 （OR=2.01， 95%CI： 1.40-2.91，P<0.001）， and HMGB3 （OR=1.99， 95%CI： 1.25-3.15，P=0.003） levels were independent influencing factors of prognosis of NSCLC patients. ROC curve analysis showed that the area under the curve （AUC） of serum HMGB2 and HMGB3 alone and in combination to predict the prognosis of NSCLC patients were 0.833， 0.862 and 0.922， respectively， and the AUC predicted by the combination was significantly higher than that predicted by serum HMGB2 （Z=2.44，P=0.015） and HMGB3 （Z=2.54，P=0.011） alone.ConclusionSerum HMGB2 and HMGB3 levels are up-regulated in NSCLC patients and are closely associated with poor prognosis， and the combined detection of the two has certain predictive efficacy for prognosis of NSCLC patients.

Key words:Carcinoma,non-small-cell lung,HMGB2 protein,HMGB3 protein

刘昊, 靳二梅, 丁红娟, 金磊. 非小细胞肺癌患者血清HMGB2和HMGB3水平及临床意义[J]. 国际肿瘤学杂志, 2024, 51(7): 448-452.

Liu Hao, Jin Ermei, Ding Hongjuan, Jin Lei. Levels of serum HMGB2 and HMGB3 and clinical significance in non-small cell lung cancer patients[J]. Journal of International Oncology, 2024, 51(7): 448-452.

图/表6

组别	HMGB2	HMGB3
健康组（n=90）	2.58±0.76	1.09±0.13
NSCLC组（n=137）	6.35±1.66	2.48±0.56
t值	20.19	23.13
P值	<0.001	<0.001

表1

表2

血清HMGB2、HMGB3水平与NSCLC患者临床病理特征的关系（ng/ml，$\bar{x}\pm s$）"

临床病理特征	例数	HMGB2	t/F值	P值	HMGB3	t/F值	P值
年龄（岁）
<50	69	6.17±1.23	1.23	0.222	2.40±0.39	1.60	0.111
≥50	68	6.53±2.10	1.23	0.222	2.56±0.73	1.60	0.111
性别
男	76	6.43±2.06	0.61	0.544	2.53±0.64	1.13	0.261
女	61	6.25±1.16	0.61	0.544	2.42±0.46	1.13	0.261
吸烟史
有	82	6.68±1.87	2.80	0.006	2.68±0.55	5.04	<0.001
无	55	5.86±1.35	2.80	0.006	2.19±0.57	5.04	<0.001
TNM分期
Ⅰ~Ⅱ	59	5.93±1.56	2.58	0.011	2.26±0.33	3.82	<0.001
Ⅲ~Ⅳ	78	6.67±1.74	2.58	0.011	2.65±0.73	3.82	<0.001
病理类型
腺癌	88	6.21±2.02	1.20	0.232	2.41±0.55	1.90	0.059
鳞状细胞癌	49	6.58±1.01	1.20	0.232	2.60±0.58	1.90	0.059
淋巴结转移
有	72	6.83±1.86	3.53	0.001	2.67±0.42	4.02	<0.001
无	65	5.82±1.44	3.53	0.001	2.27±0.72	4.02	<0.001
分化程度
高分化	33	6.52±1.58			2.61±0.63
中分化	56	6.31±1.42	0.33	0.718	2.52±0.41	2.20	0.114
低分化	48	6.28±1.20			2.35±0.69

表2

表3

不同预后的NSCLC患者临床病理特征比较[例（%）/ $\bar{x}\pm s$]"

临床病理特征	预后良好组（n=86）	预后不良组（n=51）	χ²/t值	P值
性别
男	51（59.30）	25（49.02）	1.37	0.242
女	35（40.70）	26（50.98）	1.37	0.242
年龄（岁）	52.45±12.83	53.16±10.66	0.33	0.740
吸烟史
有	42（48.84）	40（78.43）	11.67	0.001
无	44（51.16）	11（21.57）	11.67	0.001
淋巴结转移
有	39（45.35）	33（64.71）	4.81	0.028
无	47（54.65）	18（35.29）	4.81	0.028
病理类型
腺癌	51（59.30）	37（72.55）	2.45	0.118
鳞状细胞癌	35（40.70）	14（27.45）	2.45	0.118
TNM分期
Ⅰ~Ⅱ	44（51.16）	15（29.41）	6.18	0.013
Ⅲ~Ⅳ	42（48.84）	36（70.59）	6.18	0.013
分化程度
高分化	17（19.77）	16（31.37）	2.48	0.290
中分化	38（44.18）	18（35.29）
低分化	31（36.05）	17（33.34）
HMGB2（ng/ml）	5.49±1.56	7.80±1.83	7.85	<0.001
HMGB3（ng/ml）	2.23±0.43	2.91±0.78	6.58	<0.001

表3

变量	β值	SE值	Waldχ²值	OR值	95%CI	P值
淋巴结转移	0.670	0.276	5.90	1.96	1.14~3.36	0.015
吸烟史	0.701	0.213	10.83	2.02	1.33~3.06	0.001
TNM分期	0.825	0.268	9.49	2.28	1.35~3.86	0.002
HMGB2	0.700	0.187	14.02	2.01	1.40~2.91	<0.001
HMGB3	0.687	0.235	8.54	1.99	1.25~3.15	0.003

表4

指标	截断值（ng/ml）	特异性（%）	敏感性（%）	AUC	95%CI	约登指数
HMGB2	6.97	86.05	64.71	0.833^a	0.759~0.891	0.508
HMGB3	2.64	90.70	78.43	0.862^b	0.793~0.915	0.691
二者联合		83.72	88.24	0.922	0.863~0.961	0.720

表5

图1

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