转录因子LMO3在弥漫性大B细胞淋巴瘤中的表达及对预后的临床意义

李丹; 雷鹏; 曹雨婷; 农卫霞

doi:10.7619/jcmp.20230785

转录因子LMO3在弥漫性大B细胞淋巴瘤中的表达及对预后的临床意义

石河子大学第一附属医院血液科, 新疆石河子, 832000

基金项目:

兵团财政科技计划项目 2021CA002

详细信息

通讯作者:
农卫霞, E-mail: 2557291951@qq.com

中图分类号: R551.2;R733
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出版历程
- 收稿日期: 2023-03-13
- 修回日期: 2023-05-23
- 网络出版日期: 2023-07-18

The expression of transcription factor LMO3 in diffuse large B-cell lymphoma and its prognostic significance

Department of Hematology, the First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, 832000

摘要

摘要:
目的
探讨转录因子LMO3在弥漫性大B细胞淋巴瘤(DLBCL)的表达及对预后的临床意义。
方法
收集82例石河子大学第一附属医院经病理检查确诊为DLBCL的患者的临床资料，采用免疫组织化学染色法检测LMO3在DLBCL中的表达，分析LMO3的表达与DLBCL临床特征及预后的关系。
结果
纳入的82例DLBCL患者中, LMO3阳性表达19例(23.2%), 阴性表达63例(76.8%)。LMO3表达患者在性别、国际预后指数(IPI)评分、乳酸脱氢酶(LDH)水平、免疫分型等方面差异均无统计学意义(P>0.05)。LMO3表达与年龄、临床分期(Ann Arbor分期)、B组症状、美国东部肿瘤协作组(ECOG)评分、CD5阳性有相关性(P < 0.05)。LMO3阳性组的无进展生存时间和总生存时间短于LMO3阴性组，无进展生存率和总生存率均低于LMO3阴性患者，差异有统计学意义(P < 0.05)。CD5、LMO3表达双阳性患者的无进展生存率和总生存率均低于双表达阴性患者，差异有统计学意义(P < 0.05)。单因素分析发现，年龄>60岁、CD5表达阳性、LMO3表达阳性、Ann Arbor分期为Ⅲ~Ⅳ、B组症状、ECOG评分>1分、IPI评分>2分是影响总生存时间的风险因素; 年龄>60岁、CD5表达阳性、LMO3表达阳性、Ann Arbor分期为Ⅲ~Ⅳ期、症状为B组症状、ECOG评分>1分、IPI评分>2分、治疗方案为CHOP是影响无进展生存时间的危险因素。多因素分析结果发现, B组症状和IPI评分>2分为影响总生存时间的独立危险因素。
结论
LMO3在DLBCL中的表达有可能成为预测患者预后的新型免疫位点。LMO3在DLBCL中的表达与其临床特征存在相关性, CD5与LMO3在DLBCL中的表达有明显相关性，有可能存在相互联系的致病机制或信号通路，有望成为新的免疫治疗靶点。
- LMO3 /
- 弥漫性大B细胞淋巴瘤 /
- 预后 /
- CD5 /
- 信号通路 /
- 致病机制 /
- 免疫位点 /
- 治疗靶点
Abstract:
Objective
To investigate the expression of transcription factor LMO3 in diffuse large B-cell lymphoma (DLBCL) and its prognostic significance.
Methods
The clinical data of 82 patients with DLBCL diagnosed by pathology in the First Affiliated Hospital of Shihezi University were collected. The expression of LMO3 in DLBCL was detected by immunohistochemical staining. The relationships of the expression of LMO3 with the clinical features and prognosis of DLBCL were analyzed.
Results
Among 82 patients with DLBCL, 19 (23.2%) were positive for LMO3 and 63 (76.8%) were negative. There were no significant differences in terms of gender, international prognostic index(IPI) score, lactate dehydrogenase (LDH) level, immunophenotype and etc. in LMO3 expression patients (P>0.05). The expression of LMO3 was correlated with age, Ann Arbor stage, symptoms in group B, Eastern Oncology Consortium (ECOG) score and positive expression for CD5(P < 0.05). The progression-free survival time and total survival time of LMO3 positive group were shorter than those of LMO3 negative group, the progression-free survival rate and overall survival rate of LMO3 positive patients were lower than those of LMO3 negative patients(P < 0.05). The progression-free survival rate and overall survival rate of CD5 and LMO3 double expression positive patients were lower than those of double expression negative patients (P < 0.05). Univariate analysis showed that age>60 years old, CD5 positive expression, LMO3 positive expression, Ⅲ to Ⅳ AnnArbor stage, group B symptoms, ECOG score>1, IPI score>2 were risk factors for overall survival, while age>60 years, CD5 positive expression, LMO3 positive expression, Ⅲ to Ⅳ AnnArbor stage, group B symptoms, ECOG score>1, IPI score>2, and CHOP regimen were risk factors for progression free survival. Multivariate analysis showed that group B symptoms and IPI score>2 were the independent risk factors of the total survival time.
Conclusion
The expression of LMO3 in DLBCL may become a new immune site to predict its prognosis. The expression of LMO3 in DLBCL is correlated with its clinical features, and there is a significant correlation between the expression of CD5 and LMO3 in DLBCL, and there may be a related pathogenic mechanism or signal pathway, which is expected to become a new target of immunotherapy.
- LMO3 /
- diffuse large B-cell lymphoma /
- prognosis /
- CD5 /
- signal pathway /
- pathogenic mechanism /
- immune sites /
- therapeutic target

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图 1 LMO3表达患者无进展生存率和总生存率预后生存曲线

A: LMO3表达患者的无进展生存率; B: LMO3表达患者的总生存率。

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图 2 CD5和LMO3表达患者的无进展生存率和总生存率预后生存曲线图

A: CD5、LMO3表达患者的无进展生存率; B: CD5、LMO3表达患者的总生存率。

下载: 全尺寸图片幻灯片

表 1 LMO3在不同患者中的表达[n(%)]

指标	分类	LMO3阳性(n=19)	LMO3阴性(n=63)	χ²	P
性别	男	15(78.9)	45(71.4)	0.4	0.517
	女	4(21.1)	18(28.6)
年龄	>60岁	8(42.1)	5(7.9)	10.3	0.001
	≤60岁	11(57.9)	58(92.1)
LDH水平	>正常值	8(42.1)	23(36.5)	0.2	0.659
	≤正常值	11(57.9)	40(63.5)
Ann Arbor分期	Ⅲ~Ⅳ期	9(47.4)	15(23.8)	3.1	0.048
	Ⅰ~Ⅱ期	10(52.6)	48(76.2)
症状	B组症状	7(36.8)	4(6.3)	9.2	0.002
	A组症状	12(63.2)	59(93.7)
ECOG评分	>1分	9(47.4)	7(11.1)	10.0	0.002
	≤1分	10(52.6)	56(88.9)
IPI评分	>2分	5(26.3)	6(9.5)	2.2	0.134
	≤2分	14(73.7)	57(90.5)
免疫学分型	GCB型	9(47.4)	43(68.3)	2.7	0.098
	非GCB型	10(52.6)	20(31.7)
MYC、BCL-2双阳性表达	是	3(15.8)	6(9.5)	0.1	0.728
	否	16(84.2)	57(90.5)
CD5	阳性	6(75.0)	2(25.0)	10.3	0.001
	阴性	13(17.6)	61(82.4)
治疗方案	CHOP	6(31.6)	23(36.5)	0.2	0.694
	RCHOP	13(68.4)	40(63.5)
LDH: 乳酸脱氢酶; ECOG: 美国东部肿瘤协作组; IPI: 国际预后指数。

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表 2 无进展生存时间的单因素和多因素分析

指标	单因素分析				多因素分析
指标	β	P	HR	95%CI	β	P	HR	95%CI
年龄	1.2	0.019	3.5	1.2~9.2	1.0	0.239	0.4	0.1~2.0
CD5阳性	2.8	< 0.001	16.9	6.0~47.8	1.0	0.438	2.8	0.2~36.3
LMO3阳性	1.9	< 0.001	6.5	2.4~17.8	0.7	0.349	2.0	0.5~8.7
LDH	0.9	0.086	2.4	0.9~6.4	—	—	—	—
Ann Arbor分期	1.3	0.013	3.5	1.4~9.5	0.5	0.557	0.6	0.1~2.9
B组症状	2.5	< 0.001	12.5	4.6~33.8	1.9	0.070	6.5	0.9~50.1
ECOG评分	1.8	< 0.001	6.3	2.3~16.8	0.6	0.363	1.9	0.5~7.8
IPI评分	1.6	0.002	5.1	1.9~14.2	0.9	0.158	2.6	0.7~9.4
免疫学分型	0.1	0.894	0.9	0.3~2.6	—	—	—	—
MYC、BCL-2表达双阳性	0.3	0.808	0.8	0.1~6.0	—	—	—	—
治疗方案	1.0	0.046	2.8	1.0~6.4	0.6	0.424	0.6	0.1~2.3

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表 3 总生存时间的单因素和多因素分析

指标	单因素分析				多因素分析
指标	β	P	HR	95%CI	β	P	HR	95%CI
年龄	1.7	0.007	5.6	1.6~19.4	< 0.1	0.981	1.0	0.2~8.2
CD5阳性	2.9	< 0.001	18.0	5.0~64.7	0.6	0.670	1.8	0.1~25.3
LMO3阳性	1.7	0.010	5.3	1.5~18.9	0.4	0.709	0.7	0.1~6.1
LDH水平	1.0	0.111	2.8	0.8~9.9	—	—	—	—
Ann Arbor分期	1.4	0.040	3.8	1.1~13.4	1.1	0.258	0.3	< 0.1~2.3
B组症状	3.0	< 0.001	19.2	4.9~74.5	3.1	0.005	21.4	2.5~185.4
ECOG评分	3.0	0.004	6.6	1.9~23.4	0.7	0.482	2.0	0.3~15.1
IPI评分	1.9	0.001	8.5	2.5~29.6	1.8	0.041	6.0	1.1~33.1
免疫学分型	0.2	0.747	1.2	0.3~4.8	—	—	—	—
MYC、BCL-2表达双阳性	-3.1	0.597	0.0	< 0.1~4 878.2	—	—	—	—
治疗方案	1.2	0.073	3.2	0.9~11.4	—	—	—	—

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表 4 LMO3表达患者的无进展生存时间和总生存时间比较月

指标	LMO3阳性	LMO3阴性
无进展生存时间	72.1(46.1, 96.2)	120.7(111.3, 130.1)
总生存时间	94.9(70.7, 119.2)	124.0(115.5, 132.6)

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