铜死亡相关基因<i>LIPT</i>1在子宫内膜癌中的表达及其临床意义

程翠; 郭苏阳; 张慧慧; 魏丽; 李艳; 王丽华; 江浩

doi:10.16766/j.cnki.issn.1674-4152.003790

铜死亡相关基因LIPT1在子宫内膜癌中的表达及其临床意义

doi: 10.16766/j.cnki.issn.1674-4152.003790

程翠¹,
郭苏阳¹,
张慧慧¹,
魏丽¹,
李艳¹,
王丽华¹,
江浩^2, ,

1.
蚌埠医科大学第一附属医院妇瘤科，安徽蚌埠 233004
2.
蚌埠医科大学第一附属医院放疗科

基金项目:

安徽省高校学校自然科学研究重点项目 2023AH052012

蚌埠医学院科学研究重点项目 2021byzd146

详细信息

通讯作者:
江浩，E-mail: jianghao1223@163.com

中图分类号: R737.33 R730.43
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出版历程
- 收稿日期: 2024-01-25
- 网络出版日期: 2025-01-20

Expression of cuprotosis-related gene LIPT1 in endometrial cancer and its clinical significance

1.
Department of Gynecologic Oncology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China

摘要

摘要: 目的脂酰转移酶1(LIPT1)是铜死亡关键基因之一，利用TCGA数据库和临床样本分析LIPT1在子宫内膜癌(UCEC) 中的表达及其临床意义。方法利用TCGA-UCEC样本和59例UCEC患者组织标本的免疫组化实验结果验证LIPT1 mRNA和蛋白的表达差异及其与临床特征关系，并进行预后分析。分析LIPT1与免疫细胞、免疫检查点的关系。结果结果显示，LIPT1基因在癌组织中的表达显著低于正常组织(P＜0.001)，在相应的邻近正常组织中高表达(P＜0.001)。免疫组化实验也显示LIPT1蛋白在癌组织[40.68%(24/59)]中的阳性表达率低于癌旁组织[76.92%(20/26), χ²=9.495，P=0.002]。不同LIPT1表达水平患者年龄(P=0.025)、病理分级(P=0.004)和病理类型(P＜0.001)差异均有统计学意义，临床样本分析显示，不同LIPT1表达水平患者年龄、病理分级差异均有统计学意义(P＜0.05)。LIPT1高表达的UCEC患者具有较差的总生存期(OS)、疾病特异性生存期(DSS)和无进展间期(PFI)，是OS的独立不良预后因素。LIPT1的表达与CD8⁺ T细胞、巨噬细胞、中性粒细胞相关(P＜0.05)。LIPT1的表达与PD-L1相关(P＜0.01)，与PD-1、CTLA-4无相关性。结论 LIPT1在UCEC中低表达，但其高水平与不良预后密切相关，可能与癌细胞免疫逃逸有关。有望成为UCEC新的治疗靶点。
- 子宫内膜癌 /
- 脂酰转移酶1 /
- 不良预后 /
- 治疗靶点
Abstract: Objective Lipoyltransferase 1 (LIPT1) is one of the key genes for copper death, and LIPT1 expression and its clinical significance were analysed in endometrial cancer (UCEC) using the TCGA database and clinical samples. Methods The immunohistochemical experimental results of TCGA-UCEC samples and tissue specimens of 59 UCEC patients were employed to substantiate the discrepancies in LIPT1 mRNA and protein expression and their correlation with clinical characteristics, as well as prognostic analyses. Subsequently, the relationship between LIPT1 and immune cells and immune checkpoints was subjected to analysis. Results The results showed that the expression of LIPT1 gene in cancer tissues was significantly lower than that in normal tissues (P < 0.001), and it was highly expressed in the adjacent normal tissues (P < 0.001). Immunohistochemical experiments also showed that the positive expression of LIPT1 protein was lower in cancerous tissues [40.68% (24/59)] than in paracancerous tissues [76.92% (20/26), χ²=9.495, P=0.002]. The differences in age (P=0.025), pathological grade (P=0.004) and pathological type (P < 0.001) of patients with different LIPT1 expression levels were statistically significant. The analysis of the clinical samples showed that the differences in age and pathological grading of patients with different LIPT1 expression levels were statistically significant (P < 0.05). Patients with UCEC who exhibited high LIPT1 expression exhibited poorer OS, DSS and PFI, which were identified as independent poor prognostic factors for OS. LIPT1 expression was found to be correlated with CD8⁺ T-cells, macrophages and neutrophils (P < 0.05). The expression of LIPT1 was correlated with PD-L1 (P < 0.01), but not correlated with PD-1 or CTLA-4. Conclusion LIPT1 is expressed at low levels in UCEC, but high levels are associated with poor prognosis and may be related to cancer cell immune escape. It is anticipated that this will become a new therapeutic target for UCEC.
- Uterine corpus endometrial carcinoma /
- Lipoyltransferase 1 /
- Poor prognosis /
- Therapeutic target

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图 1 LIPT1在不同组织中的表达及其诊断价值

注：A、B为LIPT1在UCEC中的表达情况；C为LIPT1诊断UCEC的ROC曲线。^aP < 0.001。

Figure 1. The expression of LIPT1 in different tissues and its diagnostic value

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图 2 LIPT1的表达与子宫内膜癌患者的预后关系

注：A为OS，B为DSS，C为PFI。

Figure 2. The relationship between LIPT1 expression and the prognosis of patients with UCEC

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表 1 TCGA数据库和临床样本的UCEC患者基线资料比较

Table 1. Comparision of baseline information in UCEC patients from the TCGA database and clinical samples

项目	TCGA样本[例(%)]		χ²值	P值	临床样本(例)		χ²值	P值
项目	LIPT1低表达	LIPT1高表达	χ²值	P值	阴性(n=35)	阳性(n=24)	χ²值	P值
年龄			5.405	0.025			4.684	0.030
≤60岁	116(21.1)	90(16.4)			17(28.8)	5(8.5)
＞60岁	158(28.8)	185(33.7)			18(30.5)	19(32.2)
BMI			1.395	0.238			0.332	0.565
≤30	100(19.3)	112(21.6)			14(23.7)	10(17.0)
＞30	161(31.0)	146(28.1)			21(35.6)	14(23.7)
临床分期			0.558	0.906			1.863	0.601
Ⅰ期	174(31.5)	168(30.4)			17(28.8)	13(22.0)
Ⅱ期	26(4.7)	25(4.5)			6(10.2)	4(6.8)
Ⅲ期	63(11.4)	67(12.1)			7(11.9)	6(10.2)
Ⅳ期	13(2.4)	16(2.9)			5(8.5)	1(1.6)
病理类型			16.785	＜0.001			0.128	0.721
子宫内膜样癌	226(40.9)	184(33.3)			29(49.1)	19(32.2)
混合性癌	9(1.6)	15(2.7)			0	0
浆液性癌	41(7.4)	77(13.9)			6(10.2)	5(8.5)
病理分级			11.037	0.004			8.957	0.011
G1	56(10.4)	42(7.8)			19(32.2)	5(8.5)
G2	72(13.3)	48(8.9)			10(17.0)	7(11.9)
G3	143(26.4)	180(33.3)			6(10.2)	12(20.2)
肿瘤残留			0.922	0.631
R0	200(48.4)	175(42.4)
R1	14(3.4)	8(1.9)
R2	9(2.2)	7(1.7)
肿瘤侵袭			0.025	0.875
＜50%	138(29.1)	121(25.5)
≥50%	113(23.8)	102(21.5)
更年期状态			2.377	0.305
绝经前期	22(4.3)	13(2.6)
围绝经期	8(1.6)	9(1.8)
绝经后期	225(44.5)	229(45.3)

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表 2 Cox回归分析中各变量赋值情况

Table 2. Assignment of variables for Cox regression analysis

变量	赋值方法
年龄	≤60岁=0，＞60岁=1
BMI	≤30=0，＞30=1
临床分期	Ⅰ~Ⅱ期=0，Ⅲ~Ⅳ期=1
病理类型	子宫内膜样癌=0，混合型或浆液型癌=1
病理分级	G1=0，G2和G3=1
肿瘤残留	R0=0，R1和R2=1
肿瘤侵袭	≤50%=0，＞50%=1
更年期状态	绝经前期=0，围绝经期或绝经后期=1
LIPT1	低表达=0，高表达=1

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表 3 子宫内膜癌患者OS的Cox回归分析

Table 3. Cox regression analysis of OS in patients with UCEC

变量	单因素Cox回归分析			多因素Cox回归分析
变量	HR值	95% CI	P值	HR值	95% CI	P值
年龄	1.847	1.160~2.940	0.010	1.858	1.266~2.725	0.002
BMI	0.967	0.636~1.470	0.876
临床分期	3.543	2.355~5.329	＜0.001	4.843	2.540~9.237	＜0.001
病理类型	2.628	1.746~3.957	＜0.001	0.836	0.439~1.593	0.586
病理分级	11.604	2.855~47.167	＜0.001	8.652	1.170~63.951	＜0.001
肿瘤残留	3.101	1.768~5.440	＜0.001	2.062	1.044~4.074	0.037
肿瘤侵袭	2.813	1.744~4.535	＜0.001	1.275	0.701~2.320	0.425
更年期状态	0.828	0.382~1.794	0.632
LIPT1	1.587	1.053~2.392	0.027	2.254	1.252~4.059	0.007

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