Significance of transcription factor LMO3 in evaluating prognosis of patients with endometrial carcinoma

Jiali LIU; Beibei XUAN; Quan QUAN; Sainan GONG; Xiaoling MU

doi:10.16016/j.2097-0927.202110101

您当前的位置：

首页 >

文章列表页 >

Significance of transcription factor LMO3 in evaluating prognosis of patients with endometrial carcinoma

Clinical Medicine | 更新时间：2026-01-09

- Significance of transcription factor LMO3 in evaluating prognosis of patients with endometrial carcinoma
- Journal of Army Medical University Vol. 44, Issue 10, Pages: 1054-1060(2022)
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院妇科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202110101
  CLC： R341;R730.7;R737.33
- Received：18 October 2021，
  
  Revised：2022-01-06，
  
  Published：30 May 2022
- 稿件说明：
移动端阅览
Jiali LIU, Beibei XUAN, Quan QUAN, et al. Significance of transcription factor LMO3 in evaluating prognosis of patients with endometrial carcinoma[J]. Journal of Army Medical University, 2022, 44(10): 1054-1060.
DOI：

Jiali LIU, Beibei XUAN, Quan QUAN, et al. Significance of transcription factor LMO3 in evaluating prognosis of patients with endometrial carcinoma[J]. Journal of Army Medical University, 2022, 44(10): 1054-1060. DOI： 10.16016/j.2097-0927.202110101.

摘要

目的

探讨转录因子LMO3表达水平对子宫内膜癌患者预后的影响。

方法

应用TCGA、GeneMANIA、STRING数据库分析子宫内膜癌组织中LMO3表达与患者预后的关系，以及LMO3的基因互作关系、LMO3与TP53突变的关系。收集51例2011年3月至2014年12月在重庆医科大学附属第一医院接受手术且组织病理学诊断为子宫内膜癌患者的子宫内膜组织石蜡切片及临床信息，并进行免疫组织化学染色，分析LMO3在子宫内膜癌组织中的表达及其与子宫内膜癌患者临床病理特征的关系。利用SPSS绘制生存曲线及COX多因素进行回归分析。在子宫内膜癌细胞中过表达LMO3后验证其对肿瘤细胞迁移的影响。

结果

TCGA数据库分析结果显示，在子宫内膜癌患者中LMO3高表达组的总生存期和无病生存期均显著低于LMO3低表达组(

＜0.05)，LMO3在TP53突变型患者中的表达水平显著高于TP53野生型患者，通过GeneMANIA及STRING数据库分析发现与LMO3相互作用的基因主要有NHLH2、LDB2等。免疫组织化学染色结果显示LMO3高表达组患者的无病生存期低于LMO3低表达组(

=0.005)，多因素COX分析提示LMO3可作为子宫内膜癌的预后因素。过表达LMO3后，子宫内膜癌细胞的迁移能力增强。

结论

LMO3高表达的子宫内膜癌患者预后差，其可能与LMO3过表达促进子宫内膜癌细胞的迁移有关。

Abstract

Objective

To investigate the significance of transcription factor LIM domain only 3 (LMO3) expression level in the prognosis of patients with endometrial carcinoma (EC).

Methods

The Cancer Genome Atlas (TCGA)

GeneMANIA and STRING databases were used to analyze the relationship between LMO3 expression in EC tissues and the prognosis of patients

as well as the genes interacting with LMO3

and the correlation of LMO3 with TP53 mutation. The paraffin sections and clinical information of 51 patients with EC who underwent surgery in our hospital from March 2011 to December 2014 were collected. Immunohistochemical staining was subsequently performed to determine the expression of LMO3 in EC tissues and its association with the clinicopathological features of patients. SPSS was used to plot the survival curve

and COX multivariate regression analysis was also adopted. In addition

LMO3 overexpression was conducted in EC cells to verify its effect on tumor cell migration.

Results

According to the analysis of TCGA database

the overall survival and disease-free survival of patients with high LMO3 expression were significantly shorter than those of low LMO3 expression(

0.05)

and the expression level of LMO3 in patients with TP53 mutation was remarkably higher than that in TP53 wild-type patients. GeneMANIA and STRING analyses showed that the main genes interacting with LMO3 included NHLH2 and LDB2. Moreover

immunohistochemical staining also indicated that patients with higher LMO3 expression level had shorter disease-free survival (

=0.005)

and multivariate COX analysis suggested LMO3 as a prognostic factor for EC. Finally

overexpression of LMO3 enhanced the migration of EC cells.

Conclusion

EC patients with high LMO3 level have a poor prognosis

which may be related to the migration of EC cells promoted by LMO3 overexpression.

关键词

Keywords

references

AMANT F, MOERMAN P, NEVEN P, et al . Endometrial cancer[J ] . Lancet, 2005, 366(9484): 491-505. DOI: 10.1016/S0140-6736(05)67063-8.

NJOKU K, CHIASSERINI D, WHETTON A D, et al . Proteomic biomarkers for the detection of endometrial cancer[J ] . Cancers, 2019, 11(10): 1572. DOI: 10.3390/cancers11101572.

CREUTZBERG C L, VAN PUTTEN W L J, KOPER P C, et al . Survival after relapse in patients with endometrial cancer: results from a randomized trial[J ] . Gynecol Oncol, 2003, 89(2): 201-209. DOI: 10.1016/S0090-8258(03)00126-4.

SHANG P, MENG F L, LIU Y D, et al . Overexpression of ANCCA/ATAD2 in endometrial carcinoma and its correlation with tumor progression and poor prognosis[J ] . Tumor Biol, 2015, 36(6): 4479-4485. DOI: 10.1007/s13277-015-3089-8.

APLAN P D, JONES C A, CHERVINSKY D S, et al . An scl gene product lacking the transactivation domain induces bony abnormalities and cooperates with LMO1 to generate T-cell malignancies in transgenic mice[J ] . EMBO J, 1997, 16(9): 2408-2419. DOI: 10.1093/emboj/16.9.2408.

SUM E Y, SEGARA D, DUSCIO B, et al . Overexpression of LMO4 induces mammary hyperplasia, promotes cell invasion, and is a predictor of poor outcome in breast cancer[J ] . Proc Natl Acad Sci USA, 2005, 102(21): 7659-7664. DOI: 10.1073/pnas.0502990102.

AOYAMA M, OZAKI T, INUZUKA H, et al . LMO3 interacts with neuronal transcription factor, HEN2, and Acts as an oncogene in neuroblastoma[J ] . Cancer Res, 2005, 65(11): 4587-4597. DOI: 10.1158/0008-5472. can-04-4630.

LARSEN S, YOKOCHI T, ISOGAI E, et al . LMO3 interacts with p53 and inhibits its transcriptional activity[J ] . Biochem Biophys Res Commun, 2010, 392(3): 252-257. DOI: 10.1016/j.bbrc.2009.12.010.

BOUTELLE A M, ATTARDI L D. p53 and tumor suppression: it takes a network[J]. Trends Cell Biol, 2021, 31(4): 298-310. DOI: 10.1016/j.tcb.2020.12.011.

何勇, 范士志, 蒋耀光. p53基因家族研究进展[J]. 第三军医大学学报, 2000, 22(12): 1215-1217. DOI: 10.16016/j.1000-5404.2000.12.041.

HE Y, FAN S Z, JIANG Y G. Progress of p53 gene family[J]. Acta Acad Med Mil Tertiae, 2000, 22(12): 1215-1217. DOI: 10.16016/j.1000-5404.2000.12.041.

LAX S F. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification[J]. Virchows Arch, 2004, 444(3): 213-223. DOI: 10.1007/s00428-003-0947-3.

MATTHEWS J M, LESTER K, JOSEPH S, et al . LIM-domain-only proteins in cancer[J ] . Nat Rev Cancer, 2013, 13(2): 111-122. DOI: 10.1038/nrc3418.

CHENG Y, HOU T L, PING J, et al . LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis inhibition by directly interacting with LATS1 and suppressing Hippo signaling[J ] . J Exp Clin Cancer Res, 2018, 37(1): 1-12. DOI: 10.1186/s13046-018-0903-3.

QIU Y S, JIANG N N, ZHOU Y, et al . LMO3 promotes gastric cancer cell invasion and proliferation through Akt-mTOR and Akt-GSK3β signaling[J ] . Int J Mol Med, 2018, 41(5): 2755-2763. DOI: 10.3892/ijmm.2018.3476.

WATANABE H, FRANCIS J M, WOO M S, et al . Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target[J ] . Genes Dev, 2013, 27(2): 197-210. DOI: 10.1101/gad.203208.112.

ENGELSEN I B, AKSLEN L A, SALVESEN H B. Biologic markers in endometrial cancer treatment[J]. APMIS, 2009, 117(10): 693-707. DOI: 10.1111/j.1600-0463.2009.02467.x.

黄洁, 李聪, 李云云, 等. PDZK1在子宫内膜癌中的表达及临床意义[J]. 第三军医大学学报, 2019, 41(3): 259-264. DOI: 10.16016/j.1000-5404.201809041.

HUANG J, LI C, LI YY, et al . Expression of PDZK1 in endometrial carcinoma and its clinical si gnificance[J ] . J Third Mil Med Univ, 2019, 41(3): 259-264. DOI: 10.16016/j.1000-5404.201809041.

ANGIOLI R, CAPRIGLIONE S, SCALETTA G, et al . The role of HE4 in endometrial cancer recurrence: how to choose the optimal follow-up program[J ] . Tumour Biol, 2016, 37(4): 4973-4978. DOI: 10.1007/s13277-015-4324-z.

LO S S, KHOO U S, CHENG D K, et al . Role of serial tumor markers in the surveillance for recurrence in endometrial cancer[J ] . Cancer Detect Prev, 1999, 23(5): 397-400. DOI: 10.1046/j.1525-1500.1999.99043.x.

GOOD D J, COYLE C A, FOX D L. Nhlh2: a basic helix-loop-helix transcription factor controlling physical activity[J]. Exerc Sport Sci Rev, 2008, 36(4): 187-192. DOI: 10.1097/jes.0b013e31818782dd.

WAGNER G, FENZL A, LINDROOS-CHRISTENSEN J, et al . LMO3 reprograms visceral adipocyte metabolism during obesity[J ] . J Mol Med, 2021, 99(8): 1151-1171. DOI: 10.1007/s00109-021-02089-9.

LINDROOS J, HUSA J L, MITTERER G, et al . Human but not mouse adipogenesis is critically dependent on LMO3[J ] . Cell Metab, 2013, 18(1): 62-74. DOI: 10.1016/j.cmet.2013.05.0 20.

AUSTIN H, AUSTIN JR J M, PARTRIDGE E E, et al . Endometrial cancer, obesity, and body fat distribution[J ] . Cancer Res, 1991, 51(2): 568-572.

YU H Y, JIA R C, ZHAO L, et al . LDB2 inhibits proliferation and migration in liver cancer cells by abrogating HEY1 expression[J ] . Oncotarget, 2017, 8(55): 94440-94449. DOI: 10.18632/oncotarget.21772.

STORBECK C J, WAGNER S, O'REILLY P, et al . The Ldb1 and Ldb2 transcriptional cofactors interact with the Ste20-like kinase SLK and regulate cell migration[J ] . MBoC, 2009, 20(19): 4174-4182. DOI: 10.1091/mbc.e08-07-0707.

杨楠, 陈天翔, 刘润坤, 等. IFIT5在肝细胞癌中表达上调并促进肝癌细胞侵袭和迁移[J]. 第三军医大学学报, 2020, 42(21): 2093-2099. DOI: 10.16016/j.1000-5404.202005290.

YANG N, CHEN T X, LIU R K, et al . Enhanced expression of interferon-induced protein with tetratricopeptide repeats 5 promotes migration and invasion of hepatocellular carcinoma cells[J ] . J Third Mil Med Univ, 2020, 42(21): 2093-2099. DOI: 10.16016/j.1000-5404.202005290.

XUAN Y W, LIAO M, ZHAI W L, et al . MicroRNA-381 inhibits lung adenocarcinoma cell biological progression by directly targeting LMO3 through regulation of the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition[J ] . Eur Rev Med Pharmacol Sci, 2019, 23(19): 8411-8421. DOI: 10.26355/eurrev_201910_19152.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Features of tumor cells and microenvironment associated with recurrence risk of mesenchymal-subtype gastric cancer based on bulk RNA-seq and scRNA-seq

Identification of hub genes associated with prognosis of gastric cancer by integrated bioinformatics analysis

A novel estrogen receptor expression stratification (low/moderate/high) based on Chinese population provides more accurate prognosis prediction for HR⁺/HER2^- early breast cancer patients

Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance

Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases

Related Author

PAN Yuwei

TAN Yuting

XUE Rui

CHU Zhaole

LIU Biying

LI Xianfeng

WANG Tao

WANG Bin

Related Institution

School of Medicine， Chongqing University

Department of Gastroenterology， Chongqing University Cancer Hospital

Department of Gastroenterology， Chongqing Key Laboratory of Precise Prevention and Treatment of Digestive Malignancies， Army Medical Center of PLA/Daping Hospital of Third Military Medical University

Department of Oncology， Chongqing Hospital of Traditional Chinese Medicine

Molecular and Tumor Research Center, College of Basic Medical Sciences, Chongqing Medical University

⁰