Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Adrenocortical Carcinoma | Research

ESCO2’s oncogenic role in human tumors: a pan-cancer analysis and experimental validation

Authors: Yue Huang, Dapeng Chen, Yi Bai, Yamin Zhang, Zhiwen Zheng, Qingfeng Fu, Bocun Yi, Yuchen Jiang, Zhihong Zhang, Jianqiang Zhu

Published in: BMC Cancer | Issue 1/2024

Login to get access

Abstract

Purpose

Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function.

Methods

We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2’s impacts on clear cell renal cell carcinoma (ccRCC) cells’ proliferative and invasive capacities in vitro.

Results

In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2’S knockdown significantly inhibited the A498 and T24 cells’ proliferation, invasion, and migration.

Conclusions

In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.
Appendix
Available only for authorised users
Literature
1.
Bray F, Laversanne M, Weiderpass E, Soerjomataram I. The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer. 2021;127(16):3029–30.PubMedCrossRef
2.
Sung H, Ferlay J, Siegel RL, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.PubMedCrossRef
3.
Finn RS, Martin M, Rugo HS, et al. Palbociclib and Letrozole in Advanced breast Cancer. N Engl J Med. 2016;375(20):1925–36.PubMedCrossRef
4.
Matthews HK, Bertoli C, de Bruin R. Cell cycle control in cancer. Nat Rev Mol Cell Biol. 2022;23(1):74–88.PubMedCrossRef
5.
Weiss JM, Csoszi T, Maglakelidze M, et al. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019;30(10):1613–21.PubMedPubMedCentralCrossRef
6.
7.
8.
Wang R, Xu K, Gao F, Huang J, Guan X. Clinical considerations of CDK4/6 inhibitors in triple-negative breast cancer. Biochim Biophys Acta Rev Cancer. 2021;1876(2):188590.PubMedCrossRef
9.
Liu Z, Cheng X, Pang B, et al. Effects of ESCO2 or its methylation on the prognosis, clinical characteristics, immune microenvironment, and pathogenesis of low-grade glioma. Int Immunopharmacol. 2022;104:108399.PubMedCrossRef
10.
Bender D, Da Silva E, Chen J, et al. Multivalent interaction of ESCO2 with the replication machinery is required for sister chromatid cohesion in vertebrates. Proc Natl Acad Sci U S A. 2020;117(2):1081–9.PubMedCrossRef
11.
Vega H, Waisfisz Q, Gordillo M, et al. Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion. Nat Genet. 2005;37(5):468–70.PubMedCrossRef
12.
13.
Michaelis C, Ciosk R, Nasmyth K. Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell. 1997;91(1):35–45.PubMedCrossRef
14.
Guacci V, Koshland D, Strunnikov A. A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. Cerevisiae. Cell. 1997;91(1):47–57.PubMedPubMedCentralCrossRef
15.
Wang QL, Liu L. Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma. J Clin Lab Anal. 2020;34(5):e23163.PubMedPubMedCentralCrossRef
16.
Zhu HE, Li T, Shi S, Chen DX, Chen W, Chen H. ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation. J Exp Clin Cancer Res. 2021;40(1):64.PubMedPubMedCentralCrossRef
17.
Chen H, Zhang L, He W, et al. ESCO2 knockdown inhibits cell proliferation and induces apoptosis in human gastric cancer cells. Biochem Biophys Res Commun. 2018;496(2):475–81.PubMedCrossRef
18.
Zhang T, Wang B, Gu B et al. Genetic and Molecular Characterization Revealed the Prognosis Efficiency of Histone Acetylation in Pan-Digestive Cancers. J Oncol. 2022. 2022: 3938652.
19.
Guo XB, Huang B, Pan YH, Su SG, Li Y. ESCO2 inhibits tumor metastasis via transcriptionally repressing MMP2 in colorectal cancer. Cancer Manag Res. 2018;10:6157–66.PubMedPubMedCentralCrossRef
20.
Fu J, Zhou S, Xu H, et al. ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex. Nucleic Acids Res. 2023;51(14):7376–91.PubMedPubMedCentralCrossRef
21.
22.
The GTEx. Consortium atlas of genetic regulatory effects across human tissues. Science. 2020;369(6509):1318–30.CrossRef
23.
Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The Molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst. 2015;1(6):417–25.PubMedPubMedCentralCrossRef
24.
Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.PubMedPubMedCentralCrossRef
25.
26.
27.
28.
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–92.PubMedCrossRef
29.
Zhang M, Zhai W, Miao J, et al. Single cell analysis reveals intra-tumour heterogeneity, microenvironment and potential diagnosis markers for clear cell renal cell carcinoma. Clin Transl Med. 2022;12(5):e713.PubMedPubMedCentralCrossRef
30.
Izadi S, Nikkhoo A, Hojjat-Farsangi M, et al. CDK1 in breast Cancer: implications for theranostic potential. Anticancer Agents Med Chem. 2020;20(7):758–67.PubMedCrossRef
31.
Ren L, Yang Y, Li W, et al. CDK1 serves as a therapeutic target of adrenocortical carcinoma via regulating epithelial-mesenchymal transition, G2/M phase transition, and PANoptosis. J Transl Med. 2022;20(1):444.PubMedPubMedCentralCrossRef
32.
33.
Deng J, Wang ES, Jenkins RW, et al. CDK4/6 inhibition augments Antitumor Immunity by enhancing T-cell activation. Cancer Discov. 2018;8(2):216–33.PubMedCrossRef
34.
Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004;3(11):1427–38.PubMedCrossRef
35.
Diamond JR, Boni V, Lim E, et al. First-in-human dose-escalation study of cyclin-dependent kinase 9 inhibitor VIP152 in patients with Advanced malignancies shows early signs of clinical efficacy. Clin Cancer Res. 2022;28(7):1285–93.PubMedCrossRef
36.
Kumar SK, LaPlant B, Chng WJ, et al. Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015;125(3):443–8.PubMedPubMedCentralCrossRef
37.
Fang H, Sheng S, Chen B, et al. A Pan-cancer analysis of the oncogenic role of Cell Division Cycle-Associated protein 4 (CDCA4) in human tumors. Front Immunol. 2022;13:826337.PubMedPubMedCentralCrossRef
38.
Xiang C, Sun WH, Ke Y, Yu X, Wang Y. CDCA8 contributes to the development and progression of thyroid Cancer through regulating CDK1. J Cancer. 2022;13(7):2322–35.PubMedPubMedCentralCrossRef
39.
Wei S, Dai M, Zhang C, et al. KIF2C: a novel link between Wnt/β-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma. Protein Cell. 2021;12(10):788–809.PubMedCrossRef
40.
Alomer RM, da Silva E, Chen J, et al. Esco1 and Esco2 regulate distinct cohesin functions during cell cycle progression. Proc Natl Acad Sci U S A. 2017;114(37):9906–11.PubMedPubMedCentralCrossRef
41.
Sun H, Zhang J, Xin S, et al. Cul4-Ddb1 ubiquitin ligases facilitate DNA replication-coupled sister chromatid cohesion through regulation of cohesin acetyltransferase Esco2. PLoS Genet. 2019;15(2):e1007685.PubMedPubMedCentralCrossRef
42.
Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature. 2001;411(6835):342–8.PubMedCrossRef
43.
Santamaría D, Barrière C, Cerqueira A, et al. Cdk1 is sufficient to drive the mammalian cell cycle. Nature. 2007;448(7155):811–5.PubMedCrossRef
44.
Sofi S, Mehraj U, Qayoom H, et al. Targeting cyclin-dependent kinase 1 (CDK1) in cancer: molecular docking and dynamic simulations of potential CDK1 inhibitors. Med Oncol. 2022;39(9):133.PubMedPubMedCentralCrossRef
45.
Wu CX, Wang XQ, Chok SH, et al. Blocking CDK1/PDK1/β-Catenin signaling by CDK1 inhibitor RO3306 increased the efficacy of sorafenib treatment by targeting cancer stem cells in a preclinical model of hepatocellular carcinoma. Theranostics. 2018;8(14):3737–50.PubMedPubMedCentralCrossRef
46.
Wu J, Yuan Y, Long Priel DA, et al. Phase I study of Zotiraciclib in Combination with Temozolomide for patients with recurrent high-grade Astrocytomas. Clin Cancer Res. 2021;27(12):3298–306.PubMedPubMedCentralCrossRef
47.
O’Neil BH, Scott AJ, Ma WW, et al. A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer. Ann Oncol. 2015;26(9):1923–9.PubMedPubMedCentralCrossRef
48.
Zhang J, Bu X, Wang H, et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature. 2018;553(7686):91–5.PubMedCrossRef
Metadata
Title
ESCO2’s oncogenic role in human tumors: a pan-cancer analysis and experimental validation
Authors
Yue Huang
Dapeng Chen
Yi Bai
Yamin Zhang
Zhiwen Zheng
Qingfeng Fu
Bocun Yi
Yuchen Jiang
Zhihong Zhang
Jianqiang Zhu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12213-w

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue

Study Protocol

Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients – a randomized controlled trial. (OxaNeuro)

Research

Imaging diagnosis and differential diagnosis of extraskeletal osteosarcoma

Study Protocol

iCare – a self-directed, interactive online program to improve health and wellbeing for people living with upper gastrointestinal or hepato-pancreato-biliary cancers, and their informal carers: the study protocol for a Phase II randomised controlled trial

Research

MUC1 promotes cervical squamous cell carcinoma through ERK phosphorylation-mediated regulation of ITGA2/ITGA3

Research

The radiological characteristics, tertiary lymphoid structures, and survival status associated with EGFR mutation in patients with subsolid nodules like stage I-II LUAD.

Research

Knockdown of CENPM activates cGAS-STING pathway to inhibit ovarian cancer by promoting pyroptosis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits