Circulating Serum Exosomal AHIF is a Novel Prognostic Predictor for Epithelial Ovarian Cancer

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Oct 2

PMID 31571921

Citations 17

Authors

Xiaoyan Tang

Songping Liu

Yinglei Liu

Xiaojing Lin

Tingting Zheng

Xin Liu

Junjun Qiu

Keqin Hua

Affiliations

Soon will be listed here.

Abstract

Purpose: Exosomes are key mediators of cellular communication by transporting molecules, including long noncoding RNAs (lncRNAs), and have been regarded as promising non-invasive biomarkers. This study aimed to evaluate the expression pattern and clinical significance of serum exosomal lncRNA antisense hypoxia inducible factor (aHIF) in epithelial ovarian cancer (EOC).

Patients And Methods: Sixty-two EOC patients in Obstetrics and Gynecology Hospital of Fudan University were enrolled. The expression levels of aHIF in tissues and serum exosomes were examined by RT-qPCR. The origin of serum exosomal aHIF was explored in vitro and in vivo. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic factors of EOC. A prognostic predictive nomogram was formulated in R software.

Results: We isolated exosomes, identified exosomal aHIF in the serum of EOC patients. The expression of serum exosomal aHIF was higher in EOC patients and was correlated with the aHIF level in EOC tissues. In vitro and in vivo, the results indicated that serum exosomal aHIF was derived from tumor cells. Kaplan-Meier survival analysis demonstrated that EOC patients with higher serum exosomal aHIF expression had poorer overall survival. Cox multivariate regression model revealed that FIGO stage, residual tumor size, and serum exosomal aHIF level were independent prognostic factors of EOC. Based on the prognostic value of serum exosomal aHIF, we established a nomogram model that showed a good predictive ability for EOC patients.

Conclusion: Serum exosomal aHIF is overexpressed in EOC and can serve as a noninvasive predictive biomarker for unfavorable prognosis.

Citing Articles

Advances in small extracellular vesicles: roles in the tumor microenvironment and epithelial ovarian cancer diagnosis and treatment.

Peng L, Lai Y, Cao B Front Oncol. 2025; 15:1526944.

PMID: 40008006 PMC: 11850269. DOI: 10.3389/fonc.2025.1526944.

Investigating the role of exosomal long non-coding RNAs in drug resistance within female reproductive system cancers.

Shirani N, Abdi N, Chehelgerdi M, Yaghoobi H, Chehelgerdi M Front Cell Dev Biol. 2025; 13:1485422.

PMID: 39925739 PMC: 11802832. DOI: 10.3389/fcell.2025.1485422.

The roles of long non-coding RNAs in ovarian cancer: from functions to therapeutic implications.

Hu Z, Yuan L, Yang X, Yi C, Lu J Front Oncol. 2024; 14:1332528.

PMID: 38725621 PMC: 11079149. DOI: 10.3389/fonc.2024.1332528.

Exosomal Cargo in Ovarian Cancer Dissemination.

Dzhugashvili E, Tamkovich S Curr Issues Mol Biol. 2023; 45(12):9851-9867.

PMID: 38132461 PMC: 10742327. DOI: 10.3390/cimb45120615.

Unlocking Exosome-Based Theragnostic Signatures: Deciphering Secrets of Ovarian Cancer Metastasis.

Mukherjee S, Nag S, Mukerjee N, Maitra S, Muthusamy R, Fuloria N ACS Omega. 2023; 8(40):36614-36627.

PMID: 37841156 PMC: 10568589. DOI: 10.1021/acsomega.3c02837.

References

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

Jandura A, Krause H . The New RNA World: Growing Evidence for Long Noncoding RNA Functionality. Trends Genet. 2017; 33(10):665-676. DOI: 10.1016/j.tig.2017.08.002. View

Huitzil-Melendez F, Capanu M, OReilly E, Duffy A, Gansukh B, Saltz L . Advanced hepatocellular carcinoma: which staging systems best predict prognosis?. J Clin Oncol. 2010; 28(17):2889-95. PMC: 3651603. DOI: 10.1200/JCO.2009.25.9895. View

Rossignol F, Vache C, Clottes E . Natural antisense transcripts of hypoxia-inducible factor 1alpha are detected in different normal and tumour human tissues. Gene. 2002; 299(1-2):135-40. DOI: 10.1016/s0378-1119(02)01049-1. View

Span P, Rao J, Oude Ophuis S, Lenders J, Sweep F, Wesseling P . Overexpression of the natural antisense hypoxia-inducible factor-1alpha transcript is associated with malignant pheochromocytoma/paraganglioma. Endocr Relat Cancer. 2011; 18(3):323-31. DOI: 10.1530/ERC-10-0184. View

Szajnik M, Czystowska-Kuzmicz M, Elishaev E, Whiteside T . Biological markers of prognosis, response to therapy and outcome in ovarian carcinoma. Expert Rev Mol Diagn. 2016; 16(8):811-26. PMC: 5010004. DOI: 10.1080/14737159.2016.1194758. View

Kalra H, Adda C, Liem M, Ang C, Mechler A, Simpson R . Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma. Proteomics. 2013; 13(22):3354-64. DOI: 10.1002/pmic.201300282. View

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

Chen M, Zhuang C, Liu Y, Li J, Dai F, Xia M . Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer. Cancer Lett. 2016; 376(1):155-64. DOI: 10.1016/j.canlet.2016.03.037. View

10.

Milane L, Singh A, Mattheolabakis G, Suresh M, Amiji M . Exosome mediated communication within the tumor microenvironment. J Control Release. 2015; 219:278-294. DOI: 10.1016/j.jconrel.2015.06.029. View

11.

Pan B, Johnstone R . Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983; 33(3):967-78. DOI: 10.1016/0092-8674(83)90040-5. View

12.

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

13.

Chen W, Huang M, Kong R, Xu T, Zhang E, Xia R . Antisense Long Noncoding RNA HIF1A-AS2 Is Upregulated in Gastric Cancer and Associated with Poor Prognosis. Dig Dis Sci. 2015; 60(6):1655-62. DOI: 10.1007/s10620-015-3524-0. View

14.

Shao Y, Ning Z, Chen J, Geng Y, Gu W, Huang J . Prognostic nomogram integrated systemic inflammation score for patients with esophageal squamous cell carcinoma undergoing radical esophagectomy. Sci Rep. 2015; 5:18811. PMC: 4686940. DOI: 10.1038/srep18811. View

15.

Meerang M, Boss A, Kenkel D, Broggini-Tenzer A, Berard K, Lauk O . Evaluation of imaging techniques for the assessment of tumour progression in an orthotopic rat model of malignant pleural mesothelioma†. Eur J Cardiothorac Surg. 2014; 47(1):e34-41. DOI: 10.1093/ejcts/ezu393. View

16.

Cappello F, Logozzi M, Campanella C, Caruso Bavisotto C, Marcilla A, Properzi F . Exosome levels in human body fluids: A tumor marker by themselves?. Eur J Pharm Sci. 2016; 96:93-98. DOI: 10.1016/j.ejps.2016.09.010. View

17.

Kim S, Yoon M, Park Y, Kim M, Nam B, Park S . Nomograms predicting survival of patients with unresectable or metastatic gastric cancer who receive combination cytotoxic chemotherapy as first-line treatment. Gastric Cancer. 2017; 21(3):453-463. DOI: 10.1007/s10120-017-0756-z. View

18.

Zhao R, Zhang Y, Zhang X, Yang Y, Zheng X, Li X . Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer. Mol Cancer. 2018; 17(1):68. PMC: 6389063. DOI: 10.1186/s12943-018-0817-x. View

19.

Alegre E, Zubiri L, Perez-Gracia J, Gonzalez-Cao M, Soria L, Martin-Algarra S . Circulating melanoma exosomes as diagnostic and prognosis biomarkers. Clin Chim Acta. 2016; 454:28-32. DOI: 10.1016/j.cca.2015.12.031. View

20.

Liu T, Zhang X, Gao S, Jing F, Yang Y, Du L . Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer. Oncotarget. 2016; 7(51):85551-85563. PMC: 5356757. DOI: 10.18632/oncotarget.13465. View