Extracellular vesicle-based liquid biopsy holds great promise for the management of ovarian cancer

Amongst the various gynecological malignancies affecting female health globally, ovarian cancer is one of the predominant and lethal among all. The identification and functional characterization of long non-coding RNAs (lncRNAs) are made possible with the advent of RNA-seq and the advancement of computational logarithm in understanding human disease biology. LncRNAs can interact with deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins and their combinations. Moreover, lncRNAs regulate orchestra of diverse functions including chromatin organization and transcriptional and post-transcriptional regulation. LncRNAs have conferred their critical role in key biological processes in human cancer including tumor initiation, proliferation, cell cycle, apoptosis, necroptosis, autophagy, and metastasis. The interwoven function of tumor-suppressor protein p53-linked lncRNAs in the ovarian cancer paradigm is of paramount importance. Several lncRNAs operate as p53 regulators or effectors and modulates a diverse array of functions either by participating in various signaling cascades or via interaction with different proteins. This review highlights the recent progress made in the identification of p53 associated lncRNAs while elucidating their molecular mechanisms behind the altered expression in ovarian cancer tumorigenesis. Moreover, the development of novel clinical and therapeutic strategies for targeting lncRNAs in human cancers harbors great promise.

Download Full-text

Early detection of hepatocellular carcinoma via liquid biopsy: panel of small extracellular vesicle‐derived long noncoding RNAs identified as markers

Molecular Oncology ◽

10.1002/1878-0261.13049 ◽

2021 ◽

Author(s):

Soon Sun Kim ◽

Geum Ok Baek ◽

Ju A Son ◽

Hye Ri Ahn ◽

Moon Kyung Yoon ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Early Detection ◽

Liquid Biopsy ◽

Noncoding Rnas ◽

Extracellular Vesicle ◽

Long Noncoding Rnas

Download Full-text

The Origin of Tumor DNA in Urine of Urogenital Cancer Patients: Local Shedding and Transrenal Excretion

Cancers ◽

10.3390/cancers13030535 ◽

2021 ◽

Vol 13 (3) ◽

pp. 535

Author(s):

Anouk E. Hentschel ◽

Rianne van den Helder ◽

Nienke E. van Trommel ◽

Annina P. van Splunter ◽

Robert A. A. van Boerdonk ◽

...

Keyword(s):

Cervical Cancer ◽

Bladder Cancer ◽

Cancer Patients ◽

Liquid Biopsy ◽

Bladder Tumor ◽

Great Promise ◽

Tumor Tissues ◽

Catheter Urine ◽

Tumor Dna ◽

Urogenital Cancers

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.

Download Full-text

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

AJP Cell Physiology ◽

10.1152/ajpcell.00048.2021 ◽

2021 ◽

Author(s):

Dan Li ◽

Wenjia Lai ◽

Di Fan ◽

Qiaojun Fang

Keyword(s):

Breast Cancer ◽

Early Diagnosis ◽

Extracellular Vesicles ◽

Liquid Biopsy ◽

Breast Cancer Diagnosis ◽

Extracellular Vesicle ◽

Detection Methods ◽

Protein Markers ◽

Liquid Biopsies ◽

Diagnosis And Prognosis

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their non-invasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.

Download Full-text

Potential clinical applications of circulating cell-free DNA in ovarian cancer patients

Expert Reviews in Molecular Medicine ◽

10.1017/erm.2018.5 ◽

2018 ◽

Vol 20 ◽

Cited By ~ 4

Author(s):

Ana Barbosa ◽

Ana Peixoto ◽

Pedro Pinto ◽

Manuela Pinheiro ◽

Manuel R. Teixeira

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Liquid Biopsy ◽

Clinical Applications ◽

Epigenetic Alterations ◽

Cell Free Dna ◽

Non Invasive ◽

Free Dna ◽

Potential Use ◽

Circulating Cell Free Dna

AbstractCirculating cell-free DNA (cfDNA) consists of small fragments of DNA that circulate freely in the bloodstream. In cancer patients, a fraction of cfDNA is derived from tumour cells, therefore containing the same genetic and epigenetic alterations, and is termed circulating cell-free tumour DNA. The potential use of cfDNA, the so-called ‘liquid biopsy’, as a non-invasive cancer biomarker has recently received a lot of attention. The present review will focus on studies concerning the potential clinical applications of cfDNA in ovarian cancer patients.

Download Full-text

Extracellular vesicle-associated miRNAs in ovarian cancer – design of an integrated NGS-based workflow for the identification of blood-based biomarkers for platinum-resistance

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-1048 ◽

2019 ◽

Vol 57 (7) ◽

pp. 1053-1062 ◽

Cited By ~ 14

Author(s):

Jan Dominik Kuhlmann ◽

Issam Chebouti ◽

Rainer Kimmig ◽

Paul Buderath ◽

Michael Reuter ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Independent Set ◽

Extracellular Vesicle ◽

Platinum Resistance ◽

Diagnostic Purpose ◽

Illumina Platform ◽

Platinum Sensitive ◽

Platinum Resistant ◽

Next Generation Sequencing Ngs

AbstractBackgroundExtracellular vesicle (EV)-associated microRNAs (miRNAs) have been suggested as promising biomarkers for blood-based cancer diagnosis. However, one of the major limitations for the use of EVs with diagnostic purpose is the lack of standardized EV-profiling techniques. In this regard, the objective of our study was to design an integrated next-generation sequencing (NGS)-based workflow for analyzing the signature of EV-associated miRNA in the plasma of platinum-resistant ovarian cancer patients.MethodsFor EV-extraction, different enrichment methods were compared (ExoQuick vs. exoRNeasy). NGS was performed with the Illumina platform.ResultsWe established an integrated NGS-based workflow, including EV-enrichment with the ExoQuick system, which resulted in an optimal RNA-yield and consistent small RNA libraries. We applied this workflow in a pilot cohort of clinically documented platinum-sensitive (n=15) vs. platinum-resistant (n=15) ovarian cancer patients, resulting in a panel of mature EV-associated miRNAs (including ovarian cancer associated miR-181a, miR-1908, miR-21, miR-486 and miR-223), which were differentially abundant in the plasma of platinum-resistant patients.ConclusionsThis is the first study, analyzing the profile of EV-associated miRNAs in platinum-resistant ovarian cancer patients. We provide rationale to further validate these miRNA candidates in an independent set of patients, in order to characterize their biomarker potential as predictors for platinum-resistance.

Download Full-text

Liquid biopsy in ovarian cancer: the potential of circulating miRNAs and exosomes

Translational Research ◽

10.1016/j.trsl.2018.10.003 ◽

2019 ◽

Vol 205 ◽

pp. 77-91 ◽

Cited By ~ 32

Author(s):

Lydia Giannopoulou ◽

Martha Zavridou ◽

Sabine Kasimir-Bauer ◽

Evi S. Lianidou

Keyword(s):

Ovarian Cancer ◽

Liquid Biopsy ◽

Circulating Mirnas

Download Full-text