Clinical Significance of cfRNAs as Tumor Biomarkers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 2747

Special Issue Editor


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Guest Editor
Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece
Interests: circulating tumor cells; miRNAs; cfDNA; gene expression; methylation; mutations; development of sensitive molecular assays
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Special Issue Information

Dear Colleagues,

The investigation of cfRNA in plasma to monitor disease is a rapidly growing area of diagnostic research. Circulating cfRNA in the blood is released from cells by active secretion, or through apoptosis or necrosis. cfRNA presents an opportunity to detect cancer in patients with low tumor-shedding rates, as the overexpression of tumor-specific transcripts could lead to the amplification of tumor-derived RNAs in the blood. Increasing evidence shows that long RNA species, including messenger RNA (mRNA), circular RNA (circRNA), and long noncoding RNAs (lncRNA), are also found in human blood and have functional and clinical implications. 

Within this context, this Special Issue aims to advance the emerging standpoint on the importance of holistic knowledge of cfRNA as a tumor biomarker. Therefore, authors are invited to submit original research and review papers that are focused on, but not limited to, the following topics:

  • The clinical scope of cfRNA as a biomarker;
  • Preanalytical optimization, standardization, and quality control;
  • Exciting applications of cfRNA analysis in oncology;
  • The use of cfRNA as a tool for early cancer detection;
  • Monitoring minimal residual disease in cancer by using cfRNA biomarkers;
  • Comparative analysis of methods and technologies for the detection of cfRNA;
  • Enrichment strategies for circulating tumor cfRNA (extraction methods);
  • The use of RNA sequencing (RNA-seq) to investigate the vast diversity of RNA species.

Dr. Athina N. Markou
Guest Editor

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Keywords

  • cfRNAs
  • circRNAs
  • lncRNAs
  • cancer biomarkers
  • discovery of new RNA species
  • enrichment methods
  • preanalytical issues in cfRNA

Published Papers (2 papers)

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Research

18 pages, 21117 KiB  
Article
Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies
by Pawel Zayakin, Lilite Sadovska, Kristaps Eglītis, Nadezhda Romanchikova, Ilze Radoviča-Spalviņa, Edgars Endzeliņš, Inta Liepniece-Karele, Jānis Eglītis and Aija Linē
Cancers 2023, 15(17), 4329; https://doi.org/10.3390/cancers15174329 - 30 Aug 2023
Cited by 1 | Viewed by 1226
Abstract
Over the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, [...] Read more.
Over the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, we performed deep sequencing of plasma EV RNA cargo in 32 patients with locally advanced breast cancer (BC) at diagnosis and 7 days after breast surgery and in 30 cancer-free healthy controls (HCs). To identify BC-derived RNA biomarkers, we searched for RNAs that had higher levels in BC EVs at the time of diagnosis compared with HCs and decreased after surgery. Data analysis showed that the fractions of miRNAs, snRNAs, snoRNAs, and tRFs were increased, but the fraction of lncRNAs was decreased in BC EVs as compared to HCs. BC-derived biomarker candidates were identified across various RNA biotypes. Considered individually, they had very high specificity but moderate sensitivity for the detection of BC, whereas a biomarker model composed of eight RNAs: SNORD3H, SNORD1C, SNORA74D, miR-224-5p, piR-32949, lnc-IFT-122-2, lnc-C9orf50-4, and lnc-FAM122C-3 was able to distinguish BC from HC EVs with an AUC of 0.902 (95% CI = 0.872–0.931, p = 3.4 × 10−9) in leave-one-out cross-validation. Furthermore, a number of RNA biomarkers were correlated with the ER and HER2 expression and additional biomarker models were created to predict hormone receptor and HER2 status. Overall, this study demonstrated that the RNA composition of plasma EVs is altered in BC patients and that they contain cancer-derived RNA biomarkers that can be used for BC detection and monitoring using liquid biopsies. Full article
(This article belongs to the Special Issue Clinical Significance of cfRNAs as Tumor Biomarkers)
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17 pages, 3286 KiB  
Article
Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer
by Stephanie H. Lim, Wei Chua, Weng Ng, Emilia Ip, Tania M. Marques, Nham T. Tran, Margarida Gama-Carvalho, Ray Asghari, Christopher Henderson, Yafeng Ma, Paul de Souza and Kevin J. Spring
Cancers 2023, 15(16), 4184; https://doi.org/10.3390/cancers15164184 - 20 Aug 2023
Cited by 1 | Viewed by 1194
Abstract
Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/− chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in [...] Read more.
Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/− chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM (Fluxion Biosciences Inc., Alameda, CA, USA) CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline; numbers fell and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points, three microRNAs (hsa-miR-95, hsa-miR-10a, and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. These miRNAs represent potential predictive biomarkers, and thus a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early-stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response. Full article
(This article belongs to the Special Issue Clinical Significance of cfRNAs as Tumor Biomarkers)
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