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Cancers
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Liquid Biopsy in Gastrointestinal Cancers
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Liquid Biopsy in Gastrointestinal Cancers

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

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 13921

Special Issue Editors

Dr. Julie Earl

E-Mail Website
Guest Editor
Molecular Epidemiology and Predictive Tumor Markers Group, Medical Oncology Research Laboratory, Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9100, 28034 Madrid, Spain
Interests: pancreatic cancer; cancer genetics; biomarkers; liquid biopsy; cell-free DNA
Special Issues, Collections and Topics in MDPI journals
Dr. Bozena Smolkova

E-Mail Website
Guest Editor
Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, 845 05 Bratislava, Slovakia
Interests: genetics; epigenetics; pancreatic cancer; uveal melanoma; liquid biopsy
Special Issues, Collections and Topics in MDPI journals
Dr. Agapi Kataki

E-Mail Website
Guest Editor
1st Department of Propaedeutic Surgery, Hippocration Hospital, Athens Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: apoptosis; autophagy; senescence; tumor microenvironment; cancer genetics; metastasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liquid biopsies are of upmost importance in many cancer types due to the limited availability of the fresh tissue needed to perform molecular studies; in addition, this technique avoids the need for invasive tissue sampling. Furthermore, the need for new and effective biomarkers for early detection and patient monitoring is an important unmet clinical need in many digestive cancers such as pancreatic and gastric cancer. This issue will focus on topics concerning the use of liquid biopsies in all digestive tumors, including, but not limited to, early detection markers, novel treatment strategies and disease monitoring. Liquid biopsy marker studies may include the use of circulating nucleic acids, circulating tumor cells, metabolomics, methylation and microbiome markers, among others. Furthermore, studies using non-blood liquid biopsy samples such as saliva, feces and cyst fluid are highly encouraged, as well as studies focusing on pre-diagnostic cohorts. Review articles concerning the current state of the art and the future perspectives of liquid biopsies in digestive cancers are also encouraged.

Dr. Julie Earl
Dr. Bozena Smolkova
Dr. Agapi Kataki
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gastrointestinal cancer
  • pancreas cancer/pancreatic cancer
  • colorectal cancer
  • gastric cancer
  • bilary tract cancer
  • liver cancer
  • liquid biopsy
  • biomarkers
  • treatment strategies
  • treatment resistance

Published Papers (6 papers)

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Editorial

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4 pages, 208 KiB  
Editorial
Liquid Biopsy in Gastrointestinal Cancers: How Close Are We to Reaching the Clinic?
by Julie Earl, Agapi Kataki and Bozena Smolkova
Cancers 2023, 15(10), 2831; https://doi.org/10.3390/cancers15102831 - 19 May 2023
Viewed by 853
Abstract
Gastrointestinal (GI) cancers are malignancies that develop within the digestive system and account for one in four cancer cases according to WHO data [...] Full article
(This article belongs to the Special Issue Liquid Biopsy in Gastrointestinal Cancers)

Research

Jump to: Editorial, Review

25 pages, 2601 KiB  
Article
Sensitive Detection of Cell-Free Tumour DNA Using Optimised Targeted Sequencing Can Predict Prognosis in Gastro-Oesophageal Cancer
by Karin Wallander, Zahra Haider, Ashwini Jeggari, Hassan Foroughi-Asl, Anna Gellerbring, Anna Lyander, Athithyan Chozhan, Ollanta Cuba Gyllensten, Moa Hägglund, Valtteri Wirta, Magnus Nordenskjöld, Mats Lindblad and Emma Tham
Cancers 2023, 15(4), 1160; https://doi.org/10.3390/cancers15041160 - 11 Feb 2023
Cited by 6 | Viewed by 2297
Abstract
In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from [...] Read more.
In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients. Full article
(This article belongs to the Special Issue Liquid Biopsy in Gastrointestinal Cancers)
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24 pages, 4539 KiB  
Article
Patterns of Somatic Variants in Colorectal Adenoma and Carcinoma Tissue and Matched Plasma Samples from the Hungarian Oncogenome Program
by Alexandra Kalmár, Orsolya Galamb, Gitta Szabó, Orsolya Pipek, Anna Medgyes-Horváth, Barbara K. Barták, Zsófia B. Nagy, Krisztina A. Szigeti, Sára Zsigrai, István Csabai, Péter Igaz, Béla Molnár and István Takács
Cancers 2023, 15(3), 907; https://doi.org/10.3390/cancers15030907 - 31 Jan 2023
Cited by 3 | Viewed by 1874
Abstract
Analysis of circulating cell-free DNA (cfDNA) of colorectal adenoma (AD) and cancer (CRC) patients provides a minimally invasive approach that is able to explore genetic alterations. It is unknown whether there are specific genetic variants that could explain the high prevalence of CRC [...] Read more.
Analysis of circulating cell-free DNA (cfDNA) of colorectal adenoma (AD) and cancer (CRC) patients provides a minimally invasive approach that is able to explore genetic alterations. It is unknown whether there are specific genetic variants that could explain the high prevalence of CRC in Hungary. Whole-exome sequencing (WES) was performed on colon tissues (27 AD, 51 CRC) and matched cfDNAs (17 AD, 33 CRC); furthermore, targeted panel sequencing was performed on a subset of cfDNA samples. The most frequently mutated genes were APC, KRAS, and FBN3 in AD, while APC, TP53, TTN, and KRAS were the most frequently mutated in CRC tissue. Variants in KRAS codons 12 (AD: 8/27, CRC: 11/51 (0.216)) and 13 (CRC: 3/51 (0.06)) were the most frequent in our sample set, with G12V (5/27) dominance in ADs and G12D (5/51 (0.098)) in CRCs. In terms of the cfDNA WES results, tumor somatic variants were found in 6/33 of CRC cases. Panel sequencing revealed somatic variants in 8 out of the 12 enrolled patients, identifying 12/20 tumor somatic variants falling on its targeted regions, while WES recovered only 20% in the respective regions in cfDNA of the same patients. In liquid biopsy analyses, WES is less efficient compared to the targeted panel sequencing with a higher coverage depth that can hold a relevant clinical potential to be applied in everyday practice in the future. Full article
(This article belongs to the Special Issue Liquid Biopsy in Gastrointestinal Cancers)
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13 pages, 1867 KiB  
Article
Circulating Tumor DNA-Based Disease Monitoring of Patients with Locally Advanced Esophageal Cancer
by Lisa S. M. Hofste, Maartje J. Geerlings, Daniel von Rhein, Sofie H. Tolmeijer, Marjan M. Weiss, Christian Gilissen, Tom Hofste, Linda M. Garms, Marcel J. R. Janssen, Heidi Rütten, Camiel Rosman, Rachel S. van der Post, Bastiaan R. Klarenbeek and Marjolijn J. L. Ligtenberg
Cancers 2022, 14(18), 4417; https://doi.org/10.3390/cancers14184417 - 11 Sep 2022
Cited by 10 | Viewed by 2124
Abstract
Patients diagnosed with locally advanced esophageal cancer are often treated with neoadjuvant chemoradiotherapy followed by surgery. This study explored whether detection of circulating tumor DNA (ctDNA) in plasma can be used to predict residual disease during treatment. Diagnostic tissue biopsies from patients with [...] Read more.
Patients diagnosed with locally advanced esophageal cancer are often treated with neoadjuvant chemoradiotherapy followed by surgery. This study explored whether detection of circulating tumor DNA (ctDNA) in plasma can be used to predict residual disease during treatment. Diagnostic tissue biopsies from patients with esophageal cancer receiving neoadjuvant chemoradiotherapy and surgery were analyzed for tumor-specific mutations. These tumor-informed mutations were used to measure the presence of ctDNA in serially collected plasma samples using hybrid capture-based sequencing. Plasma samples were obtained before chemoradiotherapy, and prior to surgery. The association between ctDNA detection and progression-free and overall survival was measured. Before chemoradiotherapy, ctDNA was detected in 56% (44/78) of patients and detection was associated with tumor stage and volume (p = 0.05, Fisher exact and p = 0.02, Mann-Whitney, respectively). After chemoradiotherapy, ctDNA was detected in 10% (8/78) of patients. This preoperative detection of ctDNA was independently associated with recurrent disease (hazard ratio 2.8, 95% confidence interval 1.1–6.8, p = 0.03, multivariable Cox-regression) and worse overall survival (hazard ratio 2.9, 95% confidence interval 1.2–7.1, p = 0.02, multivariable Cox-regression).Ultradeep sequencing-based detection of ctDNA in preoperative plasma of patients with locally advanced esophageal cancer may help to assess which patients have a high risk of recurrence after neoadjuvant chemoradiotherapy and surgery. Full article
(This article belongs to the Special Issue Liquid Biopsy in Gastrointestinal Cancers)
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15 pages, 1504 KiB  
Article
Blood Circulating CD133+ Extracellular Vesicles Predict Clinical Outcomes in Patients with Metastatic Colorectal Cancer
by Davide Brocco, Pasquale Simeone, Davide Buca, Pietro Di Marino, Michele De Tursi, Antonino Grassadonia, Laura De Lellis, Maria Teresa Martino, Serena Veschi, Manuela Iezzi, Simone De Fabritiis, Marco Marchisio, Sebastiano Miscia, Alessandro Cama, Paola Lanuti and Nicola Tinari
Cancers 2022, 14(5), 1357; https://doi.org/10.3390/cancers14051357 - 07 Mar 2022
Cited by 15 | Viewed by 2669
Abstract
Colorectal cancer (CRC) is one of the most incident and lethal malignancies worldwide. Recent treatment advances prolonged survival in patients with metastatic colorectal cancer (mCRC). However, there are still few biomarkers to guide clinical management and treatment selection in mCRC. In this study, [...] Read more.
Colorectal cancer (CRC) is one of the most incident and lethal malignancies worldwide. Recent treatment advances prolonged survival in patients with metastatic colorectal cancer (mCRC). However, there are still few biomarkers to guide clinical management and treatment selection in mCRC. In this study, we applied an optimized flow cytometry protocol for EV identification, enumeration, and subtyping in blood samples of 54 patients with mCRC and 48 age and sex-matched healthy controls (HCs). The overall survival (OS) and overall response rate (ORR) were evaluated in mCRC patients enrolled and treated with a first line fluoropyrimidine-based regimen. Our findings show that patients with mCRC presented considerably higher blood concentrations of total EVs, as well as CD133+ and EPCAM+ EVs compared to HCs. Overall survival analysis revealed that increased blood concentrations of total EVs and CD133+ EVs before treatment were significantly associated with shorter OS in mCRC patients (p = 0.001; and p = 0.0001, respectively). In addition, we observed a correlation between high blood levels of CD133+ EVs at baseline and reduced ORR to first-line systemic therapy (p = 0.045). These findings may open exciting perspectives into the application of novel blood-based EV biomarkers for improved risk stratification and optimized treatment strategies in mCRC. Full article
(This article belongs to the Special Issue Liquid Biopsy in Gastrointestinal Cancers)
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Review

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20 pages, 984 KiB  
Review
Finding Waldo: The Evolving Paradigm of Circulating Tumor DNA (ctDNA)—Guided Minimal Residual Disease (MRD) Assessment in Colorectal Cancer (CRC)
by Sakti Chakrabarti, Anup Kumar Kasi, Aparna R. Parikh and Amit Mahipal
Cancers 2022, 14(13), 3078; https://doi.org/10.3390/cancers14133078 - 23 Jun 2022
Cited by 9 | Viewed by 3362
Abstract
Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent [...] Read more.
Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent colorectal surgery has remained an enduring challenge. The current risk stratification strategy relies on clinicopathologic characteristics of the tumors that lacks precision and results in over-and undertreatment in a significant proportion of patients. Consequently, a biomarker that can reliably identify patients harboring MRD would be of critical importance in refining patient selection for adjuvant therapy. Several prospective cohort studies have provided compelling data suggesting that ctDNA could be a robust biomarker for MRD that outperforms all existing clinicopathologic criteria. Numerous clinical trials are currently underway to validate the ctDNA-guided MRD assessment and adjuvant treatment strategies. Once validated, the ctDNA technology will likely transform the adjuvant therapy paradigm of colorectal cancer, supporting ctDNA-guided treatment escalation and de-escalation. The current article presents a comprehensive overview of the published studies supporting the utility of ctDNA for MRD assessment in patients with CRC. We also discuss ongoing ctDNA-guided adjuvant clinical trials that will likely shape future adjuvant therapy strategies for patients with CRC. Full article
(This article belongs to the Special Issue Liquid Biopsy in Gastrointestinal Cancers)
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