Cancers

Research

16 pages, 1773 KiB

Open AccessArticle

Molecular Divergence upon EGFR-TKI Resistance Could Be Dependent on the Exon Location of the Original EGFR-Sensitizing Mutation

by Roberto Serna-Blasco, Estela Sánchez-Herrero, Lucía Robado de Lope, Sandra Sanz-Moreno, Alejandro Rodríguez-Festa, Dunixe Ares-Trotta, Alberto Cruz-Bermúdez, Fabio Franco, Alfredo Sánchez-Hernández, María de Julián Campayo, Carlos García-Girón, Manuel Dómine, Ana Blasco, José M. Sánchez, Juana Oramas, Joaquim Bosch-Barrera, María Á. Sala, María Sereno, Atocha Romero and Mariano Provencio

Cancers 2022, 14(18), 4446; https://doi.org/10.3390/cancers14184446 - 13 Sep 2022

Viewed by 2402

Abstract

Tumor molecular profiling upon disease progression enables investigations of the tumor evolution. Next-generation sequencing (NGS) of liquid biopsies constitutes a noninvasive readily available source of tumor molecular information. In this study, 124 plasma samples from advanced EGFR-positive NSCLC patients, treated with a [...] Read more.

Tumor molecular profiling upon disease progression enables investigations of the tumor evolution. Next-generation sequencing (NGS) of liquid biopsies constitutes a noninvasive readily available source of tumor molecular information. In this study, 124 plasma samples from advanced EGFR-positive NSCLC patients, treated with a first-line EGFR tyrosine kinase inhibitor (EGFR-TKI) were collected upon disease progression. The circulating cell-free DNA (cfDNA) was sequenced using the Oncomine Pan-Cancer Cell-Free Assay™. Excluding EGFR mutations, the most frequently mutated gene was TP53 (57.3%), followed by APC (11.3%), FGFR3 (7.3%), and KRAS (5.6%). Different molecular alterations were observed upon disease progression depending on the location of the original EGFR-sensitizing mutation. Specifically, the detection of the p.T790M mutation was significantly associated with the presence of exon 19 mutations in EGFR (Fisher p-value: 0.028). All KRAS activating mutations (n = 8) were detected in tumors with EGFR mutations in exons 18 and 21 (Fisher p-value < 0.001). Similarly, mutations in NRAS and HRAS were more frequently detected in samples from tumors harboring mutations in exons 18 or 21 (Fisher p-value: 0.050 and Fisher p-value: 0.099, respectively). In conclusion, our data suggest that the mechanisms underlying EGFR-TKI resistance could be dependent on the exon location of the original EGFR-sensitizing mutation. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Figure 1

17 pages, 2177 KiB

Open AccessArticle

Assessment of a Size-Based Method for Enriching Circulating Tumour Cells in Colorectal Cancer

by Sai Shyam Vasantharajan, Edward Barnett, Elin S. Gray, John L. McCall, Euan J. Rodger, Michael R. Eccles, Fran Munro, Sharon Pattison and Aniruddha Chatterjee

Cancers 2022, 14(14), 3446; https://doi.org/10.3390/cancers14143446 - 15 Jul 2022

Cited by 4 | Viewed by 3033

Abstract

Circulating tumour cells (CTC) from solid tumours are a prerequisite for metastasis. Isolating CTCs and understanding their biology is essential for developing new clinical tests and precision oncology. Currently, CellSearch is the only FDA (U.S. Food and Drug Administration)-approved method for CTC enrichment [...] Read more.

Circulating tumour cells (CTC) from solid tumours are a prerequisite for metastasis. Isolating CTCs and understanding their biology is essential for developing new clinical tests and precision oncology. Currently, CellSearch is the only FDA (U.S. Food and Drug Administration)-approved method for CTC enrichment but possesses several drawbacks owing to a reliance on the epithelial cell adhesion molecule (EpCAM) and a resource-intensive nature. Addressing these shortcomings, we optimised an existing size-based method, MetaCell, to enrich CTCs from blood of colorectal cancer (CRC) patients. We evaluated the ability of MetaCell to enrich CTCs by spiking blood with CRC cell lines and assessing the cell recovery rates and WBC depletion via immunostaining and gene expression. We then applied MetaCell to samples from 17 CRC patients and seven controls. Recovery rates were >85% in cell lines, with >95% depletion in WBCs. MetaCell yielded CTCs and CTC clusters in 52.9% and 23.5% of the patients, respectively, without false positives in control patients. CTCs and cluster detection did not correlate with histopathological parameters. Overall, we demonstrated that the MetaCell platform enriched CRC cells with high recovery rates and high purity. Our pilot study also demonstrated the ability of MetaCell to detect CTCs in CRC patients. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Figure 1

16 pages, 2118 KiB

Open AccessArticle

Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy

by Sidsel C. Lindgaard, Emil Maag, Zsófia Sztupinszki, Inna M. Chen, Astrid Z. Johansen, Benny V. Jensen, Stig E. Bojesen, Dorte L. Nielsen, Zoltan Szallasi and Julia S. Johansen

Cancers 2022, 14(13), 3250; https://doi.org/10.3390/cancers14133250 - 1 Jul 2022

Cited by 7 | Viewed by 2450

Abstract

Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a dismal prognosis. We aimed to find a prognostic protein signature for overall survival (OS) in patients with advanced PDAC, and to explore whether early changes in circulating-protein levels could predict survival. We investigated 92 [...] Read more.

Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a dismal prognosis. We aimed to find a prognostic protein signature for overall survival (OS) in patients with advanced PDAC, and to explore whether early changes in circulating-protein levels could predict survival. We investigated 92 proteins using the Olink Immuno-Oncology panel in serum samples from 363 patients with advanced PDAC. Protein panels for several survival cut-offs were developed independently by two bioinformaticians using LASSO and Ridge regression models. Two panels of proteins discriminated patients with OS < 90 days from those with OS > 2 years. Index I (CSF-1, IL-6, PDCD1, TNFRSF12A, TRAIL, TWEAK, and CA19-9) had AUCs of 0.99 (95% CI: 0.98–1) (discovery cohort) and 0.89 (0.74–1) (replication cohort). For Index II (CXCL13, IL-6, PDCD1, and TNFRSF12A), the corresponding AUCs were 0.97 (0.93–1) and 0.82 (0.68–0.96). Four proteins (ANGPT2, IL-6, IL-10, and TNFRSF12A) were associated with survival across all treatment groups. Longitudinal samples revealed several changes, including four proteins that were also part of the prognostic signatures (CSF-1, CXCL13, IL-6, TNFRSF12A). This study identified two circulating-protein indices with the potential to identify patients with advanced PDAC with very short OS and with long OS. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Figure 1

11 pages, 1617 KiB

Open AccessArticle

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control

by Douglas Guedes de Castro, Antônio Cássio Assis Pellizzon, Alexcia Camila Braun, Michael Jenwei Chen, Maria Letícia Gobo Silva, Ricardo Cesar Fogaroli, Guilherme Rocha Melo Gondim, Henderson Ramos, Elson Santos Neto, Carolina Humeres Abrahão, Liao Shin Yu, Emne Ali Abdallah, Vinicius Fernando Calsavara and Ludmilla Thomé Domingos Chinen

Cancers 2022, 14(13), 3101; https://doi.org/10.3390/cancers14133101 - 24 Jun 2022

Cited by 6 | Viewed by 2361

Abstract

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases [...] Read more.

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025–0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Figure 1

41 pages, 54324 KiB

Open AccessArticle

Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation

by Areeg M. Dabbish, Hana M. Abdelzaher, Moustafa Abohawya, Samir Shamma, Yosra H. Mahmoud, Amr Maged, Mohamed Manaa, Mohamed Hassany, Firas Kobeissy, Omid Bazgir, Hassan El-Fawal, Hassan M. E. Azzazy and Anwar Abdelnaser

Cancers 2022, 14(13), 3036; https://doi.org/10.3390/cancers14133036 - 21 Jun 2022

Cited by 8 | Viewed by 2310

Abstract

Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early [...] Read more.

Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using a bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE-miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424, and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV, and 72 HCV-associated-HCC patients using real-time PCR (qPCR). There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. A panel of five miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). These preliminary data show that the novel miRNAs panel (miR-150, miR-199a, miR-224, miR-424, and miR-3607) could serve as a potential non-invasive biomarker for HCC early prediction in chronic HCV patients. Further prospective studies on a larger cohort of patients should be conducted to assess the potential prognostic ability of the miRNAs panel. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Figure 1

14 pages, 7389 KiB

Open AccessArticle

Extracellular Vesicle-Based Method for Detecting MYCN Amplification Status of Pediatric Neuroblastoma

by Jirawan Panachan, Napat Rojsirikulchai, Nutkridta Pongsakul, Ladawan Khowawisetsut, Pongpak Pongphitcha, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul, Pitichai Phornsarayuth, Nisakorn Klinkulab, Natini Jinawath, Wararat Chiangjong, Usanarat Anurathapan, Kovit Pattanapanyasat, Suradej Hongeng and Somchai Chutipongtanate

Cancers 2022, 14(11), 2627; https://doi.org/10.3390/cancers14112627 - 26 May 2022

Cited by 14 | Viewed by 3036

Abstract

MYCN amplification is the strongest predictor of high-risk neuroblastoma (NB). The standard procedure to detect MYCN status requires invasive procedures. Extracellular vesicles (EVs) contain molecular signatures of originated cells, present in biofluids, and serve as an invaluable source for cancer liquid biopsies. This [...] Read more.

MYCN amplification is the strongest predictor of high-risk neuroblastoma (NB). The standard procedure to detect MYCN status requires invasive procedures. Extracellular vesicles (EVs) contain molecular signatures of originated cells, present in biofluids, and serve as an invaluable source for cancer liquid biopsies. This study aimed to establish an EV-based method to detect the MYCN status of NB. Two EV subtypes, i.e., microvesicles (MVs) and exosomes, were sequentially isolated from the culture supernatant by step-wise centrifugation, ultrafiltration, and size-exclusion chromatography. Quantitative RT-PCR was performed to detect MYCN mRNA. As a result, MYCN mRNA was detectable in the MVs, but not exosomes, of MYCN-amplified NB cells. MYCN mRNA-containing MVs (MYCN-MV) were successfully detected in three distinct MYCN-amplified NB cell lines but absent in three MYCN non-amplification cells. The simulated samples were prepared by pulsing MVs into human serum. MYCN–MV detection in the simulated samples showed a less interfering effect from the human blood matrix. Validation using clinical specimens (2 mL bone marrow plasma) obtained from patients at various disease stages showed a promising result. Five out of six specimens of MYCN-amplified patients showed positive results, while there were no false positives in four plasma samples of the MYCN non-amplification group. This study communicated a novel EV-based method for detecting the MYCN status of pediatric NB based on MYCN mRNA contents in MVs. Future studies should be pursued in a prospective cohort to determine its true diagnostic performance. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Graphical abstract

12 pages, 671 KiB

Open AccessArticle

Semaphorin-3F/Neuropilin-2 Transcriptional Expression as a Predictive Biomarker of Occult Lymph Node Metastases in HNSCC

by Carla Meler-Claramonte, Francesc Xavier Avilés-Jurado, Isabel Vilaseca, Ximena Terra, Paloma Bragado, Gemma Fuster, Xavier León Vintró and Mercedes Camacho

Cancers 2022, 14(9), 2259; https://doi.org/10.3390/cancers14092259 - 30 Apr 2022

Cited by 6 | Viewed by 2105

Abstract

The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head [...] Read more.

The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head and neck squamous cell carcinomas. We analyzed the transcriptional expression of SEMA3F and NRP2 in a cohort of 53 patients with cN0 squamous cell carcinoma treated with an elective neck dissection. Occult lymph node metastases were found in 37.7% of the patients. Patients with occult lymph node metastases (cN0/pN+) had significantly lower SEMA3F expression values than patients without lymph node involvement (cN0/pN0). Considering the expression of the SEMA3F-NRP2 genes, patients were classified into two groups according to the risk of occult nodal metastasis: Group 1 (n = 34), high SEMA3F/low NRP2 expression, with a low risk of occult nodal involvement (14.7% cN0/pN+); Group 2 (n = 19), low SEMA3F or high SEMA3F/high NRP2 expression, with a high risk of occult nodal involvement (78.9% cN0/pN+). Multivariate analysis showed that patients in Group 2 had a 26.2 higher risk of lymph node involvement than patients in Group 1. There was a significant relationship between the transcriptional expression values of the SEMA3F-NRP2 genes and the risk of occult nodal metastases. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Figure 1

10 pages, 1135 KiB

Open AccessArticle

Circulating Let-7 Family Members as Non-Invasive Biomarkers for Predicting Hepatocellular Carcinoma Risk after Antiviral Treatment among Chronic Hepatitis C Patients

by Yi-Shan Tsai, Ching-I Huang, Pei-Chien Tsai, Ming-Lun Yeh, Chung-Feng Huang, Meng-Hsuan Hsieh, Ta-Wei Liu, Yi-Hung Lin, Po-Cheng Liang, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai and Ming-Lung Yu

Cancers 2022, 14(8), 2023; https://doi.org/10.3390/cancers14082023 - 16 Apr 2022

Cited by 6 | Viewed by 2491

Abstract

HCC, a leading cause of cancer-related mortality, is diagnosed at advanced stages. Although antiviral therapy has reduced the risk of HCC among chronic hepatitis C (CHC) patients, the risk of HCC remains, thus, highlighting the unmet need for continuous surveillance. Therefore, stable and [...] Read more.

HCC, a leading cause of cancer-related mortality, is diagnosed at advanced stages. Although antiviral therapy has reduced the risk of HCC among chronic hepatitis C (CHC) patients, the risk of HCC remains, thus, highlighting the unmet need for continuous surveillance. Therefore, stable and cost-effective biomarkers, such as circulating microRNAs, must be identified. We aimed to clarify whether serum levels of the Let-7 family can predict HCC risk in patients with CHC using univariate and multivariate Cox’s proportional hazards model. We analyzed the sera of 54 patients with CHC who developed HCC after antiviral therapy and compared the data with those of 173 patients without HCC development. The Let-7 family (except for let-7c) exhibited significant negative correlations with the fibrosis score (r = −0.2736 to −0.34, p = 0.0002 to <0.0001). After Cox’s regression model was used to adjust for age, sex, HCV genotype, and FIB-4 ≥ 3.25, patients with CHC with let-7i median ≥ −1.696 (adjusted hazard ratio [aHR] = 0.31, 95% CI: 0.08–0.94, p = 0.0372) in the sustained virologic response (SVR) groups and ≥−1.696 (aHR = 0.09, 95% CI: 0.08–0.94, p = 0.0022) in the non-SVR group were less likely to develop HCC. Thus, circulating let-7i can be used for early CHC surveillance in patients with HCC risk after antiviral treatment. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Figure 1

12 pages, 1482 KiB

Open AccessArticle

Prognostic Impact of Circulating Methylated Homeobox A9 DNA in Patients Undergoing Treatment for Recurrent Ovarian Cancer

by Louise Faaborg, Rikke Fredslund Andersen, Marianne Waldstrøm, Jon Røikjær Henriksen, Parvin Adimi, Anders Jakobsen and Karina Dahl Steffensen

Cancers 2022, 14(7), 1766; https://doi.org/10.3390/cancers14071766 - 30 Mar 2022

Cited by 9 | Viewed by 1663

Abstract

Methylated Homeobox A9 circulating tumor DNA (meth-HOXA9) has been suggested as a blood-based biomarker in epithelial ovarian cancer (EOC), although its prognostic significance remains unproven. The aim of the present study was to investigate the prognostic impact of meth-HOXA9 in [...] Read more.

Methylated Homeobox A9 circulating tumor DNA (meth-HOXA9) has been suggested as a blood-based biomarker in epithelial ovarian cancer (EOC), although its prognostic significance remains unproven. The aim of the present study was to investigate the prognostic impact of meth-HOXA9 in patients with recurrent EOC. DNA was purified from 4 mL plasma and, following bilsulfite conversion, meth-HOXA9 was analyzed using a methylation-specific droplet digital PCR. Detection of meth-HOXA9 was reported as a percentage of total DNA and as a binary variable (detectable and undetectable). Meth-HOXA9 status and its dynamics during palliative treatment were correlated with overall survival (OS) as the primary endpoint. At baseline, meth-HOXA9 was detected in 65.9% (83/126) of the patients. The median OS was 8.9 and 17.9 months in patients with detectable and undetectable meth-HOXA9 at baseline (hazard ratio: 2.04, p = 0.002), which remained significant in the multivariate analysis. Median OS in patients with an increase in meth-HOXA9 after one treatment cycle was 5.3 months compared to 33 months in patients with undetectable meth-HOXA9 (p < 0.001). Meth-HOXA9 was significantly related to poor survival and may serve as a prognostic marker in patients with recurrent EOC. The longitudinal monitoring of meth-HOXA9 is clinically feasible with the perspective of aiding clinical decision making. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Figure 1

26 pages, 2511 KiB

Open AccessArticle

Circulating Proteins Associated with Response and Resistance to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer

by María del Pilar Chantada-Vázquez, Mercedes Conde-Amboage, Lucía Graña-López, Sergio Vázquez-Estévez, Susana B. Bravo and Cristina Núñez

Cancers 2022, 14(4), 1087; https://doi.org/10.3390/cancers14041087 - 21 Feb 2022

Cited by 8 | Viewed by 3211

Abstract

Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more [...] Read more.

Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more for their ability to predict therapy response and aid in the development of personalized treatment regimens. This study aims to identify effective protein networks and biomarkers to predict response to NAC in HER2-positive BC patients through an exhaustive large-scale LC-MS/MS-based qualitative and quantitative proteomic profiling of serum samples from responders and non-responders. Serum samples from HER2-positive BC patients were collected before NAC and were processed by three methods (with and without nanoparticles). The qualitative analysis revealed differences in the proteomic profiles between responders and non-responders, mainly in proteins implicated in the complement and coagulation cascades and apolipoproteins. Qualitative analysis confirmed that three proteins (AFM, SERPINA1, APOD) were correlated with NAC resistance. In this study, we show that serum biomarker profiles can predict treatment response and outcome in the neoadjuvant setting. If these findings are further developed, they will be of significant clinical utility in the design of treatment regimens for individual BC patients. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Graphical abstract

15 pages, 1171 KiB

Open AccessArticle

Circulating Tumor Cell Kinetics and Morphology from the Liquid Biopsy Predict Disease Progression in Patients with Metastatic Colorectal Cancer Following Resection

by Drahomír Kolenčík, Sachin Narayan, Jana-Aletta Thiele, Dillon McKinley, Anna Sandström Gerdtsson, Lisa Welter, Petr Hošek, Pavel Ostašov, Ondřej Vyčítal, Jan Brůha, Ondřej Fiala, Ondřej Šorejs, Václav Liška, Pavel Pitule, Peter Kuhn and Stephanie N. Shishido

Cancers 2022, 14(3), 642; https://doi.org/10.3390/cancers14030642 - 27 Jan 2022

Cited by 5 | Viewed by 3886

Abstract

The liquid biopsy has the potential to improve current clinical practice in oncology by providing real-time personalized information about a patient’s disease status and response to treatment. In this study, we evaluated 161 peripheral blood (PB) samples that were collected around surgical resection [...] Read more.

The liquid biopsy has the potential to improve current clinical practice in oncology by providing real-time personalized information about a patient’s disease status and response to treatment. In this study, we evaluated 161 peripheral blood (PB) samples that were collected around surgical resection from 47 metastatic colorectal cancer (mCRC) patients using the High-Definition Single Cell Assay (HDSCA) workflow. In conjunction with the standard circulating tumor cell (CTC) enumeration, cellular morphology and kinetics between time-points of collection were considered in the survival analysis. CTCs, CTC-Apoptotic, and CTC clusters were found to indicate poor survival with an increase in cell count from pre-resection to post-resection. This study demonstrates that CTC subcategorization based on morphological differences leads to nuanced results between the subtypes, emphasizing the heterogeneity within the CTC classification. Furthermore, we show that factoring in the time-point of each blood collection is critical, both for its static enumeration and for the change in cell populations between draws. By integrating morphology and time-based analysis alongside standard CTC enumeration, liquid biopsy platforms can provide greater insight into the pathophysiology of mCRC by highlighting the complexity of the disease across a patient’s treatment. Full article

(This article belongs to the Special Issue Circulating Biomarkers in Cancer)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Circulating Biomarkers in Cancer

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (11 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI