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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 8712

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Special Issue Editor

Dr. Godfrey Grech

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Guest Editor

Department of Pathology, University of Malta, Msida, Malta
Interests: breast cancer biomarkers; tumour metastasis; tumour invasion markers; liquid biopsies

Special Issue Information

Dear Colleagues,

The aims of the Special Issue is to have a collection of well structured reviews and original articles to address the current knowledge and translation of breast cancer biomarkers into the clinic. Tumour heterogeneity, early detection of tumour invasion and tumour development, and the era of liquid biopsies are exciting, although they provide uncertainty and difficulties in translating novel biomarkers into the clinic. Hence the collection of well validated biomarkers used to measure the dynamic state of tumour progression in terms of early metastatic disease and invasion, circulating tumour cells and other components of tumour in blood is needed to shed light on the potential biomarkers to predict, classify and manage tumours with solid evidence-based knowledge. To date, predictive biomarkers for subtype triple negative breast cancer are still struggling to be implemented and translated into the clinic. In addition, the use of targeted therapies and therapeutic resistance requires novel emerging technologies to understand and address. Hence, we propose a Special Issue to collect evidence-based information and propose expert recommendations to overcome the current difficulties due to tumour development dynamics and heterogeneity. In addition, using technologies to address the required sensitivity to measure breast cancer characteristics in liquid biopsies for patient management and enhanced tumour diagnostics shall be addressed.

Dr. Godfrey Grech
Guest Editor

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Keywords

predictive biomarkers
tumour invasion
tumour heterogeneity
liquid biopsies

Published Papers (5 papers)

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Research

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15 pages, 2630 KiB

Open AccessArticle

Expression of the Immunohistochemical Markers CK5, CD117, and EGFR in Molecular Subtypes of Breast Cancer Correlated with Prognosis

by Carla E. Schulmeyer, Peter A. Fasching, Lothar Häberle, Julia Meyer, Michael Schneider, David Wachter, Matthias Ruebner, Patrik Pöschke, Matthias W. Beckmann, Arndt Hartmann, Ramona Erber and Paul Gass

Diagnostics 2023, 13(3), 372; https://doi.org/10.3390/diagnostics13030372 - 19 Jan 2023

Cited by 4 | Viewed by 1996

Abstract

Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS. Full article

(This article belongs to the Special Issue Breast Cancer Biomarkers)

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16 pages, 4654 KiB

Open AccessArticle

The Analysis of Relevant Gene Networks Based on Driver Genes in Breast Cancer

by Luxuan Qu, Zhiqiong Wang, Hao Zhang, Zhongyang Wang, Caigang Liu, Wei Qian and Junchang Xin

Diagnostics 2022, 12(11), 2882; https://doi.org/10.3390/diagnostics12112882 - 21 Nov 2022

Cited by 2 | Viewed by 1355

Abstract

Background: The occurrence and development of breast cancer has a strong correlation with a person’s genetics. Therefore, it is important to analyze the genetic factors of breast cancer for future development of potential targeted therapies from the genetic level. Methods: In this study, we complete an analysis of the relevant protein–protein interaction network relating to breast cancer. This includes three steps, which are breast cancer-relevant genes selection using mutual information method, protein–protein interaction network reconstruction based on the STRING database, and vital genes calculating by nodes centrality analysis. Results: The 230 breast cancer-relevant genes were chosen in gene selection to reconstruct the protein–protein interaction network and some vital genes were calculated by node centrality analyses. Node centrality analyses conducted with the top 10 and top 20 values of each metric found 19 and 39 statistically vital genes, respectively. In order to prove the biological significance of these vital genes, we carried out the survival analysis and DNA methylation analysis, inquired about the prognosis in other cancer tissues and the RNA expression level in breast cancer. The results all proved the validity of the selected genes. Conclusions: These genes could provide a valuable reference in clinical treatment among breast cancer patients. Full article

(This article belongs to the Special Issue Breast Cancer Biomarkers)

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11 pages, 1043 KiB

Open AccessArticle

Prognostic Value of Tumour-Infiltrating Lymphocytes in an Unselected Cohort of Breast Cancer Patients

by Kathleen Schüler, Daniel Bethmann, Sandy Kaufhold, Carolin Hartung, Kathrin Stückrath, Tilmann Lantzsch, Christoph Uleer, Volker Hanf, Susanne Peschel, Jutta John, Marleen Pöhler, Jörg Buchmann, Karl-Friedrich Bürrig, Edith Weigert, Christoph Thomssen, Eva Johanna Kantelhardt and Martina Vetter

Diagnostics 2022, 12(10), 2527; https://doi.org/10.3390/diagnostics12102527 - 18 Oct 2022

Cited by 3 | Viewed by 1281

Abstract

Tumour-infiltrating lymphocytes (TILs) are considered to have prognostic and predictive value for patients with early breast cancer. We examined 1166 breast cancer patients from a prospective, multicentre cohort (Prognostic Assessment in Routine Application (PiA), n = 1270, NCT 01592825) following recommendations from the International TILs Working Group. TIL quantification was performed using predefined groups and as a continuous variable in 10% increments. The primary objective was the distribution of TILs in different breast cancer types. The second objective was the association with the recurrence-free interval (RFI) and overall survival (OS). Stromal infiltration with more than 60% TILs appeared in 2% of hormone receptor (HR)-positive and HER2-negative tumours, in 9.8% of HER2-positive tumours (any HR) and 19.4% of triple-negative breast cancers (TNBCs). Each 10% increment was associated with an improvement in the prognosis in HER2-positive samples (RFI, hazard ratio 0.773, 95% CI 0.587–1.017; OS, hazard ratio 0.700, 95% CI 0.523–0.937). When defining exploratory cut-offs for TILs, the use of a 30% threshold for the HR-positive and HER2-negative group, a 20% threshold for the HER2 group and a 60% threshold for the TNBC group appeared to be the most suitable. TILs bore prognostic value, especially in HER2-positive breast cancer. For clinical use, additional research on the components of immune infiltration might be reasonable. Full article

(This article belongs to the Special Issue Breast Cancer Biomarkers)

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12 pages, 3026 KiB

Open AccessArticle

Bioinformatics Analysis of the Prognostic Significance of CAND1 in ERα-Positive Breast Cancer

by Rashed Alhammad

Diagnostics 2022, 12(10), 2327; https://doi.org/10.3390/diagnostics12102327 - 27 Sep 2022

Cited by 1 | Viewed by 1461

Abstract

The identification of novel prognostic biomarkers for breast cancer is an unmet clinical need. Cullin-associated and neddylation-dissociated 1 (CAND1) has been implicated in mediating carcinogenesis in prostate and lung cancers. In addition, CAND1 is an established prognostic biomarker for worse prognosis in liver cancer. However, the prognostic significance of CAND1 in breast cancer has not yet been explored. In this study, Breast Cancer Gene-Expression Miner (Bc-GenExMiner) and TIMER2.0 were utilized to explore the mRNA expression of CAND1 in ERα-positive breast cancer patients. The Kaplan–Meier plotter was used to explore the relationship between CAND1 expression and several prognostic indicators. The Gene Set Cancer Analysis (GSCA) web server was then used to explore the pathways of the genes that correlate with CAND1 in ERα-positive breast cancer. Immune infiltration was investigated using Bc-GenExMiner. Our bioinformatics analysis illustrates that breast cancer patients have higher CAND1 compared to normal breast tissue and that ERα-positive breast cancer patients with a high expression of CAND1 have poor overall survival (OS), distant metastasis-free survival (DMFS), and relapse-free survival (RFS) outcomes. Higher CAND1 expression was observed in histologic grade 3 compared to grades 2 and 1. Our results revealed that CAND1 positively correlates with lymph nodes and negatively correlates with the infiltration of immune cells, which is in agreement with published reports. Our findings suggest that CAND1 might mediate invasion and metastasis in ERα-positive breast cancer, possibly through the activation of estrogen and androgen signaling pathways; however, experiments should be carried out to further explore the role of CAND1 in activating the androgen and estrogen signaling pathways. In conclusion, the results suggest that CAND1 could be used as a potential novel biomarker for worse prognosis in ERα-positive breast cancer. Full article

(This article belongs to the Special Issue Breast Cancer Biomarkers)

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Review

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14 pages, 618 KiB

Open AccessReview

Liquid Biopsy in the Management of Breast Cancer Patients: Where Are We Now and Where Are We Going

by Carlotta Mazzitelli, Donatella Santini, Angelo Gianluca Corradini, Claudio Zamagni, Davide Trerè, Lorenzo Montanaro and Mario Taffurelli

Diagnostics 2023, 13(7), 1241; https://doi.org/10.3390/diagnostics13071241 - 25 Mar 2023

Cited by 4 | Viewed by 1978

Abstract

Liquid biopsy (LB) is an emerging diagnostic tool that analyzes biomarkers in the blood (and possibly in other body fluids) to provide information about tumor genetics and response to therapy. This review article provides an overview of LB applications in human cancer with a focus on breast cancer patients. LB methods include circulating tumor cells and cell-free tumor products, such as circulating tumor DNA. LB has shown potential in detecting cancer at an early stage, monitoring tumor progression and recurrence, and predicting patient response to therapy. Several studies have demonstrated its clinical utility in breast cancer patients. However, there are limitations to LB, including the lack of standardized assays and the need for further validation. Future potential applications of LB include identifying the minimal residual disease, early detection of recurrence, and monitoring treatment response in various cancer types. LB represents a promising non-invasive diagnostic tool with potential applications in breast cancer diagnosis, treatment, and management. Further research is necessary to fully understand its clinical utility and overcome its current limitations. Full article

(This article belongs to the Special Issue Breast Cancer Biomarkers)

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