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New Biomarkers in Cancers (Volume II)
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New Biomarkers in Cancers (Volume II)

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

Deadline for manuscript submissions: 15 December 2024 | Viewed by 10229

Special Issue Editor

Prof. Dr. Jochen Sven Utikal

E-Mail Website
Guest Editor
1. Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany
2. Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany
Interests: skin cancer; malignant melanoma; translational research; stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This collection is the second edition of the previous one "New Biomarkers in Cancers" (https://www.mdpi.com/journal/cancers/special_issues/NBCancers).

In recent years, several new therapies have been approved for different cancer entities. Due to these new therapeutic options, physicians are confronted with new challenges, such as monitoring progression and stratifying patients for appropriate treatments.

Novel analytical techniques using body fluids, such as blood, and tumor tissue have identified numerous possible biomarkers.

In this Special Issue, we will publish reviews and original research that provide new insights into the role of predictive and prognostic tumor biomarkers. Novel insights into tumor biomarkers are particularly welcome.

Prof. Dr. Jochen Sven Utikal
Guest Editor

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

  • cancer
  • biomarker
  • molecule
  • serum
  • tumor
  • liquid biopsy
  • circulating tumor DNA
  • DNA
  • RNA
  • protein
  • circulating tumor cells
  • prognosis
  • prediction
  • indicator
  • traceable substance

Published Papers (7 papers)

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Research

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11 pages, 568 KiB  
Article
Type IX Collagen Turnover Is Altered in Patients with Solid Tumors
by Helena Port, Yi He, Morten A. Karsdal, Emilie A. Madsen, Anne-Christine Bay-Jensen, Nicholas Willumsen and Signe Holm Nielsen
Cancers 2024, 16(11), 2035; https://doi.org/10.3390/cancers16112035 - 27 May 2024
Viewed by 181
Abstract
The fibrotic tumor microenvironment, characterized by its intricate extracellular matrix (ECM), consists of many collagens with diverse functions and unexplored biomarker potential. Type IX collagen is a member of the low-abundance collagen family known as the fibril-associated collagen with interrupted triple helices (FACITs) [...] Read more.
The fibrotic tumor microenvironment, characterized by its intricate extracellular matrix (ECM), consists of many collagens with diverse functions and unexplored biomarker potential. Type IX collagen is a member of the low-abundance collagen family known as the fibril-associated collagen with interrupted triple helices (FACITs) and is found mostly in cartilage. Its role in the tumor microenvironment remains unexplored. To investigate the biomarker potential of a type IX collagen in cancer, an immuno-assay was developed (PRO-C9) and technical assay performance was evaluated for the assessment of serum. PRO-C9 levels were measured in serum samples from 259 patients with various solid tumor types compared to serum levels from 73 healthy controls. PRO-C9 levels were significantly elevated in patients with solid tumors including bladder, breast, colorectal, gastric, head and neck, lung, melanoma, ovarian, pancreatic, and renal compared to levels in healthy controls (p < 0.05–p < 0.0001). PRO-C9 could discriminate between patients with cancer and healthy controls, with the area under the receiver operating characteristic values ranging from 0.58 to 0.86 (p < 0.3–p < 0.0001), indicating potential diagnostic utility. This study suggests that type IX collagen turnover is altered in patients with solid tumors and demonstrates the feasibility of using PRO-C9 as a non-invasive serum-based biomarker with relevance in multiple cancer types. Furthermore, these results underscore the potential utility of PRO-C9 to better elucidate the biology of FACITs in cancers. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers (Volume II))
16 pages, 3216 KiB  
Article
Protein Arginine Methylation Patterns in Plasma Small Extracellular Vesicles Are Altered in Patients with Early-Stage Pancreatic Ductal Adenocarcinoma
by Kritisha Bhandari, Jeng Shi Kong, Katherine Morris, Chao Xu and Wei-Qun Ding
Cancers 2024, 16(3), 654; https://doi.org/10.3390/cancers16030654 - 3 Feb 2024
Cited by 1 | Viewed by 1079
Abstract
Small extracellular vesicles (sEVs) contain lipids, proteins and nucleic acids, which often resemble their cells of origin. Therefore, plasma sEVs are considered valuable resources for cancer biomarker development. However, previous efforts have been largely focused on the level of proteins and miRNAs in [...] Read more.
Small extracellular vesicles (sEVs) contain lipids, proteins and nucleic acids, which often resemble their cells of origin. Therefore, plasma sEVs are considered valuable resources for cancer biomarker development. However, previous efforts have been largely focused on the level of proteins and miRNAs in plasma sEVs, and the post-translational modifications of sEV proteins, such as arginine methylation, have not been explored. Protein arginine methylation, a relatively stable post-translational modification, is a newly described molecular feature of PDAC. The present study examined arginine methylation patterns in plasma sEVs derived from patients with early-stage PDAC (n = 23) and matched controls. By utilizing the arginine methylation-specific antibodies for western blotting, we found that protein arginine methylation patterns in plasma sEVs are altered in patients with early-stage PDAC. Specifically, we observed a reduction in the level of symmetric dimethyl arginine (SDMA) in plasma sEV proteins derived from patients with early- and late-stage PDAC. Importantly, immunoprecipitation followed by proteomics analysis identified a number of arginine-methylated proteins exclusively present in plasma sEVs derived from patients with early-stage PDAC. These results indicate that arginine methylation patterns in plasma sEVs are potential indicators of PDAC, a new concept meriting further investigation. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers (Volume II))
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12 pages, 1350 KiB  
Article
Biomarker Analysis from a Phase I/Ib Study of Regorafenib and Nivolumab in Mismatch Repair-Proficient Advanced Refractory Colorectal Cancer
by Dae Won Kim, Young-Chul Kim, Bence P. Kovari, Maria Martinez, Ruoyu Miao, James Yu, Rutika Mehta, Jonathan Strosberg, Iman Imanirad and Richard D. Kim
Cancers 2024, 16(3), 556; https://doi.org/10.3390/cancers16030556 - 28 Jan 2024
Viewed by 1193
Abstract
Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples [...] Read more.
Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples from the patients in the trial were collected and evaluated to discover potential biomarkers. The obtained samples were assessed for immunohistochemistry, ELISA and RNA sequencing. Their correlations with clinical outcome were analyzed. A high albumin level was significantly associated with improved progression-free survival (PFS), overall survival (OS) and disease control. Non-liver metastatic disease showed prolonged PFS and OS. Low regulatory T-cell (Treg) infiltration correlated with prolonged PFS. Low MIP-1β was associated with durable response and improved OS significantly. Upregulation of 23 genes, including CAPN9, NAPSA and ROS1, was observed in the durable disease control group, and upregulation of 10 genes, including MRPS18A, MAIP1 and CMTR2, was associated with a statistically significant improvement of PFS. This study suggests that pretreatment albumin, MIP-1β, non-liver metastatic disease and Treg infiltration may be potential predictive biomarkers of regorafenib/nivolumab in pMMR colorectal cancer. Further studies are needed to confirm these findings. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers (Volume II))
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21 pages, 1577 KiB  
Article
A Novel Gene List Identifies Tumors with a Stromal-Mesenchymal Phenotype and Worse Prognosis in Gastric Cancer
by Secil Demirkol Canli, Meral Uner, Baris Kucukkaraduman, Diren Arda Karaoglu, Aynur Isik, Nesrin Turhan, Aytekin Akyol, Ismail Gomceli and Ali Osmay Gure
Cancers 2023, 15(11), 3035; https://doi.org/10.3390/cancers15113035 - 2 Jun 2023
Viewed by 1651
Abstract
Background: Molecular biomarkers that predict disease progression can help identify tumor subtypes and shape treatment plans. In this study, we aimed to identify robust biomarkers of prognosis in gastric cancer based on transcriptomic data obtained from primary gastric tumors. Methods: Microarray, RNA sequencing, [...] Read more.
Background: Molecular biomarkers that predict disease progression can help identify tumor subtypes and shape treatment plans. In this study, we aimed to identify robust biomarkers of prognosis in gastric cancer based on transcriptomic data obtained from primary gastric tumors. Methods: Microarray, RNA sequencing, and single-cell RNA sequencing-based gene expression data from gastric tumors were obtained from public databases. Freshly frozen gastric tumors (n = 42) and matched FFPE (formalin-fixed, paraffin-embedded) (n = 40) tissues from a Turkish gastric cancer cohort were used for quantitative real-time PCR and immunohistochemistry-based assessments of gene expression, respectively. Results: A novel list of 20 prognostic genes was identified and used for the classification of gastric tumors into two major tumor subgroups with differential stromal gene expression (“Stromal-UP” (SU) and “Stromal-DOWN” (SD)). The SU group had a more mesenchymal profile with an enrichment of extracellular matrix-related gene sets and a poor prognosis compared to the SD group. Expression of the genes within the signature correlated with the expression of mesenchymal markers ex vivo. A higher stromal content in FFPE tissues was associated with shorter overall survival. Conclusions: A stroma-rich, mesenchymal subgroup among gastric tumors identifies an unfavorable clinical outcome in all cohorts tested. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers (Volume II))
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12 pages, 824 KiB  
Article
Selected Serum Biomarkers (Leptin, Chromogranin A, CA19-9, CEA) in Patients with Pancreatic Neuroendocrine Neoplasm and Associations with Metabolic Syndrome
by Violetta Rosiek, Agnes Bocian-Jastrzębska and Beata Kos-Kudła
Cancers 2023, 15(8), 2348; https://doi.org/10.3390/cancers15082348 - 18 Apr 2023
Viewed by 1370
Abstract
Metabolic abnormalities are well-known risk factors for many cancers, even though no clearly established link with pancreatic neuroendocrine neoplasms (PanNENs) has yet been investigated. This research aimed to assess the serum levels of leptin, chromogranin A (CgA), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic [...] Read more.
Metabolic abnormalities are well-known risk factors for many cancers, even though no clearly established link with pancreatic neuroendocrine neoplasms (PanNENs) has yet been investigated. This research aimed to assess the serum levels of leptin, chromogranin A (CgA), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) in patients with PanNENs and to search for associations between PanNENs, these selected serum biomarkers, and metabolic abnormalities in the form of metabolic syndrome (MS). Second, we aimed to investigate whether MS increases the risk of PanNENs. The serum concentrations of biomarkers, metabolic parameters (glucose, cholesterol, triglycerides), and anthropometric measurements (weight, height, BMI) were assessed in 106 patients with PanNENs and 40 healthy volunteers. Patients with PanNENs showed higher serum concentrations of CA19-9, CEA, and CgA in comparison to controls (p < 0.001, p = 0.042, and p = 0.025, respectively). Statistically significant differences in CEA levels were found in PanNENs patients with MS (p = 0.043). PanNENs patients with a BMI ≥ 25 kg/m2 and who were female exhibited significantly higher leptin levels (p < 0.001 and p = 0.013, respectively). Additionally, this study reflects the importance of determining markers. Future research should focus on understanding the impact of metabolic disturbances on PanNENs and accounting for the relationship between PanNENs and MS, such as other malignancies. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers (Volume II))
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18 pages, 1530 KiB  
Article
Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study
by Nikolaos Spathas, Anna C. Goussia, Georgia-Angeliki Koliou, Helen Gogas, Flora Zagouri, Anna Batistatou, Antonia V. Charchanti, Alexandra Papoudou-Bai, Mattheos Bobos, Sofia Chrisafi, Kyriakos Chatzopoulos, Ioannis Kostopoulos, Triantafyllia Koletsa, Petroula Arapantoni, Dimitrios Pectasides, Eleni Galani, Angelos Koutras, George Zarkavelis, Emmanouil Saloustros, Dimitrios Bafaloukos, Charisios Karanikiotis, Iliada Bompolaki, Gerasimos Aravantinos, Amanda Psyrri, Evangelia Razis, Anna Koumarianou, Eleni Res, Helena Linardou and George Fountzilasadd Show full author list remove Hide full author list
Cancers 2022, 14(22), 5635; https://doi.org/10.3390/cancers14225635 - 16 Nov 2022
Cited by 3 | Viewed by 1574
Abstract
Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and [...] Read more.
Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients’ tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers (Volume II))
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Review

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17 pages, 1266 KiB  
Review
The Antithetic Roles of IQGAP2 and IQGAP3 in Cancers
by Fei Song, Qingqing Dai, Marc-Oliver Grimm and Daniel Steinbach
Cancers 2023, 15(4), 1115; https://doi.org/10.3390/cancers15041115 - 9 Feb 2023
Cited by 7 | Viewed by 2134
Abstract
The scaffold protein family of IQ motif-containing GTPase-activating proteins (IQGAP1, 2, and 3) share a high degree of homology and comprise six functional domains. IQGAPs bind and regulate the cytoskeleton, interact with MAP kinases and calmodulin, and have GTPase-related activity, as well as [...] Read more.
The scaffold protein family of IQ motif-containing GTPase-activating proteins (IQGAP1, 2, and 3) share a high degree of homology and comprise six functional domains. IQGAPs bind and regulate the cytoskeleton, interact with MAP kinases and calmodulin, and have GTPase-related activity, as well as a RasGAP domain. Thus, IQGAPs regulate multiple cellular processes and pathways, affecting cell division, growth, cell–cell interactions, migration, and invasion. In the past decade, significant evidence on the function of IQGAPs in signal transduction during carcinogenesis has emerged. Compared with IQGAP1, IQGAP2 and IQGAP3 were less analyzed. In this review, we summarize the different signaling pathways affected by IQGAP2 and IQGAP3, and the antithetic roles of IQGAP2 and IQGAP3 in different types of cancer. IQGAP2 expression is reduced and plays a tumor suppressor role in most solid cancer types, while IQGAP3 is overexpressed and acts as an oncogene. In lymphoma, for example, IQGAPs have partially opposite functions. There is considerable evidence that IQGAPs regulate a multitude of pathways to modulate cancer processes and chemoresistance, but some questions, such as how they trigger this signaling, through which domains, and why they play opposite roles on the same pathways, are still unanswered. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers (Volume II))
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Bortezomib Pharmacogenetic Biomarkers for the Treatment of Multiple Myeloma: Review and Future Perspectives
Authors: Antonio Sanz-Solas; Jorge Labrador; Beatriz Cuevas; Raquel Alcaraz; Mª Victoria Cuevas; Francisco Javier Díaz-Gálvez; Raúl Azibeiro; Rodolfo Álvarez-Nuño; Gerardo Hermida; Pablo Zubiaur; Gina Mejía-Abril; Francisco Abad-Santos; Miriam Saiz-Rodríguez *
Affiliation: 1 Research Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, Burgos, Spain 2 Haematology Department, Hospital Universitario de Burgos, Burgos, Spain 3 Clinical Pharmacology Department, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.
Abstract: Multiple myeloma (MM) is a plasma cell malignancy that represents the second most common hematologic tumor. Bortezomib is the first proteasome inhibitor approved for use in patients with newly diagnosed or relapsed/refractory MM. Patients treated with bortezomib are at increased risk for thrombocytopenia, neutropenia, gastrointestinal toxicities, peripheral neuropathy, infection and fatigue. The response to bortezomib and the incidence of adverse drug reactions (ADRs) vary among patients, which could be due to interindividual variations in drug metabolizing enzymes and transporters. Our objective is to review the pharmacogenetic biomarkers described to date for their influence on the response and risk of ADRs to bortezomib. In turn, we will propose possible future strategies for the study and discovery of new biomarkers predictive of bortezomib toxicity. The identification of the factors that influence the efficacy and safety of bortezomib will lay the foundations for precision medicine, based on dose adjustments and the genetic profile of patients.

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