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Cancer Biomarker: Current Status and Future Perspectives
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Cancer Biomarker: Current Status and Future Perspectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (15 September 2024) | Viewed by 15492

Special Issue Editors

Dr. Susan Costantini

E-Mail Website
Guest Editor
Experimental Pharmacology, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, 80131 Naples, Italy
Interests: cancer; cytokines; metabolome; NMR; systems biology; computational biology; molecular biology
Special Issues, Collections and Topics in MDPI journals
Dr. Francesca Capone

E-Mail Website
Guest Editor
Experimental Pharmacology, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, 80131 Naples, Italy
Interests: cancer biomarker

Special Issue Information

Dear Colleagues,

In recent years, omics technologies have led to the identification of numerous biomarkers based on DNA, RNA, miRNA, long non-coding RNA, protein, and metabolic and lipidic alterations that may be combined with clinical pathological data to greatly predict cancer progression, patient outcome, cancer recurrence, and therapeutic treatment responses.

To date, only a few cancer biomarkers have entered into clinical practice. However, the search for new prognostic and predictive biomarkers is the object of many studies performed on cells, blood samples, and tissues. In this context, so-called “liquid biopsies” allow a snapshot of a patient’s pathophysiological state at a given time and provide dynamic monitoring with insight into the spatial and temporal clonal evolution processes of the tumor, including secondary resistance to treatment, which is prohibited by the invasiveness of tissue biopsies.

The aim of this Special Issue is to present the latest research on the identification of new genetic, epigenetic, miRNA, protein, metabolic, and lipidic cancer biomarkers, and their combination and integration by bioinformatics and systems biology approaches.

Dr. Susan Costantini
Dr. Francesca Capone
Guest Editors

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Keywords

  • cancer
  • cytokines/chemokines
  • proteins
  • miRNAs
  • metabolites
  • lipids
  • extracellular vesicles
  • cell biology/tissue
  • liquid biopsy
  • systems biology

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Published Papers (6 papers)

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Research

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10 pages, 860 KiB  
Article
Assessing Urinary Para-Hydroxyphenylacetic Acid as a Biomarker Candidate in Neuroendocrine Neoplasms
by Renato de Falco, Susan Costantini, Luigi Russo, Denise Giannascoli, Anita Minopoli, Ottavia Clemente, Salvatore Tafuto, Carlo Vitagliano, Elena Di Gennaro, Alfredo Budillon and Ernesta Cavalcanti
Int. J. Mol. Sci. 2024, 25(22), 12317; https://doi.org/10.3390/ijms252212317 - 16 Nov 2024
Viewed by 460
Abstract
The management of neuroendocrine neoplasms (NENs) involves the measurement of serum chromogranin A (s-CGA), serum neuro-specific enolase (s-NSE), and urinary 5-hydroxindolacetic acid (5-HIAA). Urinary para-hydroxyphenylacetic acid (u-pHPAA), a metabolite of tyrosine, has been proposed as a potential biomarker for these diseases. This study [...] Read more.
The management of neuroendocrine neoplasms (NENs) involves the measurement of serum chromogranin A (s-CGA), serum neuro-specific enolase (s-NSE), and urinary 5-hydroxindolacetic acid (5-HIAA). Urinary para-hydroxyphenylacetic acid (u-pHPAA), a metabolite of tyrosine, has been proposed as a potential biomarker for these diseases. This study aims to evaluate the effectiveness of u-pHPAA and tyrosine as biomarkers. We measured the levels of s-CgA, s-NSE, u-5-HIAA, u-pHPAA, and tyrosine in blood or 24 h urine samples collected at baseline (T0) and after 1 year of follow-up (T1) from a limited cohort of patients enrolled at Istituto Nazionale Tumori-IRCCS-Fondazione “G. Pascale”. Biomarker values were normalized using the ratios between T1 and T0 values (T1/T0 parameters). The T1/T0 ratios for s-CgA and u-pHPAA were significantly associated with the outcome of death (p = 0.044 and p = 0.022, respectively). An ROC curve analysis demonstrated outstanding performances for these biomarkers (AUC = 0.958 and AUC = 1.00, respectively) and the Kaplan–Meier survival analysis showed significant Log-rank test results (p = 0.001 and p < 0.001, respectively). Additionally, T0 serum tyrosine correlated with the outcome of death (p = 0.044), with the ROC curve showing good performance (AUC = 0.958) and the Kaplan–Meier analysis yielding significant Log-rank test results (p = 0.007). Our study confirms the role of s-CgA in the management of NEN patients and highlights the potential roles of u-pHPAA and serum tyrosine as biomarkers. Further research is needed to validate our findings in larger populations. Full article
(This article belongs to the Special Issue Cancer Biomarker: Current Status and Future Perspectives)
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13 pages, 1417 KiB  
Article
Prognostic Significance of PD-L1 Expression on Circulating Myeloid-Derived Suppressor Cells in NSCLC Patients Treated with Anti-PD-1/PD-L1 Checkpoint Inhibitors
by Roser Salvia, Laura G. Rico, Teresa Morán, Jolene A. Bradford, Michael D. Ward, Ana Drozdowskyj, Joan Climent-Martí, Eva M. Martínez-Cáceres, Rafael Rosell and Jordi Petriz
Int. J. Mol. Sci. 2024, 25(22), 12269; https://doi.org/10.3390/ijms252212269 - 15 Nov 2024
Viewed by 306
Abstract
Even though anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) have improved survival, a high percentage of patients still do not respond to ICIs. Myeloid-derived suppressor cells (MDSCs) are circulating cells that express PD-L1 and can infiltrate and proliferate in [...] Read more.
Even though anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) have improved survival, a high percentage of patients still do not respond to ICIs. Myeloid-derived suppressor cells (MDSCs) are circulating cells that express PD-L1 and can infiltrate and proliferate in the tumor microenvironment, inducing immunosuppression. By evaluating changes in PD-L1 expression of live peripheral blood MDSCs, we are able to define a new PD-L1 index, useful in predicting ICI escape in NSCLC patients before initiating anti-PD-1/PD-L1 immunotherapy. In this study, a cohort of 37 NSCLC patients was prospectively analyzed, obtaining independent PD-L1 indexes. In patients with a PD-L1 index > 5.88, progressive disease occurred in 58.33% of patients [median progression-free survival (PFS) = 5.73 months; 95%CI = 2.67–20.53], showing significant differences when compared with patients with a PD-L1 index ≤ 5.88, in whom 7.69% progressed and median PFS was not reached (NR); p-value = 0.0042. Overall survival (OS) was significantly worse in patients with a high vs. low PD-L1 index (41.67% vs. 76.92%; median OS = 18.03 months, 95%CI = 6.77–25.23 vs. NR, 95%CI = 1.87-NR; p-value = 0.035). The PD-L1 index can be applied to stratify NSCLC patients according to their probability of response to ICIs at baseline. In addition to quantifying tumoral expression, this index could be used to compare nonresponse to treatment. Full article
(This article belongs to the Special Issue Cancer Biomarker: Current Status and Future Perspectives)
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16 pages, 2053 KiB  
Article
Quantitative Proteomic Analysis of MCM3 in ThinPrep Samples of Patients with Cervical Preinvasive Cancer
by Büşra Köse, Ralf van de Laar, Heleen van Beekhuizen, Folkert van Kemenade, Ahmet Tarik Baykal, Theo Luider and Coşkun Güzel
Int. J. Mol. Sci. 2023, 24(13), 10473; https://doi.org/10.3390/ijms241310473 - 21 Jun 2023
Cited by 2 | Viewed by 2117
Abstract
Triage methods for cervical cancer detection show moderate accuracy and present considerable false-negative and false-positive result rates. A complementary diagnostic parameter could help improve the accuracy of identifying patients who need treatment. A pilot study was performed using a targeted proteomics approach with [...] Read more.
Triage methods for cervical cancer detection show moderate accuracy and present considerable false-negative and false-positive result rates. A complementary diagnostic parameter could help improve the accuracy of identifying patients who need treatment. A pilot study was performed using a targeted proteomics approach with opportunistic ThinPrep samples obtained from women collected at the hospital’s outpatient clinic to determine the concentration levels of minichromosome maintenance-3 (MCM3) and envoplakin (EVPL) proteins. Forty samples with ‘negative for intraepithelial lesion or malignancy’ (NILM), 21 samples with ‘atypical squamous cells of undetermined significance’ (ASC-US), and 33 samples with ‘low-grade squamous intraepithelial lesion and worse’ (≥LSIL) were analyzed, using cytology and the patients’ histology reports. Highly accurate concordance was obtained for gold-standard-confirmed samples, demonstrating that the MCM3/EVPL ratio can discriminate between non-dysplastic and dysplastic samples. On that account, we propose that MCM3 and EVPL are promising candidate protein biomarkers for population-based cervical cancer screening. Full article
(This article belongs to the Special Issue Cancer Biomarker: Current Status and Future Perspectives)
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Review

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29 pages, 3195 KiB  
Review
Non-Genomic Hallmarks of Aging—The Review
by Drahomira Holmannova, Pavel Borsky, Helena Parova, Tereza Stverakova, Milan Vosmik, Libor Hruska, Zdenek Fiala and Lenka Borska
Int. J. Mol. Sci. 2023, 24(20), 15468; https://doi.org/10.3390/ijms242015468 - 23 Oct 2023
Cited by 3 | Viewed by 3608
Abstract
Aging is a natural, gradual, and inevitable process associated with a series of changes at the molecular, cellular, and tissue levels that can lead to an increased risk of many diseases, including cancer. The most significant changes at the genomic level (DNA damage, [...] Read more.
Aging is a natural, gradual, and inevitable process associated with a series of changes at the molecular, cellular, and tissue levels that can lead to an increased risk of many diseases, including cancer. The most significant changes at the genomic level (DNA damage, telomere shortening, epigenetic changes) and non-genomic changes are referred to as hallmarks of aging. The hallmarks of aging and cancer are intertwined. Many studies have focused on genomic hallmarks, but non-genomic hallmarks are also important and may additionally cause genomic damage and increase the expression of genomic hallmarks. Understanding the non-genomic hallmarks of aging and cancer, and how they are intertwined, may lead to the development of approaches that could influence these hallmarks and thus function not only to slow aging but also to prevent cancer. In this review, we focus on non-genomic changes. We discuss cell senescence, disruption of proteostasis, deregualation of nutrient sensing, dysregulation of immune system function, intercellular communication, mitochondrial dysfunction, stem cell exhaustion and dysbiosis. Full article
(This article belongs to the Special Issue Cancer Biomarker: Current Status and Future Perspectives)
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20 pages, 1474 KiB  
Review
The Role of Cocaine- and Amphetamine-Regulated Transcript (CART) in Cancer: A Systematic Review
by Maja Owe-Larsson, Jan Pawłasek, Tomasz Piecha, Alicja Sztokfisz-Ignasiak, Mikołaj Pater and Izabela R. Janiuk
Int. J. Mol. Sci. 2023, 24(12), 9986; https://doi.org/10.3390/ijms24129986 - 10 Jun 2023
Cited by 5 | Viewed by 2944
Abstract
The functions of cocaine- and amphetamine-regulated transcript (CART) neuropeptide encoded by the CARTPT gene vary from modifying behavior and pain sensitivity to being an antioxidant. Putative CART peptide receptor GPR160 was implicated recently in the pathogenesis of cancer. However, the exact role of [...] Read more.
The functions of cocaine- and amphetamine-regulated transcript (CART) neuropeptide encoded by the CARTPT gene vary from modifying behavior and pain sensitivity to being an antioxidant. Putative CART peptide receptor GPR160 was implicated recently in the pathogenesis of cancer. However, the exact role of CART protein in the development of neoplasms remains unclear. This systematic review includes articles retrieved from the Scopus, PubMed, Web of Science and Medline Complete databases. Nineteen publications that met the inclusion criteria and describe the association of CART and cancer were analyzed. CART is expressed in various types of cancer, e.g., in breast cancer and neuroendocrine tumors (NETs). The role of CART as a potential biomarker in breast cancer, stomach adenocarcinoma, glioma and some types of NETs was suggested. In various cancer cell lines, CARTPT acts an oncogene, enhancing cellular survival by the activation of the ERK pathway, the stimulation of other pro-survival molecules, the inhibition of apoptosis or the increase in cyclin D1 levels. In breast cancer, CART was reported to protect tumor cells from tamoxifen-mediated death. Taken together, these data support the role of CART activity in the pathogenesis of cancer, thus opening new diagnostic and therapeutic approaches in neoplastic disorders. Full article
(This article belongs to the Special Issue Cancer Biomarker: Current Status and Future Perspectives)
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Other

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9 pages, 898 KiB  
Case Report
Germline Variants in MLH1 and ATM Genes in a Young Patient with MSI-H in a Precancerous Colonic Lesion
by Antonio Nolano, Giovanni Battista Rossi, Valentina D’Angelo, Raffaella Liccardo, Marina De Rosa, Paola Izzo and Francesca Duraturo
Int. J. Mol. Sci. 2023, 24(6), 5970; https://doi.org/10.3390/ijms24065970 - 22 Mar 2023
Viewed by 5166
Abstract
Lynch syndrome (LS) is an autosomal dominant inherited disorder that primarily predisposes individuals to colorectal and endometrial cancer. It is associated with pathogenic variants in DNA mismatch repair (MMR) genes. In this study, we report the case of a 16-year-old boy who developed [...] Read more.
Lynch syndrome (LS) is an autosomal dominant inherited disorder that primarily predisposes individuals to colorectal and endometrial cancer. It is associated with pathogenic variants in DNA mismatch repair (MMR) genes. In this study, we report the case of a 16-year-old boy who developed a precancerous colonic lesion and had a clinical suspicion of LS. The proband was found to have a somatic MSI-H status. Analysis of the coding sequences and flanking introns of the MLH1 and MSH2 genes by Sanger sequencing led to the identification of the variant of uncertain significance, namely, c.589-9_589-6delGTTT in the MLH1 gene. Further investigation revealed that this variant was likely pathogenetic. Subsequent next-generation sequencing panel analysis revealed the presence of two variants of uncertain significance in the ATM gene. We conclude that the phenotype of our index case is likely the result of a synergistic effect of these identified variants. Future studies will allow us to understand how risk alleles in different colorectal-cancer-prone genes interact with each other to increase an individual’s risk of developing cancer. Full article
(This article belongs to the Special Issue Cancer Biomarker: Current Status and Future Perspectives)
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