Fusco, N.

Ghidini, M.

Marchio&apos

Scatena, C.

English

Marchio', C.

Institutional Research Information System University of Turin

genesG C A TT A C GG C A TEditorialSpecial Issue: Molecular Biomarkers in Solid TumorsNicola Fusco 1,2,* , Caterina Marchiò 3,4,* , Michele Ghidini 5,* and Cristian Scatena 6,*Citation: Fusco, N.; Marchiò, C.;Ghidini, M.; Scatena, C. Special Issue:Molecular Biomarkers in SolidTumors. Genes 2021, 12, 984. https://doi.org/10.3390/genes12070984Received: 18 June 2021Accepted: 24 June 2021Published: 28 June 2021Publisher’s Note: MDPI stays neutralwith regard to jurisdictional claims inpublished maps and institutional affil-iations.Copyright: © 2021 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).1 Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy2 Division of Pathology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy3 Department of Medical Sciences, University of Turin, 10124 Turin, Italy4 Division of Pathology, Candiolo Cancer Institute FPO-IRCCS, 10060 Candiolo, Italy5 Division of Medical Oncology, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico,20122 Milan, Italy6 Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery,University of Pisa, 56126 Pisa, Italy* Correspondence: nicola.fusco@unimi.it (N.F.); caterina.marchio@unito.it (C.M.);michele.ghidini@policlinico.mi.it (M.G.); cristian.scatena@unipi.it (C.S.)Diagnostic strategies using a next-generation systematic approach have the potentialto radically improve the outcome and subsequent quality of life of patients with cancer.Due to unprecedented technological developments, coupled with novel multidisciplinaryapproaches in translational research, a multitude of biomarkers at genomic, transcrip-tomic, proteomic, and immunologic levels have been discovered and validated [1]. Thesebiomarkers are strongly impacting pathology and treatment decision-making in oncology.We edited the present Special Issue of Genes on “Molecular Biomarkers in Solid Tumors”to provide a snapshot of newly available and/or bona fide biomarkers for the clinicalmanagement of patients with cancer. We aimed to offer a pathology-oriented angle onsome of the hot subjects regarding biomarker-based oncology. Particular attention has beenpaid to the selection of articles focusing on tailored biomarkers assessment in terms oftechnology and analytical strategies. The present collection that we had the pleasure to editconsists of three original research articles and eight reviews covering different biomarkersin different types of cancer.Four articles provide insights into the role of specific biomarkers in cancers usinga histology-agnostic approach. Among these, original research by Gianluca Lopez andcollaborators describes the prevalence and prognostic impact of somatic mutations inleucine-rich repeat kinase 2 (LRRK2), a major contributor to familial Parkinson’s disease, indifferent neoplastic settings [2]. Through the analysis of molecular data from 14,041 tumorsavailable at cBioPortal.org, they report a significantly different risk of death based onLRRK2 copy-number variations (CNV). These results may pave the way for new primaryand translational research studies to clarify the role of LRRK2, not only in neurodegenera-tive disorders, but also as a biomarker in oncology. Another interesting study by Khan andSarkar provides an elegant overview of the oncogene astrocyte elevated gene-1/metadherin(AEG-1/MTDH) role [3]. This work has been particularly welcomed by the Editorial Board,given that since its initial cloning in 2002, many studies corroborated the role of AEG-1/MTDH in different neoplastic settings. We believe that this wide range of informationis thoroughly analyzed by the authors. Similarly, many studies have recently providedevidence of the oncogenic activity of contactin 1 (CNTN1), a cell adhesion molecule, ina variety of cancer types. In this respect, Gu et al. clarify the current state of knowl-edge on CNTN1 biochemical mechanisms and interactions in various signaling pathwaysfrequently altered in cancer, including the phosphatidylinositol 3-kinase (PI3K)/proteinkinase B (Akt)/mammalian target of rapamycin (mTOR) [4]. Another gene that is deeplyinvolved in this pathway is represented by the tumor suppressor phosphatase and tensinhomolog (PTEN). Despite the actionability of PTEN alterations, their role as biomarkersremains controversial in clinical practice. In this Special Issue, we also present an updateGenes 2021, 12, 984. https://doi.org/10.3390/genes12070984 https://www.mdpi.com/journal/genesGenes 2021, 12, 984 2 of 3on the biologic and genetic alterations of PTEN across the most frequent solid tumors, aswell as on their actual and/or possible clinical applications [5].Then, we introduce a series of articles focusing on selected types of tumor. The Aus-tralian group of Allegra Freelander and colleagues summarizes the currently availabledata on prognostic, predictive, and pharmacodynamic molecular biomarkers in one of themost frequent types of tumor worldwide: the hormone receptor-positive breast cancer [6].Another big killer is addressed by Ouyang et al. in an original research article takingadvantage of multi-omics data analysis in liver cancer [7]. In this study, they propose anintegration of biostatistics methods for biomarker identification in an unbalanced datasetof hepatocellular carcinomas. With this approach, the authors obtain 34 differentiallyexpressed genes that may improve the pathological diagnosis of this tumor type. In the di-gestive system, pancreatic cancer is also a highly lethal condition due to its aggressivenessand limited treatment options. An international team of scientists summarizes the currentknowledge about novel immune-based therapies in this type of tumor, using microsatelliteinstability (MSI) as a predictive biomarker [8]. We would like to highlight that immunother-apy has also been widely explored in glioblastoma during the past few years. This tumorconsists of an admixture of malignant cells and stromal cells within a variably dense im-mune microenvironment. A review article that one of the Editors prepared for this SpecialIssue attempts to elucidate the complexity of glioblastoma microenvironment composition,highlighting the current state of the art in immunotherapy approaches [9]. Then, we se-lected a research article on cutaneous squamous cell carcinoma (SCC). Despite it being thesecond-most-common skin cancer in Caucasians, there is still a substantial lack of clinicallyreliable molecular biomarkers for this tumor. Hence, only clinicopathological prognosticmarkers are commonly used in the clinical workup of SCC, including tumor thickness andsize, depth of invasion, perineural invasion, degree of differentiation, location, stage. Forthis reason, we have applauded the study by Campos et al. on the prognostic significanceof p53 expression and RAS mutations in cutaneous SCC [10]. Immunohistochemistryfor p53 and mutational profiling for RAS on a retrospective series of 162 lesions from128 patients revealed that p53 overexpression and RAS mutations are a bona fide predictorof recurrence and local aggressiveness, respectively. Finally, we would like to offer to thereadership of this Special Issue two articles on malignancies affecting the urinary tract.A review by Cinque and colleagues provides insights into the role of circulating RNA(i.e., miRNA, lncRNAs, and circRNAs) as possible diagnostic and prognostic biomarkersof renal cancer [11], while De Lorenzis et al. stress the importance of high-throughputgenomic characterization in upper urinary tract urothelial carcinomas [12].Our understanding of the molecular landscape of solid tumors is expanding dayby day. We believe that a biomarker-based approach at a single-patient level in the riskassessment and treatment selection would represent a quantum leap for the community ofhealthcare providers and patients.Conflicts of Interest: The authors declare no conflict of interest.References1. Angerilli, V.; Galuppini, F.; Pagni, F.; Fusco, N.; Malapelle, U.; Fassan, M. The Role of the Pathologist in the Next-Generation Eraof Tumor Molecular Characterization. Diagnostics 2021, 11, 339. [CrossRef] [PubMed]2. Lopez, G.; Lazzeri, G.; Rappa, A.; Isimbaldi, G.; Cribiù, F.M.; Guerini-Rocco, E.; Ferrero, S.; Vaira, V.; Di Fonzo, A. ComprehensiveGenomic Analysis Reveals the Prognostic Role of LRRK2 Copy-Number Variations in Human Malignancies. Genes 2020, 11, 846.[CrossRef] [PubMed]3. Khan, M.; Sarkar, D. The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: AReview. Genes 2021, 12, 308. [CrossRef] [PubMed]4. Gu, Y.; Li, T.; Kapoor, A.; Major, P.; Tang, D. Contactin 1: An Important and Emerging Oncogenic Protein Promoting CancerProgression and Metastasis. Genes 2020, 11, 874. [CrossRef] [PubMed]5. Fusco, N.; Sajjadi, E.; Venetis, K.; Gaudioso, G.; Lopez, G.; Corti, C.; Rocco, E.G.; Criscitiello, C.; Malapelle, U.; Invernizzi, M.PTEN Alterations and Their Role in Cancer Management: Are We Making Headway on Precision Medicine? Genes 2020, 11, 719.[CrossRef] [PubMed]Genes 2021, 12, 984 3 of 36. Freelander, A.; Brown, L.J.; Parker, A.; Segara, D.; Portman, N.; Lau, B.; Lim, E. Molecular Biomarkers for Contemporary Therapiesin Hormone Receptor-Positive Breast Cancer. Genes 2021, 12, 285. [CrossRef] [PubMed]7. Ouyang, X.; Fan, Q.; Ling, G.; Shi, Y.; Hu, F. Identification of Diagnostic Biomarkers and Subtypes of Liver HepatocellularCarcinoma by Multi-Omics Data Analysis. Genes 2020, 11, 1051. [CrossRef]8. Ghidini, M.; Lampis, A.; Mirchev, M.B.; Okuducu, A.F.; Ratti, M.; Valeri, N.; Hahne, J.C. Immune-Based Therapies and the Role ofMicrosatellite Instability in Pancreatic Cancer. Genes 2021, 12, 33. [CrossRef]9. Fanelli, G.N.; Grassini, D.; Ortenzi, V.; Pasqualetti, F.; Montemurro, N.; Perrini, P.; Naccarato, A.G.; Scatena, C. Decipher theGlioblastoma Microenvironment: The First Milestone for New Groundbreaking Therapeutic Strategies. Genes 2021, 12, 445.[CrossRef]10. Campos, M.A.; Macedo, S.; Fernandes, M.S.; Pestana, A.; Pardal, J.; Batista, R.; Vinagre, J.; Sanches, A.; Baptista, A.;Lopes, J.M.; et al. Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas. Genes2020, 11, 751. [CrossRef] [PubMed]11. Cinque, A.; Vago, R.; Trevisani, F. Circulating RNA in Kidney Cancer: What We Know and What We Still Suppose. Genes 2021, 12,835. [CrossRef] [PubMed]12. De Lorenzis, E.; Albo, G.; Longo, F.; Bebi, C.; Boeri, L.; Montanari, E. Current Knowledge on Genomic Profiling of Upper TractUrothelial Carcinoma. Genes 2021, 12, 333. [CrossRef] [PubMed]

Special issue: Molecular biomarkers in solid tumors

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Special issue: Molecular biomarkers in solid tumors

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