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Cancers
Special Issues
Diagnostic and Predictive Biomarkers in Lung Cancer
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Diagnostic and Predictive Biomarkers in Lung Cancer

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

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 51643

Special Issue Editors

Dr. Massimo Barberis

E-Mail Website
Guest Editor
Istituto Europeo di Oncologia, Milan, Italy
Interests: molecular pathology; thoracic oncology; laboratory management
Dr. Caterina Fumagalli

E-Mail
Guest Editor
Istituto Europeo di Oncologia, IRCCS, Milan, Italy
Interests: molecular pathology; biomarkers

Special Issue Information

Dear Colleagues,

Despite advances in treatment, lung cancer remains the most frequent cause of cancer-related mortality worldwide, with a 5-year relative survival rate of 24% for all stages. A critical issue related to improvement in patient outcomes will be the ability to define tumor genetic profiles, allowing personalized therapeutic decisions to be made.

Indeed, in the era of targeted and immuno-therapies, new drugs are becoming available and those on the market are starting to be used in combination or sequentially to overcome resistance mechanisms. The great challenge for the pathologist is to guide treatment accurately, which involves going beyond diagnosis and tumor classification and giving clinically useful diagnostic, prognostic, and predictive parameters in a time frame consistent with clinical needs.

In this view, the development of a comprehensive genomic profile moving beyond the standard-of-care EGFR/ALK/ROS1 and PD-L1 evaluations has been under investigation. Moreover, new predictive biomarkers for immunotherapy responses, such as Tumor Mutational Burden (TMB) and Tumor Infiltrating Lymphocytes (TILs), or the evaluation of symbiotic microorganisms living in the gut (microbiota) have recently been explored.

Unfortunately, up to 70% of patients with NSCLC are diagnosed at advanced stages and tissue biopsies often cannot be taken; therefore, tumor molecular profiling should be performed using different sources as cytological samples obtained with the EBUS-TBNA (endobronchial ultrasound-guided trans-bronchial needle aspiration) technique. In this regard, rapid on-site evaluation (ROSE) by cytopathologists has improved the adequacy and management of cytology samples for morphological, phenotypical, and molecular testing.

Moreover, liquid biopsy, which is based on the detection of tumor-related biomarkers from body fluids such as the peripheral blood, is a relatively new, very promising tool that could capture spatial and temporal intra-tumoral heterogeneity.

Lastly, the evolving molecular landscape of neuroendocrine tumors of the lung, mainly Small Cell Lung Cancers (SCLC) and Large Cell Neuroendocrine Carcinomas (LCNEC) deserves a special mention for its therapeutic implications. Different chemotherapy schemes according to molecular biomarkers could offer new opportunities to patients with LCNEC.

This Special Issue of Cancers will highlight the current state-of-the-art technology in diagnostic and predictive assays used for lung cancer with special emphasis on future prospects in early diagnosis, biomarker integration, and tumor response evaluation.

Dr. Massimo Barberis
Dr. Caterina Fumagalli
Guest Editors

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

  • NSCLC
  • Neuroendocrine carcinoma
  • Biomarkers
  • Comprehensive molecular profile

Published Papers (15 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 174 KiB  
Editorial
Diagnostic and Predictive Biomarkers in Lung Cancer
by Caterina Fumagalli and Massimo Barberis
Cancers 2021, 13(11), 2577; https://doi.org/10.3390/cancers13112577 - 25 May 2021
Cited by 3 | Viewed by 1688
Abstract
Lung cancer is the most frequent cause of cancer-related mortality worldwide [...] Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
5 pages, 578 KiB  
Editorial
Making the Most of Complexity to Create Opportunities: Comprehensive Genomic Profiling and Molecular Tumor Board for Patients with Non-Small Cell Lung Cancer (NSCLC)
by Caterina Fumagalli, Elena Guerini-Rocco and Massimo Barberis
Cancers 2021, 13(4), 609; https://doi.org/10.3390/cancers13040609 - 04 Feb 2021
Cited by 3 | Viewed by 2196
Abstract
Personalized cancer therapy matches the plan of treatment with specific molecular alterations [...] Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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Research

Jump to: Editorial, Review, Other

11 pages, 1443 KiB  
Article
Genomic Characterization of Concurrent Alterations in Non-Small Cell Lung Cancer (NSCLC) Harboring Actionable Mutations
by Antonio Passaro, Ilaria Attili, Alessandra Rappa, Davide Vacirca, Alberto Ranghiero, Caterina Fumagalli, Juliana Guarize, Lorenzo Spaggiari, Filippo de Marinis, Massimo Barberis and Elena Guerini-Rocco
Cancers 2021, 13(9), 2172; https://doi.org/10.3390/cancers13092172 - 30 Apr 2021
Cited by 24 | Viewed by 3055
Abstract
An increasing number of driver genomic alterations with potential targeted treatments have been identified in non-small cell lung cancer (NSCLC). Much less is known about the incidence and different distribution of concurrent alterations, as identified by comprehensive genomic profiling in oncogene-addicted NSCLCs. Genomic [...] Read more.
An increasing number of driver genomic alterations with potential targeted treatments have been identified in non-small cell lung cancer (NSCLC). Much less is known about the incidence and different distribution of concurrent alterations, as identified by comprehensive genomic profiling in oncogene-addicted NSCLCs. Genomic data from advanced NSCLC consecutively analyzed using a broad next-generation sequencing panel were retrospectively collected. Tumors harboring at least one main actionable gene alteration were categorized according to the presence/absence of concurrent genomic aberrations, to evaluate different patterns among the main oncogene-addicted NSCLCs. Three-hundred-nine actionable gene alterations were identified in 284 advanced NSCLC patients during the study period. Twenty-five tumor samples (8%) displayed concurrent alterations in actionable genes. Co-occurrences involving any pathogenic variant or copy number variation (CNV) were identified in 82.8% of cases. Overall, statistically significant differences in the number of concurrent alterations, and the distribution of TP53, STK11, cyclines and receptor tyrosin kinase (RTK) aberrations were observed across the eight actionable gene groups. NGS analyses of oncogene-addicted NSCLCs showed a different distribution and pattern of co-alteration profiles. Further investigations are needed to evaluate the prognostic and treatment-related impact of these concurrent alterations, hooked to the main gene aberrations. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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11 pages, 1707 KiB  
Article
Physiological Biomarkers Assessed by Low-Tech Exercise Tests Predict Complications and Overall Survival in Patients Undergoing Pneumonectomy Due to Lung Cancer
by Tomasz Marjanski, Damian Wnuk, Robert Dziedzic, Marcin Ostrowski, Wioletta Sawicka, Ewa Marjanska and Witold Rzyman
Cancers 2021, 13(4), 735; https://doi.org/10.3390/cancers13040735 - 10 Feb 2021
Cited by 7 | Viewed by 1872
Abstract
Due to its debilitating character pneumonectomy this is last-resort procedure. Preoperative results of the 6-min walking test (6MWT) help to identify high risk of postoperative complications and increased mortality in patients undergoing lobectomy for lung cancer. The aim of the study was to [...] Read more.
Due to its debilitating character pneumonectomy this is last-resort procedure. Preoperative results of the 6-min walking test (6MWT) help to identify high risk of postoperative complications and increased mortality in patients undergoing lobectomy for lung cancer. The aim of the study was to validate the value of 500 m in 6MWT as an indicator, which differentiates risk of complications in patients undergoing pneumonectomy. 125 patients who underwent pneumonectomy at Thoracic Surgery Department between 2009 and 2018. On the day preceding the surgery, patients underwent 6MWT. The patients were in median age of 63 years. The cut-off value of 500 m identified patients with increased 90-day mortality [17.9% vs. 3.5%, odds ratio (OR) 6.271, 95% confidence interval (CI) 1.528–25.739], first-year mortality (30.7% vs. 11.6%, OR 3.378, 95% CI 1.310–8.709), and overall survival (p = 0.02). Patients who covered a distance ≤ 500 m had an increased risk of atrial fibrillation (35.9% vs. 16.3%, OR 2.880, 95% CI 1.207–6.870) and cardiac complications (38.4% vs. 19.8%, OR 2.537, 95% CI 1.100–5.849). Patients unable to reach 500 m in 6MWT are in a high risk of postoperative death after pneumonectomy, what may be a result of increased frequency of postoperative cardiac complications. Poor result of 6MWT is a predictor of worse overall survival. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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9 pages, 1678 KiB  
Communication
Serum Concentrations of KL-6 in Patients with IPF and Lung Cancer and Serial Measurements of KL-6 in IPF Patients Treated with Antifibrotic Therapy
by Miriana d’Alessandro, Laura Bergantini, Paolo Cameli, Maria Pieroni, Rosa Metella Refini, Piersante Sestini and Elena Bargagli
Cancers 2021, 13(4), 689; https://doi.org/10.3390/cancers13040689 - 09 Feb 2021
Cited by 24 | Viewed by 2828
Abstract
Background: Krebs von den Lungen-6 (KL-6) was suggested as ILD biomarker including idiopathic pulmonary fibrosis (IPF). Lung cancer is one of the most severe comorbidity of IPF patients. This study aims to serially analyze KL-6 in IPF patients after 24 months of Nintedanib [...] Read more.
Background: Krebs von den Lungen-6 (KL-6) was suggested as ILD biomarker including idiopathic pulmonary fibrosis (IPF). Lung cancer is one of the most severe comorbidity of IPF patients. This study aims to serially analyze KL-6 in IPF patients after 24 months of Nintedanib and to first investigate the biomarker behavior in IPF associated with adenocarcinoma. Materials and methods: One hundred and forty-two ILD patients (median (IQR), 69 (63–75) years; 86 males) were retrospectively enrolled. Serial serum samples were collected from IPF patients before starting antifibrotic therapy and after 12 months. Serum KL-6 levels were measured by KL-6 reagent assay (Fujirebio Europe, UK). Results: Increased KL-6 concentrations were identified in IPF-LC patients than IPF, fibrotic hypersensitivity pneumonitis, and pulmonary fibrosis associated with autoimmune disease groups. A cut-off value was calculated to distinguish IPF and IPF-LC patients. IPF patients monitored for 24 months with Nintedanib showed persisted increased levels of KL-6 with a progressive decline of FVC percentages. Conclusion: This preliminary study offers a first demonstration that very high serum concentrations of KL-6 in IPF-LC patients are associated with poor prognosis. Moreover, serial evaluation of serum KL-6 in IPF patients over 24 months of Nintedanib treatment revealed that most patients experienced a stabilization of lung function parameters and of serum concentrations of KL-6. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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14 pages, 1316 KiB  
Article
RNA-Based Assay for Next-Generation Sequencing of Clinically Relevant Gene Fusions in Non-Small Cell Lung Cancer
by Caterina De Luca, Francesco Pepe, Antonino Iaccarino, Pasquale Pisapia, Luisella Righi, Angela Listì, Lorenza Greco, Gianluca Gragnano, Severo Campione, Gianfranco De Dominicis, Fabio Pagni, Roberta Sgariglia, Mariantonia Nacchio, Rossella Tufano, Floriana Conticelli, Elena Vigliar, Claudio Bellevicine, Diego Luigi Cortinovis, Silvia Novello, Miguel Angel Molina-Vila, Rafael Rosell, Giancarlo Troncone and Umberto Malapelleadd Show full author list remove Hide full author list
Cancers 2021, 13(1), 139; https://doi.org/10.3390/cancers13010139 - 04 Jan 2021
Cited by 18 | Viewed by 3962
Abstract
Gene fusions represent novel predictive biomarkers for advanced non-small cell lung cancer (NSCLC). In this study, we validated a narrow NGS gene panel able to cover therapeutically-relevant gene fusions and splicing events in advanced-stage NSCLC patients. To this aim, we first assessed minimal [...] Read more.
Gene fusions represent novel predictive biomarkers for advanced non-small cell lung cancer (NSCLC). In this study, we validated a narrow NGS gene panel able to cover therapeutically-relevant gene fusions and splicing events in advanced-stage NSCLC patients. To this aim, we first assessed minimal complementary DNA (cDNA) input and the limit of detection (LoD) in different cell lines. Then, to evaluate the feasibility of applying our panel to routine clinical samples, we retrospectively selected archived lung adenocarcinoma histological and cytological (cell blocks) samples. Overall, our SiRe RNA fusion panel was able to detect all fusions and a splicing event harbored in a RNA pool diluted up to 2 ng/µL. It also successfully analyzed 46 (95.8%) out of 48 samples. Among these, 43 (93.5%) out of 46 samples reproduced the same results as those obtained with conventional techniques. Intriguingly, the three discordant results were confirmed by a CE-IVD automated real-time polymerase chain reaction (RT-PCR) analysis (Easy PGX platform, Diatech Pharmacogenetics, Jesi, Italy). Based on these findings, we conclude that our new SiRe RNA fusion panel is a valid and robust tool for the detection of clinically relevant gene fusions and splicing events in advanced NSCLC. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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18 pages, 4862 KiB  
Article
DrugSniper, a Tool to Exploit Loss-Of-Function Screens, Identifies CREBBP as a Predictive Biomarker of VOLASERTIB in Small Cell Lung Carcinoma (SCLC)
by Fernando Carazo, Cristina Bértolo, Carlos Castilla, Xabier Cendoya, Lucía Campuzano, Diego Serrano, Marian Gimeno, Francisco J. Planes, Ruben Pio, Luis M. Montuenga and Angel Rubio
Cancers 2020, 12(7), 1824; https://doi.org/10.3390/cancers12071824 - 07 Jul 2020
Cited by 6 | Viewed by 3404
Abstract
The development of predictive biomarkers of response to targeted therapies is an unmet clinical need for many antitumoral agents. Recent genome-wide loss-of-function screens, such as RNA interference (RNAi) and CRISPR-Cas9 libraries, are an unprecedented resource to identify novel drug targets, reposition drugs and [...] Read more.
The development of predictive biomarkers of response to targeted therapies is an unmet clinical need for many antitumoral agents. Recent genome-wide loss-of-function screens, such as RNA interference (RNAi) and CRISPR-Cas9 libraries, are an unprecedented resource to identify novel drug targets, reposition drugs and associate predictive biomarkers in the context of precision oncology. In this work, we have developed and validated a large-scale bioinformatics tool named DrugSniper, which exploits loss-of-function experiments to model the sensitivity of 6237 inhibitors and predict their corresponding biomarkers of sensitivity in 30 tumor types. Applying DrugSniper to small cell lung cancer (SCLC), we identified genes extensively explored in SCLC, such as Aurora kinases or epigenetic agents. Interestingly, the analysis suggested a remarkable vulnerability to polo-like kinase 1 (PLK1) inhibition in CREBBP-mutant SCLC cells. We validated this association in vitro using four mutated and four wild-type SCLC cell lines and two PLK1 inhibitors (Volasertib and BI2536), confirming that the effect of PLK1 inhibitors depended on the mutational status of CREBBP. Besides, DrugSniper was validated in-silico with several known clinically-used treatments, including the sensitivity of Tyrosine Kinase Inhibitors (TKIs) and Vemurafenib to FLT3 and BRAF mutant cells, respectively. These findings show the potential of genome-wide loss-of-function screens to identify new personalized therapeutic hypotheses in SCLC and potentially in other tumors, which is a valuable starting point for further drug development and drug repositioning projects. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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18 pages, 1916 KiB  
Article
Novel Liquid Biomarker Panels for A Very Early Response Capturing of NSCLC Therapies in Advanced Stages
by Florian Janke, Farastuk Bozorgmehr, Sabine Wrenger, Steffen Dietz, Claus P. Heussel, Gudula Heussel, Carlos F. Silva, Stephan Rheinheimer, Manuel Feisst, Michael Thomas, Heiko Golpon, Andreas Günther, Holger Sültmann, Thomas Muley, Sabina Janciauskiene, Michael Meister and Marc A. Schneider
Cancers 2020, 12(4), 954; https://doi.org/10.3390/cancers12040954 - 12 Apr 2020
Cited by 3 | Viewed by 4749
Abstract
Computed tomography (CT) scans are the gold standard to measure treatment success of non-small cell lung cancer (NSCLC) therapies. Here, we investigated the very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid [...] Read more.
Computed tomography (CT) scans are the gold standard to measure treatment success of non-small cell lung cancer (NSCLC) therapies. Here, we investigated the very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from 50 patients were taken at baseline and at three early time points after therapy initiation. DNA mutations, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved cytokeratin 18 (M30 antigen), and soluble cytokeratin 18 (M65 antigen) were measured in serum and plasma samples. Baseline and first follow-up CT scans were evaluated and correlated with biomarker data. The detection rate of the individual biomarkers was between 56% and 100%. While only keratin 18 correlated with the tumor load at baseline, we found several individual markers correlating with the tumor response to treatment for each of the three time points of blood draws. A combination of the five best markers at each time point resulted in highly significant marker panels indicating therapeutic response (R2 = 0.78, R2 = 0.71, and R2 = 0.71). Our study demonstrates that an early measurement of biomarkers immediately after therapy start can assess tumor response to treatment and might support an adaptation of treatment to improve patients’ outcome. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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Review

Jump to: Editorial, Research, Other

19 pages, 1976 KiB  
Review
Next-Generation Sequencing with Liquid Biopsies from Treatment-Naïve Non-Small Cell Lung Carcinoma Patients
by Paul Hofman
Cancers 2021, 13(9), 2049; https://doi.org/10.3390/cancers13092049 - 23 Apr 2021
Cited by 18 | Viewed by 3797
Abstract
Recently, the liquid biopsy (LB), a non-invasive and easy to repeat approach, has started to compete with the tissue biopsy (TB) for detection of targets for administration of therapeutic strategies for patients with advanced stages of lung cancer at tumor progression. A LB [...] Read more.
Recently, the liquid biopsy (LB), a non-invasive and easy to repeat approach, has started to compete with the tissue biopsy (TB) for detection of targets for administration of therapeutic strategies for patients with advanced stages of lung cancer at tumor progression. A LB at diagnosis of late stage non-small cell lung carcinoma (NSCLC) is also being performed. It may be asked if a LB can be complementary (according to the clinical presentation or systematics) or even an alternative to a TB for treatment-naïve advanced NSCLC patients. Nucleic acid analysis with a TB by next-generation sequencing (NGS) is gradually replacing targeted sequencing methods for assessment of genomic alterations in lung cancer patients with tumor progression, but also at baseline. However, LB is still not often used in daily practice for NGS. This review addresses different aspects relating to the use of LB for NGS at diagnosis in advanced NSCLC, including its advantages and limitations. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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19 pages, 289 KiB  
Review
From Tumor Mutational Burden to Blood T Cell Receptor: Looking for the Best Predictive Biomarker in Lung Cancer Treated with Immunotherapy
by Andrea Sesma, Julián Pardo, Mara Cruellas, Eva M. Gálvez, Marta Gascón, Dolores Isla, Luis Martínez-Lostao, Maitane Ocáriz, José Ramón Paño, Elisa Quílez, Ariel Ramírez, Irene Torres-Ramón, Alfonso Yubero, María Zapata and Rodrigo Lastra
Cancers 2020, 12(10), 2974; https://doi.org/10.3390/cancers12102974 - 14 Oct 2020
Cited by 18 | Viewed by 3027
Abstract
Despite therapeutic advances, lung cancer (LC) is one of the leading causes of cancer morbidity and mortality worldwide. Recently, the treatment of advanced LC has experienced important changes in survival benefit due to immune checkpoint inhibitors (ICIs). However, overall response rates (ORR) remain [...] Read more.
Despite therapeutic advances, lung cancer (LC) is one of the leading causes of cancer morbidity and mortality worldwide. Recently, the treatment of advanced LC has experienced important changes in survival benefit due to immune checkpoint inhibitors (ICIs). However, overall response rates (ORR) remain low in unselected patients and a large proportion of patients undergo disease progression in the first weeks of treatment. Therefore, there is a need of biomarkers to identify patients who will benefit from ICIs. The programmed cell death ligand 1 (PD-L1) expression has been the first biomarker developed. However, its use as a robust predictive biomarker has been limited due to the variability of techniques used, with different antibodies and thresholds. In this context, tumor mutational burden (TMB) has emerged as an additional powerful biomarker based on the observation of successful response to ICIs in solid tumors with high TMB. TMB can be defined as the total number of nonsynonymous mutations per DNA megabases being a mechanism generating neoantigens conditioning the tumor immunogenicity and response to ICIs. However, the latest data provide conflicting results regarding its role as a biomarker. Moreover, considering the results of the recent data, the use of peripheral blood T cell receptor (TCR) repertoire could be a new predictive biomarker. This review summarises recent findings describing the clinical utility of TMB and TCRβ (TCRB) and concludes that immune, neontigen, and checkpoint targeted variables are required in combination for accurately identifying patients who most likely will benefit of ICIs. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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Graphical abstract

16 pages, 1792 KiB  
Review
Beyond Traditional Morphological Characterization of Lung Neuroendocrine Neoplasms: In Silico Study of Next-Generation Sequencing Mutations Analysis across the Four World Health Organization Defined Groups
by Giovanni Centonze, Davide Biganzoli, Natalie Prinzi, Sara Pusceddu, Alessandro Mangogna, Elena Tamborini, Federica Perrone, Adele Busico, Vincenzo Lagano, Laura Cattaneo, Gabriella Sozzi, Luca Roz, Elia Biganzoli and Massimo Milione
Cancers 2020, 12(10), 2753; https://doi.org/10.3390/cancers12102753 - 24 Sep 2020
Cited by 12 | Viewed by 3069
Abstract
Lung neuroendocrine neoplasms (LNENs) represent a rare and heterogeneous population of lung tumors. LNENs incidence rate has increased dramatically over the past 30 years. The current World Health Organization LNENs classification (WHO 2015), distinguished four LNENs prognostic categories, according to their morphology, necrosis [...] Read more.
Lung neuroendocrine neoplasms (LNENs) represent a rare and heterogeneous population of lung tumors. LNENs incidence rate has increased dramatically over the past 30 years. The current World Health Organization LNENs classification (WHO 2015), distinguished four LNENs prognostic categories, according to their morphology, necrosis amount and mitotic count: typical carcinoid (TC), atypical-carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC). At present, due to their rarity and biological heterogeneity there is still no consensus on the best therapeutic approach. Next-generation-sequencing analysis showed that WHO 2015 LNENs classes, could be characterized also by specific molecular alterations: frequently mutated genes involving chromatin remodeling and generally characterized by low mutational burden (MB) are frequently detected in both TC and AC; otherwise, TP53 and RB1 tumor suppressor genes alterations and high MB are usually detected in LCNEC and SCLC. We provide an overview concerning gene mutations in each WHO 2015 LNENs class in order to report the current LNENs mutational status as potential tool to better understand their clinical outcome and to drive medical treatment. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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24 pages, 419 KiB  
Review
Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe
by Giulia Veronesi, David R. Baldwin, Claudia I. Henschke, Simone Ghislandi, Sergio Iavicoli, Matthijs Oudkerk, Harry J. De Koning, Joseph Shemesh, John K. Field, Javier J. Zulueta, Denis Horgan, Lucia Fiestas Navarrete, Maurizio Valentino Infante, Pierluigi Novellis, Rachael L. Murray, Nir Peled, Cristiano Rampinelli, Gaetano Rocco, Witold Rzyman, Giorgio Vittorio Scagliotti, Martin C. Tammemagi, Luca Bertolaccini, Natthaya Triphuridet, Rowena Yip, Alexia Rossi, Suresh Senan, Giuseppe Ferrante, Kate Brain, Carlijn van der Aalst, Lorenzo Bonomo, Dario Consonni, Jan P. Van Meerbeeck, Patrick Maisonneuve, Silvia Novello, Anand Devaraj, Zaigham Saghir and Giuseppe Pelosiadd Show full author list remove Hide full author list
Cancers 2020, 12(6), 1672; https://doi.org/10.3390/cancers12061672 - 24 Jun 2020
Cited by 45 | Viewed by 6977
Abstract
Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions [...] Read more.
Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)

Other

14 pages, 2654 KiB  
Systematic Review
Systematic Review and Metanalysis of Oncomarkers in IPF Patients and Serial Changes of Oncomarkers in a Prospective Italian Real-Life Case Series
by Miriana d’Alessandro, Laura Bergantini, Elena Torricelli, Paolo Cameli, Federico Lavorini, Maria Pieroni, Rosa Metella Refini, Piersante Sestini and Elena Bargagli
Cancers 2021, 13(3), 539; https://doi.org/10.3390/cancers13030539 - 31 Jan 2021
Cited by 15 | Viewed by 2650
Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is a severe progressive interstitial lung disease. At 5-year follow-up, 15% of IPF patients develop lung cancer, which significantly reduces the survival rate. Here we review the literature on the clinical role of oncomarkers in IPF progression, and [...] Read more.
Background: Idiopathic pulmonary fibrosis (IPF) is a severe progressive interstitial lung disease. At 5-year follow-up, 15% of IPF patients develop lung cancer, which significantly reduces the survival rate. Here we review the literature on the clinical role of oncomarkers in IPF progression, and describe the trend of routine oncomarkers in IPF patients over the longest follow-up yet reported. Materials and methods: A systematic search of the literature in PubMed was performed to find relevant studies published up to 24 September 2020. The most common oncomarkers were chosen to select papers related to pulmonary fibrosis. Then, 24 IPF patients and 25 non-IPF patients, followed at Careggi ILD Referral Centre and Siena Regional Referral Centre for ILD, were enrolled consecutively. Results: A few studies reported an association between serum oncomarkers and severity of IPF. NSE, CEA, Ca19.9, and Ca125 were higher in the IPF, than in the non-IPF, group at every follow-up (p < 0.05). Ca15.3 concentrations were higher in the IPF, than the non-IPF, group at t3 (p = 0.0080) and t4 (p = 0.0168). To improve the specificity and sensitivity of Ca15.3, a panel of biomarkers was analyzed, with the IPF group as dependent variable, and chitotriosidase, Cyfra 21.1, Ca15.3, Ca125, and Ca19.9 as independent variables. Conclusions: This study focused on the discovery of multiple biomarker signatures, such as combinations of oncomarkers, that are widely and routinely available in biochemistry laboratories. The combination of clinical parameters and biological markers could help achieve more accurate results regarding prognosis and response to treatment in IPF. Our results could pave the way for a more “personalized” medical approach to patients affected by IPF. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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17 pages, 2907 KiB  
Systematic Review
Functional Signatures in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Sex-Based Differences in Transcriptomic Studies
by Irene Pérez-Díez, Marta R. Hidalgo, Pablo Malmierca-Merlo, Zoraida Andreu, Sergio Romera-Giner, Rosa Farràs, María de la Iglesia-Vayá, Mariano Provencio, Atocha Romero and Francisco García-García
Cancers 2021, 13(1), 143; https://doi.org/10.3390/cancers13010143 - 05 Jan 2021
Cited by 10 | Viewed by 4202
Abstract
While studies have established the existence of differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a [...] Read more.
While studies have established the existence of differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a meta-analysis of transcriptomic data. We performed a meta-analysis of the functional profiling of nine public datasets that included 1366 samples from Gene Expression Omnibus and The Cancer Genome Atlas databases. Meta-analysis results from data merged, normalized, and corrected for batch effect show an enrichment for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to the immune response, nucleic acid metabolism, and purinergic signaling. We discovered the overrepresentation of terms associated with the immune response, particularly with the acute inflammatory response, and purinergic signaling in female lung adenocarcinoma patients, which could influence reported clinical differences. Further evaluations of the identified differential biological processes and pathways could lead to the discovery of new biomarkers and therapeutic targets. Our findings also emphasize the relevance of sex-specific analyses in biomedicine, which represents a crucial aspect influencing biological variability in disease. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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Perspective
Molecular and Genomic Profiling of Lung Cancer in the Era of Precision Medicine: A Position Paper from the Italian Association of Thoracic Oncology (AIOT)
by Nicola Normanno, Massimo Barberis, Filippo De Marinis, Cesare Gridelli and on the behalf of the AIOT Expert Panel
Cancers 2020, 12(6), 1627; https://doi.org/10.3390/cancers12061627 - 19 Jun 2020
Cited by 9 | Viewed by 2579
Abstract
The identification of the optimal cancer treatment has become progressively more intricate for non-small-cell lung cancer (NSCLC) patients due to the multitude of options available. The testing of biomarkers to predict clinical responses to therapies is pivotal to stratify the patients based on [...] Read more.
The identification of the optimal cancer treatment has become progressively more intricate for non-small-cell lung cancer (NSCLC) patients due to the multitude of options available. The testing of biomarkers to predict clinical responses to therapies is pivotal to stratify the patients based on the molecular features of their tumors. The number of actionable genetic alterations to be tested is increasing together with the comprehension of the molecular mechanisms underlying tumor growth and development. The possibility of using next generation sequencing-based approaches enhanced the acquisition of genetic data with potential clinical usefulness, and favored the integration of precision medicine in clinical practice. The availability of targeted sequencing panels that cover genetic alterations in hundreds of genes allows the performance of a comprehensive genomic profiling (CGP) of lung tumors. However, different issues still need to be solved, from the tissue needed for next generation sequencing analysis, to the choice of the test and its interpretation in the clinical context. This position paper from the Italian Association of Thoracic Oncology (AIOT) summarizes the results of a discussion from a Precision Medicine Panel meeting on the challenges to bringing CGP and, therefore, precision medicine into the daily clinical practice. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
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