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Cancers
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Predictive Biomarkers for Lung Cancer
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Predictive Biomarkers for Lung Cancer

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

Deadline for manuscript submissions: 31 January 2025 | Viewed by 9452

Special Issue Editor

Prof. Dr. Ole Hilberg

E-Mail Website
Guest Editor
Sygehus Lillebælt, Vejle Sygehus Beriderbakken 4, 7100 Vejle, Denmark
Interests: lung cancer; biomarker

Special Issue Information

Dear Colleagues,

Lung cancer remains a formidable challenge in oncology, characterized by its diverse subtypes and often aggressive nature. The intricate landscape of lung malignancies, encompassing non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and various histological subtypes, underscores the need for precise diagnostic and therapeutic strategies. Despite advancements in treatment modalities, the prognosis for many lung cancer patients remains poor, necessitating innovative approaches for early detection and tailored interventions.

In recent years, the role of biomarkers has emerged as a critical frontier in the pursuit of more effective lung cancer management. Biomarkers, ranging from genetic mutations and expression profiles to circulating molecules, hold the promise of revolutionizing both diagnostic precision and treatment outcomes. This Special Issue of the journal Cancers delves into the evolving landscape of biomarker research in lung cancer, aiming to shed light on recent breakthroughs and future directions in this dynamic field.

The advent of targeted therapies has redefined the treatment paradigm for certain subsets of lung cancer, with actionable mutations such as EGFR, ALK, and ROS1 paving the way for personalized medicine. The exploration of novel biomarkers, both predictive and prognostic, is expanding the repertoire of precision therapies. Additionally, immune checkpoint inhibitors have ushered in a new era in the immunotherapy landscape for lung cancer, offering unprecedented responses in a subset of patients.

However, challenges persist, particularly in the context of identifying biomarkers that transcend histological boundaries and predicting treatment responses in the heterogeneous landscape of lung cancer. The search for reliable biomarkers for early detection and monitoring of treatment responses is a focal point of ongoing research.

In this collection of articles, we present an overview of the current state of biomarker research in lung cancer, exploring the significance of emerging markers such as tumor mutational burden, PD-L1 expression, and liquid-biopsy-based approaches. As we navigate the complex terrain of lung cancer biomarkers, the articles within this Special Issue aim to provide valuable insights into the ongoing efforts to unravel the intricacies of this challenging disease. From predictive markers guiding targeted therapies to the dynamic landscape of immunotherapy, we invite readers to explore the forefront of biomarker-driven precision medicine in lung cancer.

Prof. Dr. Ole Hilberg
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 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.

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Published Papers (5 papers)

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12 pages, 1632 KiB  
Article
Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio: Side by Side with Molecular Mutations in Patients with Non-Small Cell Lung Cancer—The INOLUNG Study
by Corina Eugenia Budin, Iuliu Gabriel Cocuz, Liviu Sorin Enache, Ionuț Alexandru Rența, Cristian Cazacu, Dariana Elena Pătrîntașu, Mihai Olteanu, Ruxandra-Mioara Râjnoveanu, Edith Simona Ianoși, Armand Râjnoveanu and Ovidiu Simion Cotoi
Cancers 2024, 16(16), 2903; https://doi.org/10.3390/cancers16162903 - 21 Aug 2024
Viewed by 770
Abstract
Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelet/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș involving patients with lung cancer. The [...] Read more.
Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelet/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș involving patients with lung cancer. The parameters analyzed included histopathological type (NSCLC: squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters, and associated comorbidities. Results: A total of 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5.30 versus 2.60, p < 0.001; 217 versus 136, p < 0.001, respectively). NLR and PLR differ between men and women (p = 0.005 and p = 0.056, respectively). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusions: The NLR and PLR values may serve as new predictive biomarkers for the diagnosis of disease in patients with lung cancer, especially those with NSCLC. Full article
(This article belongs to the Special Issue Predictive Biomarkers for Lung Cancer)
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12 pages, 861 KiB  
Article
Baseline Cell-Free DNA Can Predict Malignancy of Nodules Observed in the ITALUNG Screening Trial
by Simonetta Bisanzi, Donella Puliti, Giulia Picozzi, Chiara Romei, Francesco Pistelli, Annalisa Deliperi, Giulia Carreras, Giovanna Masala, Giuseppe Gorini, Marco Zappa, Cristina Sani, Laura Carrozzi, Eugenio Paci, Rudolf Kaaks, Francesca Maria Carozzi and Mario Mascalchi
Cancers 2024, 16(12), 2276; https://doi.org/10.3390/cancers16122276 - 19 Jun 2024
Viewed by 870
Abstract
The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects [...] Read more.
The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects of the ITALUNG trial, including 29 subjects with screen-detected LC (17 prevalent and 12 incident) and 108 subjects with benign nodules. The predictive capability of baseline cfDNA to differentiate malignant and benign nodules was compared to that of Lung-RADS classification and Brock score at initial LDCT (iLDCT). Subjects with prevalent LC showed both well-discriminating radiological characteristics of the malignant nodule (16 of 17 were classified as Lung-RADS 4) and markedly increased cfDNA (mean 18.8 ng/mL). The mean diameters and Brock scores of malignant nodules at iLDCT in subjects who were diagnosed with incident LC were not different from those of benign nodules. However, 75% (9/12) of subjects with incident LC showed a baseline cfDNA ≥ 3.15 ng/mL, compared to 34% (37/108) of subjects with benign nodules (p = 0.006). Moreover, baseline cfDNA was correlated (p = 0.001) with tumor growth, measured with volume doubling time. In conclusion, increased baseline cfDNA may help to differentiate subjects with malignant and benign nodules at LDCT. Full article
(This article belongs to the Special Issue Predictive Biomarkers for Lung Cancer)
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10 pages, 364 KiB  
Article
The Clinical Value of Pre-Diagnostic Thrombocytosis for the Detection of Lung Cancer in Primary Care
by Melissa Barlow, Willie Hamilton and Sarah E. R. Bailey
Cancers 2024, 16(6), 1154; https://doi.org/10.3390/cancers16061154 - 14 Mar 2024
Viewed by 1308
Abstract
Thrombocytosis is a risk marker for lung cancer in primary care. We investigated whether thrombocytosis presents pre-diagnostically for all the histological subtypes of lung cancer and its association with the stage at diagnosis. A matched cohort study used English electronic primary care data [...] Read more.
Thrombocytosis is a risk marker for lung cancer in primary care. We investigated whether thrombocytosis presents pre-diagnostically for all the histological subtypes of lung cancer and its association with the stage at diagnosis. A matched cohort study used English electronic primary care data linked to the national cancer registry. Patients diagnosed with lung cancer aged ≥40 years with no prior history of malignancy were matched by age, sex, and general practice to five controls without lung cancer. Multivariable logistic regression models quantified the incidence of pre-diagnostic thrombocytosis and advanced-stage diagnoses, adjusting for COPD diagnosis, smoking status, and anti-platelet drug prescriptions. A total of 9504 cases were matched to 45,647 controls, consisting of 3260 (34%) adenocarcinomas (ADC), 2020 (21%) squamous cell carcinomas (SCC), 70 (<1%) large-cell carcinomas (LCC), and 1089 (12%) small-cell lung cancers (SCLC). The patients with lung cancer were 8.9 (95% CI 8.0–9.9) times more likely to exhibit pre-diagnostic thrombocytosis than the controls. The odds ratios were highest for the comparison between SCC and ADC (1.8, 95% CI 1.5–2.1). Thrombocytosis is associated with advanced-stage ADC and SCC but presented equally for early- and advanced-stage SCLC. Pre-diagnostic thrombocytosis may aid in the detection of all the histological subtypes in primary care. Full article
(This article belongs to the Special Issue Predictive Biomarkers for Lung Cancer)
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37 pages, 2029 KiB  
Systematic Review
Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review
by Juan Carlos Restrepo, Darly Martínez Guevara, Andrés Pareja López, John Fernando Montenegro Palacios and Yamil Liscano
Cancers 2024, 16(13), 2338; https://doi.org/10.3390/cancers16132338 - 26 Jun 2024
Cited by 1 | Viewed by 4145
Abstract
Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers—circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood [...] Read more.
Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers—circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood tumor mutational burden (bTMB)—enhanced by next-generation sequencing (NGS) to improve the diagnostic accuracy, prognostic evaluation, and treatment strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients from 2020 to 2024, the review highlights how biomarkers like ctDNA and PD-L1 expression critically inform the selection of personalized therapies, particularly beneficial in the advanced stages of NSCLC. These biomarkers are critical for prognostic assessments and in dynamically adapting treatment plans, where high PD-L1 expression and specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide the use of targeted therapies and immunotherapies. The findings recommend integrating these biomarkers into standardized clinical pathways to maximize their potential in enhancing the treatment precision, ultimately fostering significant advancements in oncology and improving patient outcomes and quality of life. This review substantiates the prognostic and predictive value of these biomarkers and emphasizes the need for ongoing innovation in biomarker research. Full article
(This article belongs to the Special Issue Predictive Biomarkers for Lung Cancer)
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18 pages, 2408 KiB  
Systematic Review
Methylated Cell-Free Tumor DNA in Sputum as a Tool for Diagnosing Lung Cancer—A Systematic Review and Meta-Analysis
by Sara Witting Christensen Wen, Morten Borg, Signe Timm, Torben Frøstrup Hansen, Ole Hilberg and Rikke Fredslund Andersen
Cancers 2024, 16(3), 506; https://doi.org/10.3390/cancers16030506 - 24 Jan 2024
Viewed by 1843
Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. Early diagnosis is pivotal for the prognosis. There is a notable overlap between lung cancer and chronic bronchitis, and the potential use of methylated tumor DNA in sputum as a biomarker for lung [...] Read more.
Lung cancer is the leading cause of cancer-related mortality worldwide. Early diagnosis is pivotal for the prognosis. There is a notable overlap between lung cancer and chronic bronchitis, and the potential use of methylated tumor DNA in sputum as a biomarker for lung cancer detection is appealing. This systematic review and meta-analysis followed the PRISMA 2020 statement. A comprehensive search was conducted in Embase, Medline, Web of Science, and the Cochrane Library, using these search strings: Lung cancer, sputum, and methylated tumor DNA. A total of 15 studies met the eligibility criteria. Studies predominantly utilized a case–control design, with sensitivity ranging from 10 to 93% and specificity from 8 to 100%. A meta-analysis of all genes across studies resulted in a summary sensitivity of 54.3% (95% CI 49.4–59.2%) and specificity of 79.7% (95% CI 75.0–83.7%). Notably, two less explored genes (TAC1, SOX17) demonstrated sensitivity levels surpassing 85%. The study’s findings highlight substantial variations in the sensitivity and specificity of methylated tumor DNA in sputum for lung cancer detection. Challenges in reproducibility could stem from differences in tumor site, sample acquisition, extraction methods, and methylation measurement techniques. This meta-analysis provides a foundation for prioritizing high-performing genes, calling for a standardization and refinement of methodologies before potential application in clinical trials. Full article
(This article belongs to the Special Issue Predictive Biomarkers for Lung Cancer)
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