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Biomarkers and Lung Cancer: Clinical Application
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Biomarkers and Lung Cancer: Clinical Application

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Respiratory Medicine".

Deadline for manuscript submissions: 30 October 2025 | Viewed by 4892

Special Issue Editor

Dr. Roberto Gasparri

E-Mail Website
Guest Editor
Department of Thoracic Surgery, European Institute of Oncology, Via Giuseppe Ripamonti 435, 20141 Milan, Italy
Interests: lung cancer; thoracic surgery; thoracic diseases; early diagnosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lung cancer is the leading cause of cancer-related mortality worldwide. The five-year survival rate is strongly associated with late diagnosis (23% for stage III–IV vs. 67% for the early stages).

Screening programs based on low-dose computed tomography (LD-CT) determined a 20% reduction in lung cancer mortality. However, it is not very suitable as a screening test for the mass population due to its high costs, radiation, and false positive rate. Thus, early diagnosis is essential for its therapeutic and prognostic implications. In this scenario, the absence of a non-invasive and inexpensive screening tool is the main issue for the population, particularly for high-risk subjects. Consequently, the discovery of lung cancer biomarkers in body fluids such as blood, urine, stool, saliva, sputum and breath could play a key role in the diagnosis, prognosis and treatment of lung cancer.

The goal of this Special Issue is to share new knowledge about the latest biomolecules and techniques available for minimally invasive screening of lung cancer as well as the critical limitations that require future improvement in order to upgrade the diagnosis, prognosis and treatment of lung cancer patients.

We will include clinically oriented research papers and reviews, with a strong focus on the topics of early diagnosis of lung cancer and biomarkers.

We hope this Special Issue will be of interest to you, and we look forward to receiving your contributions.

Dr. Roberto Gasparri
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. Journal of Clinical Medicine 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 2600 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

  • lung cancer
  • early diagnosis
  • prognosis
  • biomarkers
  • body fluids
  • liquid biopsy

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Published Papers (5 papers)

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Research

14 pages, 624 KiB  
Article
Polygenic Risk Score Is Associated with Developing and Dying from Lung Cancer in the National Lung Screening Trial
by Robert P. Young, Raewyn J Scott, Tom Callender, Fenghai Duan, Paul Billings, Denise R. Aberle and Greg D. Gamble
J. Clin. Med. 2025, 14(9), 3110; https://doi.org/10.3390/jcm14093110 - 30 Apr 2025
Viewed by 249
Abstract
Background: Epidemiological studies suggest lung cancer results from the combined effects of smoking and genetic susceptibility. The clinical application of polygenic risk scores (PRSs), derived from combining the results from multiple germline genetic variants, have not yet been explored in a lung cancer [...] Read more.
Background: Epidemiological studies suggest lung cancer results from the combined effects of smoking and genetic susceptibility. The clinical application of polygenic risk scores (PRSs), derived from combining the results from multiple germline genetic variants, have not yet been explored in a lung cancer screening cohort. Methods: This was a post hoc analysis of 9191 non-Hispanic white subjects from the National Lung Screening Trial (NLST), a sub-study of high-risk smokers randomised to annual computed tomography (CT) or chest X-ray (CXR) and followed for 6.4 years (mean). This study’s primary aim was to examine the relationship between a composite polygenic risk score (PRS) calculated from 12 validated risk genotypes and developing or dying from lung cancer during screening. Validation was undertaken in the UK Biobank of unscreened ever-smokers (N = 167,796) followed for 10 years (median). Results: In this prospective study, we found our PRS correlated with lung cancer incidence (p < 0.0001) and mortality (p = 0.004). In an adjusted multivariable logistic regression analysis, PRS was independently associated with lung cancer death (p = 0.0027). Screening participants with intermediate and high PRS scores had a higher lung cancer mortality, relative to those with a low PRS score (rate ratios = 1.73 (95%CI 1.14–2.64, p = 0.010) and 1.89 (95%CI 1.28–2.78, p = 0.009), respectively). This was despite comparable baseline demographics (including lung function) and comparable lung cancer characteristics. The PRS’s association with lung cancer mortality was validated in an unscreened cohort from the UK Biobank (p = 0.002). Conclusions: In this biomarker-based cohort study, an elevated PRS was independently associated with dying from lung cancer in both screening and non-screening cohorts. Full article
(This article belongs to the Special Issue Biomarkers and Lung Cancer: Clinical Application)
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21 pages, 1398 KiB  
Article
The Impact of the Histologic Types of Lung Cancer on CBC-Derived Inflammatory Markers—Current Knowledge and Future Perspectives
by Claudia Raluca Mariean, Oana Mirela Tiucă, Alexandru Mariean, Tiberiu-Bogdan Szekely, Raluca Niculescu, Adrian Horatiu Sabau, Cristina Flavia Al-Akel and Ovidiu Simion Cotoi
J. Clin. Med. 2025, 14(9), 3038; https://doi.org/10.3390/jcm14093038 - 28 Apr 2025
Viewed by 462
Abstract
Background/Objectives: The analysis of the complete blood count (CBC)-derived inflammatory indexes across different histological subtypes of lung cancer supports the early detection of tumor-induced inflammation and has a good predictive value for severity in cancer patients. The main objective of this article [...] Read more.
Background/Objectives: The analysis of the complete blood count (CBC)-derived inflammatory indexes across different histological subtypes of lung cancer supports the early detection of tumor-induced inflammation and has a good predictive value for severity in cancer patients. The main objective of this article was to assess the variations in CBC-derived inflammatory markers across different histologic subtypes of lung cancer, with the final goal of identifying specific predictors of severity for each histologic subtype of lung cancer. Methods: We conducted a retrospective descriptive study that included 202 patients diagnosed with lung carcinoma at the Clinical County Hospital Mureș. The analyzed parameters were as follows: the histological type, the stage of the tumor, patients’ general data, and associated comorbidities. In addition, nine CBC-derived inflammatory indexes, like the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI), were analyzed as predictors of severity and correlated with histologic findings. Results: The predictors of severity differed across the histologic subtypes. SIRI, d-NLR, and age were predictors of severity in adenocarcinoma patients, while the d-NLR, ENR, leukocyte, and neutrophil count predicted severity in squamous cell carcinoma. For SCLC patients, AISI, SIRI, SII, d-NLR, EMR, ENR, MLR, leukocyte count, lymphocyte count, neutrophil count, platelets count, COPD, smoking, and male gender were predictors for severity. Conclusions: Understanding the complexity and variations in the inflammatory response across different histologic types of lung cancer can personalize treatment regimens and target specific abnormal cellular lines, thus improving the outcome of this highly deadly condition. Full article
(This article belongs to the Special Issue Biomarkers and Lung Cancer: Clinical Application)
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15 pages, 1167 KiB  
Article
Association Between Cutaneous Immune-Related Adverse Events and Efficacy of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer
by José Miguel Jurado, Vanesa Gutiérrez, Alexandra Cantero, Miguel-Ángel Berciano-Guerrero, Airam Padilla, Elisabet Pérez-Ruiz, Álvaro Montesa, Francisco Carabantes and Manuel Cobo
J. Clin. Med. 2025, 14(7), 2499; https://doi.org/10.3390/jcm14072499 - 6 Apr 2025
Cited by 1 | Viewed by 449
Abstract
Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed the treatment of patients with non-small cell lung cancer (NSCLC). Numerous studies have suggested that immune-related adverse events (irAEs) are associated with ICI efficacy and can affect any organ system. This study aims to evaluate [...] Read more.
Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed the treatment of patients with non-small cell lung cancer (NSCLC). Numerous studies have suggested that immune-related adverse events (irAEs) are associated with ICI efficacy and can affect any organ system. This study aims to evaluate the prognostic significance of cutaneous IrAEs (cirAEs) and their impact on the effectiveness of PD-1/PD-L1 inhibitors in real-world NSCLC data. Methods: We retrospectively collected NSCLC patients treated with ICI as first- or second-line therapy between 2015 and 2022 at a single institution. We evaluated the association between cirAEs and treatment efficacy, measured by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Kaplan–Meier survival curves were generated, and log-rank tests were used for significance testing. Multivariable analysis was performed using Cox proportional hazards regression models. Results: A total of 510 patients were included in the analysis, with a median age of 62 years (range 34–85), and 75% of patients were males. CirAEs of any grade were observed in 139 patients (27.3%). Among patients assessed for efficacy, the ORR was significantly higher in those with cirAEs compared to those without (54.3% vs. 29.9%, p = 0.0001). At a median follow-up of 48 months, PFS (14.6 vs. 4.7 months, p = 0.0001) and OS (29 vs. 9.2 months, p = 0.0001) were significantly improved in patients with cirAEs. Patients with grade 1–2 cirAEs showed even greater survival benefits (PFS: median 14.9 months, p = 0.003; OS: median 30 months, p = 0.001). Multivariable analysis confirmed that the development of any cirAE was independently associated with significantly improved OS (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.44–0.80, p = 0.0001). The presence of multisystem ≥ 2 SOC irAEs, including cirAE, was strongly correlated with the greatest benefit from ICIs HR:0.51 (95% CI 0.35–0.74), p = 0.001. Conclusions: This study supports that cirAEs could be used as a potential marker of ICI efficacy in NSCLC. The development of multisystem cirAEs may prognose the greatest benefit of treatment. Full article
(This article belongs to the Special Issue Biomarkers and Lung Cancer: Clinical Application)
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11 pages, 2550 KiB  
Article
Circulating RKIP and pRKIP in Early-Stage Lung Cancer: Results from a Pilot Study
by Roberto Gasparri, Massimo Papale, Angela Sabalic, Valeria Catalano, Annamaria Deleonardis, Federica De Luca, Elena Ranieri and Lorenzo Spaggiari
J. Clin. Med. 2024, 13(19), 5830; https://doi.org/10.3390/jcm13195830 - 29 Sep 2024
Cited by 1 | Viewed by 1872
Abstract
Background: Lung cancer (LC) is the leading cause of cancer-related deaths. Although low-dose computed tomography (LD-CT) reduces mortality, its clinical use is limited by cost, radiation, and false positives. Therefore, there is an urgent need for non-invasive and cost-effective biomarkers. The Raf Kinase [...] Read more.
Background: Lung cancer (LC) is the leading cause of cancer-related deaths. Although low-dose computed tomography (LD-CT) reduces mortality, its clinical use is limited by cost, radiation, and false positives. Therefore, there is an urgent need for non-invasive and cost-effective biomarkers. The Raf Kinase Inhibitor Protein (RKIP) plays a crucial role in cancer development and progression and may also contribute to regulating the tumor–immune system axis. This protein has recently been described in biological fluids. Therefore, we conducted a pilot case–control study to assess RKIP and phosphorylated RKIP (pRKIP) levels in the urine and blood of LC patients. Methods: A novel enzyme linked immunosorbent assay (ELISA) assay was used to measure RKIP and pRKIP levels in urine and blood samples of two cohorts of LC patients and healthy controls (HSs). Furthermore, the biomarkers levels were correlated with tumor characteristics. Results: Serum, but not urine, levels of RKIP were significantly elevated in LC patients, distinguishing them from low- and high-risk healthy subjects with 93% and 74% accuracy, respectively. The RKIP/pRKIP ratio (RpR score) showed an accuracy of 90% and 79% in distinguishing LC patients from HS and HR-HS, respectively. Additionally, the RpR score correlated better with dimension, stage, and lymph node involvement in the tumor group. Conclusions: The serum RKIP and pRKIP profile may be a promising novel biomarker for early-stage LC. Full article
(This article belongs to the Special Issue Biomarkers and Lung Cancer: Clinical Application)
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21 pages, 2835 KiB  
Article
Toll-like Receptors: Key Players in Squamous Cell Carcinoma Progression
by Jolanta Smok-Kalwat, Paulina Mertowska, Sebastian Mertowski, Stanisław Góźdź and Ewelina Grywalska
J. Clin. Med. 2024, 13(15), 4531; https://doi.org/10.3390/jcm13154531 - 2 Aug 2024
Cited by 1 | Viewed by 1256
Abstract
Background/Objectives Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer, characterized by diverse molecular pathways and variable clinical outcomes. This study focused on assessing the levels of TLR-2, TLR-3, TLR-4, TLR-7, TLR-8, and TLR-9 on peripheral blood lymphocytes [...] Read more.
Background/Objectives Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer, characterized by diverse molecular pathways and variable clinical outcomes. This study focused on assessing the levels of TLR-2, TLR-3, TLR-4, TLR-7, TLR-8, and TLR-9 on peripheral blood lymphocytes in patients with newly diagnosed SCC compared to a group of healthy controls, in the context of disease development and patient survival, conducted over three years. The study aimed to investigate the differences in TLR expression between SCC patients and healthy people and to understand their role in the development of the disease and patient survival over three years. Methods: The study included the assessment of TLR-2, TLR-3, TLR-4, TLR-7, TLR-8, and TLR-9 levels on peripheral blood lymphocytes in patients with newly diagnosed SCC and in the control group. The expression of TLRs was measured using flow cytometry, and the soluble forms of the tested TLRs were measured using enzyme-linked immunosorbent assays. All the analyses were conducted over a three-year period from the time patients were recruited to the study. The obtained test results were statistically analyzed. Results: Results showed statistically significant differences in TLR expression between the groups, with higher TLR levels correlating with an advanced stage of disease and poorer survival rates. This suggests that the deregulation of TLR levels may be involved in promoting tumor development and influencing its microenvironment. Conclusions: The research, conducted over three years, indicates the need for further research on the role of TLRs in SCC, including their potential use as therapeutic targets and biomarkers. This may help to increase the effectiveness of standard treatments and improve clinical outcomes in patients with SCC. Full article
(This article belongs to the Special Issue Biomarkers and Lung Cancer: Clinical Application)
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