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Novel Biomarkers in Lung Cancer and Chronic Lung Diseases
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Novel Biomarkers in Lung Cancer and Chronic Lung Diseases

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 15606

Special Issue Editor

Dr. In-Jae Oh

E-Mail Website
Guest Editor
Department of Internal Medicine, Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Jeonnam, Republic of Korea
Interests: lung cancer; chronic obstructive pulmonary disease; interstitial lung disease; smoking
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The new approach to cancer treatment, called personalized medicine, is made possible by the discovery of biomarkers. Biomarkers are molecular characteristics of a tumor that can be used to help make decisions about treatment. Through the recognition of novel biomarkers, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, it has been possible to identify subsets of patients who benefit from targeted therapies. The success of targeted anticancer therapies and new immunotherapeutic approaches has created a new paradigm of personalized therapy and has also led to the accelerated development of new drugs for lung cancer treatment.
In addition, chronic lung diseases such as chronic obstructive pulmonary disease, interstitial lung disease, tuberculosis, and other smoking-related diseases are major causes of morbidity and mortality worldwide and result in an economic and social burden that is both substantial and increasing. To improve the prognosis of chronic lung disease, a customized approach based on novel biomarkers is also needed.
Therefore, all the research and advances about novel biomarkers that are associated with lung cancer and chronic lung diseases are welcome in this Special Issue. Original articles, comprehensive and critical reviews and even letters are of utmost interest, given the expansive interest of this area.

Dr. In-Jae Oh
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
  • Biomarker
  • Chronic obstructive pulmonary disease
  • Interstitial lung disease
  • Tuberculosis
  • Smoking

Published Papers (7 papers)

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Editorial

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3 pages, 203 KiB  
Editorial
Novel Biomarkers in Lung Cancer and Chronic Lung Diseases: From the Systematic Perspective of Yin–Yang Balance
by Mi-Kyung Jeong, Jaemoo Chun and In-Jae Oh
J. Clin. Med. 2022, 11(15), 4275; https://doi.org/10.3390/jcm11154275 - 22 Jul 2022
Viewed by 977
Abstract
New approaches to personalized medicine are made possible by the discovery of biomarkers [...] Full article
(This article belongs to the Special Issue Novel Biomarkers in Lung Cancer and Chronic Lung Diseases)

Research

Jump to: Editorial

11 pages, 1619 KiB  
Article
CDCP1 Expression Is a Potential Biomarker of Poor Prognosis in Resected Stage I Non-Small-Cell Lung Cancer
by Yunha Nam, Chang-Min Choi, Young Soo Park, HyunA Jung, Hee Sang Hwang, Jae Cheol Lee, Jung Wook Lee, Jung Eun Lee, Jung Hee Kang, Byung Hun Jung and Wonjun Ji
J. Clin. Med. 2022, 11(2), 341; https://doi.org/10.3390/jcm11020341 - 11 Jan 2022
Cited by 7 | Viewed by 1715
Abstract
Background: Although early-stage lung cancer has increased owing to the introduction of screening programs, high recurrence rate remains a critical concern. We aimed to explore biomarkers related to the prognosis of surgically resected non-small-cell lung cancer (NSCLC). Methods: In this retrospective study, we [...] Read more.
Background: Although early-stage lung cancer has increased owing to the introduction of screening programs, high recurrence rate remains a critical concern. We aimed to explore biomarkers related to the prognosis of surgically resected non-small-cell lung cancer (NSCLC). Methods: In this retrospective study, we collected medical records of patients with NSCLC and matched tissue microarray blocks from surgical specimens. Semiquantitative immunohistochemistry was performed for measuring the expression level of fibroblast activation protein-alpha (FAP-α), Jagged-1 (JAG1), and CUB-domain-containing protein 1 (CDCP1). Results: A total of 453 patients who underwent complete resection between January 2011 and February 2012 were enrolled; 55.2% patients had stage I NSCLC, and 31.1% presented squamous cell carcinoma. Disease stage was a significant risk factor for recurrence and death, and age ≥ 65 years and male sex were associated with poor overall survival. FAP-a and JaG1 were not related to survivals, while CDCP1-expressing patients exhibited poor disease-free and overall survival. Moreover, CDCP1 expression in stage I NSCLC was significantly associated with recurrence. Conclusions: Old age, male sex, and high pathological stage were poor prognostic factors in patients with NSCLC who underwent surgical resection. Furthermore, CDCP1 expression could serve as a biomarker for poor prognosis in stage I NSCLC. Full article
(This article belongs to the Special Issue Novel Biomarkers in Lung Cancer and Chronic Lung Diseases)
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11 pages, 1632 KiB  
Article
Soluble ST2 and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease—A 10-Year Cohort Study
by Matthias H. Urban, Stefan Stojkovic, Svitlana Demyanets, Christian Hengstenberg, Arschang Valipour, Johann Wojta and Otto C. Burghuber
J. Clin. Med. 2022, 11(1), 56; https://doi.org/10.3390/jcm11010056 - 23 Dec 2021
Cited by 9 | Viewed by 2542
Abstract
Chronic obstructive pulmonary disease (COPD) is an inflammatory condition with constantly increasing mortality rates. Interleukin (IL)-33 and its decoy receptor, soluble suppression of tumorigenicity 2 (sST2), play a central role in the inflammatory response during infection. sST2 was suggested as a factor in [...] Read more.
Chronic obstructive pulmonary disease (COPD) is an inflammatory condition with constantly increasing mortality rates. Interleukin (IL)-33 and its decoy receptor, soluble suppression of tumorigenicity 2 (sST2), play a central role in the inflammatory response during infection. sST2 was suggested as a factor in the pathogenesis of COPD and emerged as a predictor of mortality in other non-communicable diseases. The role of sST2 as a predictor of mortality remains unclear in COPD yet. In this cohort study, we measured circulating concentrations of IL-33 and sST2 in the serum of patients with stable COPD (n = 59), patients with acute exacerbation of COPD (n = 29) and smoking (n = 20) and non-smoking controls (n = 20), using commercially available ELISAs, and investigated the prognostic role of sST2 in stable COPD. sST2 levels were significantly higher in COPD patients and smokers compared with non-smoking controls. We identified systolic blood pressure, forced expiratory volume in 1 s (FEV1% predicted), neutrophil count, lactate dehydrogenase and pack-years index as independent predictors of sST2 levels. During a median follow-up time of 10.6 years, 28 patients (47.5%) died. sST2 was an independent predictor of all-cause mortality in patients with COPD with a hazard ratio of 2.9 (95% CI 1.1–8.4, p = 0.035) per one standard deviation after adjustment for age, sex, pack-years, FEV1% predicted and C-reactive protein (CRP). sST2 concentrations are associated with severity of disease and long-term outcome in patients with COPD. Full article
(This article belongs to the Special Issue Novel Biomarkers in Lung Cancer and Chronic Lung Diseases)
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13 pages, 1262 KiB  
Article
GAP Score and CA-153 Associated with One-Year Mortality in Anti-MDA-5 Antibody-Positive Patients: A Real-World Experience
by Chih-Wei Tseng, Kao-Lun Wang, Pin-Kuei Fu, Cheng-Yi Huang, Tsu-Yi Hsieh, Chia-Wei Hsieh, Kuo-Lung Lai, Wei-Ting Hung, Ching-Tsai Lin, Kuo-Tung Tang, Yi-Ming Chen, Wen-Nan Huang and Yi-Hsing Chen
J. Clin. Med. 2021, 10(22), 5241; https://doi.org/10.3390/jcm10225241 - 11 Nov 2021
Cited by 9 | Viewed by 2453
Abstract
Background. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. Methods. We retrospectively [...] Read more.
Background. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. Methods. We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up. Results. A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality. Conclusions. Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management. Full article
(This article belongs to the Special Issue Novel Biomarkers in Lung Cancer and Chronic Lung Diseases)
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8 pages, 393 KiB  
Article
Endothelial Progenitor Cells as a Potential Biomarker in Interstitial Lung Disease Associated with Rheumatoid Arthritis
by Verónica Pulito-Cueto, Sara Remuzgo-Martínez, Fernanda Genre, Víctor M. Mora-Cuesta, David Iturbe-Fernández, Sonia Fernández-Rozas, Belén Atienza-Mateo, Leticia Lera-Gómez, Pilar Alonso-Lecue, Javier Rodríguez-Carrio, Diana Prieto-Peña, Virginia Portilla, Ricardo Blanco, Alfonso Corrales, Oreste Gualillo, José M. Cifrián, Raquel López-Mejías and Miguel A. González-Gay
J. Clin. Med. 2020, 9(12), 4098; https://doi.org/10.3390/jcm9124098 - 18 Dec 2020
Cited by 15 | Viewed by 2277
Abstract
Interstitial lung disease (ILD) increases morbidity and mortality in patients with rheumatoid arthritis (RA). Although the pathogenesis of ILD associated with RA (RA-ILD+) remains poorly defined, vascular tissue is crucial in lung physiology. In this context, endothelial progenitor cells (EPC) are [...] Read more.
Interstitial lung disease (ILD) increases morbidity and mortality in patients with rheumatoid arthritis (RA). Although the pathogenesis of ILD associated with RA (RA-ILD+) remains poorly defined, vascular tissue is crucial in lung physiology. In this context, endothelial progenitor cells (EPC) are involved in endothelial tissue repair. However, little is known about their implication in RA-ILD+. Accordingly, we aimed to investigate the potential role of EPC related to endothelial damage in RA-ILD+. EPC quantification in peripheral blood from 80 individuals (20 RA-ILD+ patients, 25 RA-ILD− patients, 21 idiopathic pulmonary fibrosis (IPF) patients, and 14 healthy controls) was performed by flow cytometry. EPC were considered as CD34+, CD45low, CD309+ and CD133+. A significant increase in EPC frequency in RA-ILD+ patients, as well as in RA-ILD− and IPF patients, was found when compared with controls (p < 0.001, p = 0.02 and p < 0.001, respectively). RA-ILD+ patients exhibited a higher EPC frequency than the RA-ILD− ones (p = 0.003), but lower than IPF patients (p < 0.001). Our results suggest that EPC increase may represent a reparative compensatory mechanism in patients with RA-ILD+. The degree of EPC frequency may help to identify the presence of ILD in RA patients and to discriminate RA-ILD+ from IPF. Full article
(This article belongs to the Special Issue Novel Biomarkers in Lung Cancer and Chronic Lung Diseases)
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14 pages, 1039 KiB  
Article
Glutathione Peroxidase 3 as a Biomarker of Recurrence after Lung Cancer Surgery
by Bo Gun Kho, Ha-Young Park, Hyun-Joo Cho, Cheol Kyu Park, Young-Chul Kim, Ju-Sik Yun, Sang-Yun Song, Kook-Joo Na, Yoo-Duk Choi, Seung-Won Lee and In-Jae Oh
J. Clin. Med. 2020, 9(12), 3801; https://doi.org/10.3390/jcm9123801 - 24 Nov 2020
Cited by 5 | Viewed by 1570
Abstract
We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete [...] Read more.
We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete resection cases in 2013. GPx3 levels were measured by enzyme-linked immunosorbent assay. Statistical tests including t-tests and Cox proportional hazard regression analyses were performed. Totally, 135 patients were enrolled, and 39 (28.9%) showed relapse during the median follow-up period (63.60 months; range, 0.167–81.867). The mean GPx3 change was significantly higher in the recurrence group at 6 months (0.32 ± 0.38 vs. 0.15 ± 0.29, p = 0.016) and 12 months (0.40 ± 0.37 vs. 0.13 ± 0.28, p = 0.001). The high GPx3 change group showed significantly higher 60-months recurrence rates than the low group (48.1% vs. 25.2% at 3 months, p = 0.005; 54.5% vs. 28.9% at 6 months, p = 0.018; 38.3% vs. 18.3% at 12 months, p = 0.035). High GPx3 change at 3 months were independent risk factors of recurrence (hazard ratio (HR) 3.318, 95% confidence interval (CI), 1.582–6.960, p = 0.002) and survival (HR 3.150, 95% CI, 1.301–7.628, p = 0.011). Therefore, serum GPx3 changes after surgery may be useful predictive biomarkers for recurrence in lung cancer. Larger-scale validation studies are warranted to confirm these findings. Full article
(This article belongs to the Special Issue Novel Biomarkers in Lung Cancer and Chronic Lung Diseases)
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11 pages, 3796 KiB  
Article
Scores of Health-Related Quality of Life Questionnaire Worsen Consistently in Patients of COPD: Estimating Disease Progression over 30 Years by SReFT with Individual Data Collected in SUMMIT Trial
by Shinya Kawamatsu, Ryota Jin, Shogo Araki, Hideki Yoshioka, Hiromi Sato, Yasunori Sato and Akihiro Hisaka
J. Clin. Med. 2020, 9(8), 2676; https://doi.org/10.3390/jcm9082676 - 18 Aug 2020
Cited by 2 | Viewed by 3355
Abstract
The aim of this study was to elucidate the lifelong disease progression of chronic obstructive pulmonary disease (COPD) with biomarker changes and identify their influencing factors, by utilizing a new analysis method, Statistical Restoration of Fragmented Time-course (SReFT). Individual patient data (n [...] Read more.
The aim of this study was to elucidate the lifelong disease progression of chronic obstructive pulmonary disease (COPD) with biomarker changes and identify their influencing factors, by utilizing a new analysis method, Statistical Restoration of Fragmented Time-course (SReFT). Individual patient data (n = 1025) participating in the Study to Understand Mortality and MorbidITy (SUMMIT, NCT01313676), which was collected within the observational period of 4 years, were analyzed. The SReFT analysis suggested that scores of St. George’s Respiratory Questionnaire and COPD assessment test, representative scores of the health-related quality of life (HRQOL) questionnaire, increased consistently for 30 years of disease progression, which was not detected by conventional analysis with a linear mixed effect model. It was estimated by the SReFT analysis that normalized forced expiratory volume in one second for age, sex, and body size (%FEV1) reduced for the initial 10 years from the onset of the disease but thereafter remained constant. The analysis of HRQOL scores and lung functions suggested that smoking cessation slowed COPD progression by approximately half and that exacerbation accelerated it considerably. In conclusion, this retrospective study utilizing SReFT elucidated the progression of COPD over 30 years and associated quantitative changes in the HRQOL scores and lung functions. Full article
(This article belongs to the Special Issue Novel Biomarkers in Lung Cancer and Chronic Lung Diseases)
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