A novel combined score of biomarkers in sputum may be an indicator for lung cancer: A pilot study
Introduction
Lung cancer is one of the leading causes of cancer-related death worldwide [1]. Despite significant advances in surgical techniques and medical targeted treatment and immunotherapy, the 5- year survival rate in patients with lung cancer remains poor with an overall 5-year survival rate of 4–17% [2] The extremely poor prognosis associated with lung cancer is related to the difficulty of early diagnosis and high incidence of regional or distant metastasis and the occurrence of treatment resistance.
While age, family history of lung cancer and occupational exposures are factors that may lead to lung cancer, cigarette smoking is the main risk factor. Recent results from the National Lung Screening Trial have shown that annual screening of high-risk smokers with low-dose computed tomography of the chest can reduce lung cancer mortality by 20.0% [3], however one major caveat of this important study was a very high incidence of false positive results, which may lead to high screening costs and unnecessary invasive procedures, if such a screening program is applied. Therefore there is an urgent and growing need to develop and validate biomarkers that can both help identify those smokers at highest risk who are most likely to benefit from screening.
Since autophagy, inflammation and angiogenesis are an integral part of lung cancer pathogenesis and propagation [[4], [5], [6], [7], [8], [9]], we aim to examine a combination of markers of these processes as an indicator for lung cancer, in the novel milieu of induced sputum. Induced sputum was chosen as a non-invasive method to sample the immune cells and cytokines in the lung environment. These markers cannot be sample or not accurate in blood or breathe condensate.
Section snippets
Study population
The study population included 60 patients (31 with lung cancer and 29 with chronic obstructive pulmonary disease [COPD]) recruited from the outpatient clinic of the institute of pulmonary diseases in the Tel-Aviv Sourasky Medical Center, between Feb. 2013 and Jan. 2016. Thirty healthy individuals comprised the control group. Each participant had undergone a comprehensive medical evaluation, spirometry and sputum induction. Patients with comorbidities such as known cardiovascular disease, other
Discussion
This pilot study evaluated potential biomarkers in the induced sputum of healthy controls and patients with COPD or lung cancer. The main finding was the design of a new score that combined five different biomarkers for predicting the presence of lung cancer.
Induced sputum is recognized as a very useful sampling method for both research and clinical use aiding both the diagnosis and monitoring of disease status [12]. A great advantage of the technique is that it enables sampling of the airways
Conclusions
Collectively, the data presented in this report suggest that lung cancer induces autophagy as well as angiogenesis and leukocyte adhesion in immune cells of the lungs and airways. Furthermore, our findings are the first to reveal a potential, novel and noninvasive way to identify patients with lung cancer by using a combination of biomarkers in induced sputum. Recognizing the patients who need further evaluation and close follow-up is an unmet need in the era of lung cancer screening programs.
Formatting of funding sources
This research did not receive any specific grants from funding agencies in the public, commercial or not-for-profit sectors.
Declaration of interest
None.
Acknowledgments
Amir Bar-Shai takes responsibility for (is the guarantor of) the content of the manuscript, including the data and their analysis.
All authors confirm that the work is original and that they meet the criteria for authorship, including acceptance of responsibility for the scientific content of the manuscript.
Esther Eshkol is thanked for editorial assistance.
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