BackgroundSurvival time for lung cancer is poor with over 90% of patients dying within five years of diagnosis primarily due to detection at late stage. The main objective of this study was to evaluate Fourier transform infrared spectroscopy (FTIR) as a high throughput and cost effective method for identifying biochemical changes in sputum as biomarkers for detection of lung cancer.MethodsSputum was collected from 25 lung cancer patients in the Medlung observational study and 25 healthy controls. FTIR spectra were generated from sputum cell pellets using infrared wavenumbers within the 1800 to 950 cm-1 "fingerprint" region.ResultsA panel of 92 infrared wavenumbers had absorbances significantly different between cancer and normal sputum spectra and were associated with putative changes in protein, nucleic acid and glycogen levels in tumours. Five prominent significant wavenumbers at 964 cm-1, 1024 cm-1, 1411 cm-1, 1577 cm-1 and 1656 cm-1 separated cancer spectra from normal spectra into two distinct groups using multivariate analysis (group 1: 100% cancer cases; group 2: 92% normal cases). Principal components analysis revealed that these wavenumbers were also able to distinguish lung cancer patients who had previously been diagnosed with breast cancer. No patterns of spectra groupings were associated with inflammation or other diseases of the airways.ConclusionsOur results suggest that FTIR applied to sputum might have high sensitivity and specificity in diagnosing lung cancer with potential as a non-invasive, cost-effective and high-throughput method for screening.Trial RegistrationClinicalTrials.gov: NCT00899262

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Lung cancer is the most common cancer worldwide and causes more deaths per year than any other cancer. It has a very poor 5-year survival rate of 8-16%, partly because of comorbidity preventing curative treatments but mainly because of the disease presenting with symptoms only when it is at an advanced and incurable stage. When lung cancer is detected earlier and is amenable to radical treatments such as potentially curative surgery and radical radiotherapy, 5-year survival rates are much higher (up to 67%). Therefore reliable detection of lung cancer at this earlier (usually asymptomatic) stage of disease should be an important way to improve outcomes. This review discusses the principles of screening with respect to lung cancer, concentrating mainly on the biological modalities used to detect it. The lack of impact achieved by early studies using sputum cytology (in conjunction with chest radiographs) is described, and then newer technology used to measure other biomarkers in sputum, serum, exhaled breath and bronchial mucosa to diagnose (early) lung cancer is detailed. Many techniques show promise, but debate continues about which population to screen and what is the most (cost) effective modality to use. Moreover, no single biomarker or combination of biomarkers in screening has yet been shown to reduce lung cancer mortality in large prospective randomised studies.Lung cancer is the most common cancer worldwide in terms of both incidence and mortality, with 1.3 million new cases being diagnosed each year and 1.2 million deaths, with Europe and North America having the highest incidence and prevalence rates.1 2 Compared with other common cancers such as prostate and breast cancer, lung cancer has much lower survival rates, and, despite advances in radiological tests, particularly CT and positron emission tomography scanning, surgical techniques and postoperative management, radiotherapy delivery and new chemotherapeutic agents, the long-term survival from lung cancer has remained remarkably constant and has not improved significantly over the last 20 years.3 Apart from lowering its incidence by reducing cigarette smoking, the key to improving lung cancer survival at present is to diagnose it at an earlier stage. This has led to decades of research to identify a suitable screening technique in order to reduce mortality.The objectives of this article are to describe the principles of screening and show how they are relevant to lung cancer. We will briefly discuss purely radiological attempts at screening with lowdose spiral CT (LDCT) and how simple radiology (chest radiographs (CXRs)) has been combined with sputum cytology, before describing in more detail how novel biological techniques (or biomarkers) have been tried and are still being applied in the detection of lung cancer. We will also explain some of the biological reasoning for the use of certain biomarkers and, in particular, how they are based on a better molecular understanding of lung carcinogenesis.

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