Validation and delivery of infrared spectral biomarkers of lung cancer risk

The project found that differences could be detected between cheek (or ‘buccal’) cells of patients with a lung cancer compared to those without when analysed with infrared light. Further expansion of this work in a larger population created a classifier to identify individuals with lung cancer from those without. It is hoped that future work could further investigate the potential of this technology to establish a non-invasive screening test that could help improve the early diagnosis of lung cancer.

Background

Lung cancer is generally asymptomatic until late-stage development where it is often incurable. Currently, there is no form of general population screening that would identify people with lung cancer before exhibiting any symptoms.

Previous work by the Janes lab, funded by Roy Castle Lung Cancer Foundation, suggested it may be possible to detect lung cancer from biochemical changes occurring in the cells of the mouth or lining of the cheek (these are called ‘buccal cells’).

In this research, swabs containing cells from healthy people and those with lung cancer were collected and processed, and the absorbance of infrared light by these samples was analysed. Different biochemical profiles were observed in mouth (buccal) cells of healthy vs. cancer patient samples.

130 patients were recruited to the study. Samples were analysed with FTIR spectroscopy using two different light sources. The first is a very powerful light source (synchrotron), only found at one facility in the UK; the second is a more widely available conventional light source that can be used in a normal laboratory setting.

The results, obtained with measurements from both light sources, showed that significant differences were detected in the spectral signatures of buccal cells from patients with lung cancer compared to those without. Significantly, these differences were found to be independent of smoking status.

Subsequent work identified classifiers to differentiate between individuals with lung cancer from those without the disease, based on the buccal spectral signature detected. This research has identified differences in the buccal cell spectra of patients with lung cancer compared to those without and has provided a foundation on which future work can expand, looking to develop a lung cancer screening tool using FTIR spectroscopy.

Future work could further investigate the potential of this technology to establish a non-invasive screening test that could help improve the early diagnosis of lung cancer, that would include people who have never smoked.

Prof. Sam Janes

What is the problem to be addressed?

Finding a valid and accurate way to diagnose lung cancer early.

Unlike most cancers, there has been little progress in cure rates for lung cancer over the past two decades.

Recently, screening for lung cancer has been achieved using CT scans, with some success. However, the expense of screening large numbers of people to detect a single cancer case may preclude its use in most healthcare systems.

Any method that can streamline radiological screening and potentially include the non-smoking general population, which makes up at least 20% of lung cancers will be a huge advance.

A simple biological screen to detect those at most risk would be clinically invaluable and have important health economic benefits.

Prof Sam Janes is excited about this project.

He said: ‘’Investigating infrared-spectral biomarkers – what does that mean? What we think happens when people are perhaps at risk of cancer, or even have a lung cancer, is that many cells around the body change, quite subtly.

We take a few cells from inside a person’s cheek, and we shine a special light source on these cells. What appears to happen is that the cells inside the mouth reflect light slightly differently if a person is at a high risk of having lung cancer.

So, we believe in the future that we might be able to develop this so that we could perhaps use it as quite a high through-put test; perhaps in GP surgeries, or pharmacies, testing people’s cheek cells to see if they’re at a higher risk of developing lung cancer’’.

Findings and outcomes

• A significant difference was detected between buccal spectral signature of patients with a distal lung cancer compared to those without.
• The difference detected was independent of smoking status
• 130 patients were recruited to this project in total, with repeat analysis in different cohorts, showing reproducibility of initial findings. A significant difference between groups was detected in all cohorts.
• The creation of classifiers to distinguish between individuals with lung cancer from those without.
• Further work is needed to develop these interesting findings before clinical translation.

Publications:

Impact factor	How presented (oral, poster or journal publication)	Title	Year	Authors	Journal publication name / conference venue	Status (in submission, in press or published)
n/a	Poster	Detecting lung cancer risk using infrared spectral biomarkers	2018	S Antoniou et al,	SPEC Glasgow	Presented
n/a	Poster	Identifying an infrared spectral biomarker of lung cancer risk	2018	S Antoniou et al,	CRUK York	Presented
n/a	Poster and oral presentation	Identifying an infrared spectral biomarker of lung cancer risk	2019	S Antoniou et al,	ATS Dallas	Presented

Is this RCLCF funded work (or aspects of it) being continued with new funding?

This project was conducted with Beamline Ltd and supported by the team at Diamond Light Source, who facilitated access to the synchrotron FTIR spectrometer. There is no current ongoing funding and planned continuation of this research, but our collaborators previously known as Beamline Ltd are applying for further funding to further investigate this interesting area of research.

Professor Sam Janes

Advisory boards/committee positions

• 2017- Present: CRUK Early Detection Panel 
• 2012- Present: Roy Castle Lung Cancer Foundation Grant Committee 
• 2022- Jules Thorne Medical Advisory Board

Numerous Peer review

Editing scientific publications

• Associate editor of Thorax and Chest  
• Editor and Chief The Encyclopaedia of Respiratory Medicine

Fellowship European Respiratory Society Fellow

Received prizes relating to research:

• 2021 Keynote AACR-NIH-EORTC Molecular Targets Conference
• 2021 Keynote Oncology Futures
• 2019  British Thoracic Society: The Clinical Lecture 
• 2019 American Thoracic Society: Lung Cancer Year in Review Lecture 
• 2018  Fellow of the European Respiratory Society (FERS) 
• 2018 European Respiratory Society: Year in Review Lecture 
• 2010  European Respiratory Society Thoracic Oncology Award (Euro 10,000) Awarded to the under 45 researcher of the year. Barcelona 2010 
• 2009   American Thoracic Society Best Abstract Award at San Diego 2009 
• 2003   British Thoracic Society Young Investigator of the Year, London 2003 

Dr Sophia Antoniou has been involved in both writing and peer review of scientific publications.

What degrees/professional qualifications were obtained during this RCLCF grant funding, eg MSc, PhD?

The clinical fellow, Dr Sophia Antoniou, who was supported by this RCLCF grant and who undertook this research, has obtained a PhD.

What is the grant holder/researcher doing now?

Professor Sam Janes remains dedicated to research to improve the understanding, care and treatment of lung cancer. Dr Sophia Antoniou is returning to clinical training. They are in the process of submitting the results from this project for publication.

The funding received from the RCLCF was of critical importance to this project enabling this research. The results of which have further shown potential of FTIR spectroscopy as a possible tool in early lung cancer diagnosis. It has been an important project which future research will build on.

Lead researchers: Prof Sam Janes / Dr Sophia Antoniou / Location: University College London, UCL respiratory / Type of research: early detection