British Journal of Cancer - Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors

Molecular Diagnostics

British Journal of Cancer (2010)-103,542–551.doi:10.1038/sj.bjc.6605810 www.bjcancer.com
Published online 20 July 2010

Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors
G Peng1,2,5, M Hakim1,5, Y Y Broza1,5, S Billan3, R Abdah-Bortnyak3, A Kuten3,4, U Tisch1,2 and H Haick1,2

1Department of Chemical Engineering, Technion – Israel Institute of Technology, Haifa 32000, Israel
2Russell Belrrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa 32000, Israel
3Oncology Division, Rambam Health Care Campus, Haifa 31096, Israel
4Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa 31096, Israel
Correspondence: Dr H Haick, E-mail: hhossam@technion.ac.il

5These three authors contributed equally to this work.

Received 15 April 2010; Revised 16 June 2010; Accepted 21 June 2010; Published online 20 July 2010.

Background: Tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of volatile organic compounds (VOCs). In this study, we investigated the ability of a nanosensor array to discriminate between breath VOCs that characterise healthy states and the most widespread cancer states in the developed world: lung, breast, colorectal, and prostate cancers.

Methods: Exhaled alveolar breath was collected from 177 volunteers aged 20–75 years (patients with lung, colon, breast, and prostate cancers and healthy controls). Breath from cancerous subjects was collected before any treatment. The healthy population was healthy according to subjective patient's data. The breath of volunteers was examined by a tailor-made array of cross-reactive nanosensors based on organically functionalised gold nanoparticles and gas chromatography linked to the mass spectrometry technique (GC-MS).

Results: The results showed that the nanosensor array could differentiate between ‘healthy’ and ‘cancerous’ breath, and, furthermore, between the breath of patients having different cancer types. Moreover, the nanosensor array could distinguish between the breath patterns of different cancers in the same statistical analysis, irrespective of age, gender, lifestyle, and other confounding factors. The GC-MS results showed that each cancer could have a unique pattern of VOCs, when compared with healthy states, but not when compared with other cancer types.

Conclusions: The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer.

Keywords: breath; volatile biomarker; nanosensor; GC-MS

Cancer kills more than seven million people every year. The most widespread cancers in the developed world, accounting for half of the cancer deaths, are prostate, lung, and colorectal cancers for men, and breast, colorectal, and lung cancers for women (Culter, 2008; Jemal et al, 2008). The prognosis of a cancer patient improves considerably if the disease is discovered at an early stage, when the tumour is still localised (Hirsch et al, 2001; Kalogerakos et al, 2008). However, early detection is possible only through widespread and screening, because of the asymptomatic onset of the disease. The currently available techniques do not always fulfill the requirements for reliable discrimination between cancer patients and healthy subjects. For instance, the impact of computed tomography screening on lung cancer mortality and the benefit of the prostate-specific antigen blood test for prostate cancer screening are uncertain (Culter, 2008). Screening methods such as colonoscopy for colorectal cancer and mammography for breast cancer are very reliable, but these methods are far from ideal. Colonoscopy is invasive and extremely unpleasant to the patient (Culter, 2008; Jemal et al, 2008). Mammography uses X-rays which may cause radiation-induced mutations. In addition, image quality depends on the breast structure, so that it is not applicable to certain segments of the screening population, such as young at-risk women (young women with a family history of breast cancer and/or BRCA mutations) (Bermejo-Perez et al, 2008) and women with dense breast tissue (~25% of women over the age of 40 years) (Mandana, 2003; Andrew and Srinivasan, 2008).

The analysis of volatile organic compounds (VOCs) that are linked to cancer is a new frontier in medical diagnostics because it is non-invasive and potentially inexpensive (Amann et al, 2007; Mazzone, 2008). The principle behind this approach is based on cell biology. In particular tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of VOCs (Singer and Nicolson, 1972; Kneepkens et al, 1994; Alberts et al, 2002). These VOCs can be detected either directly from the headspace of cancer cells (Bajaj et al, 2009; Barash et al, 2009; Filipiak et al, 2010) or through exhaled breath (see Amann et al, 2007; Ligor et al, 2008; Mazzone, 2008; Bajtarevic et al, 2009; Horvath et al, 2009; Ligor et al, 2009 and bibliography therein), as cancer-related changes in the blood chemistry lead to measurable changes in the breath by exchange through the lung (Horvath et al, 2009). In this study, we report that a tailor-made array of cross-reactive sensors based on organically functionalised gold nanoparticles (GNPs) discriminates between breath VOCs of healthy controls and of patients suffering from lung, breast, colorectal, and prostate cancers. Moreover, we report on the ability of these GNP sensors to distinguish between the breath patterns of different cancer types in the same pattern analysis, irrespective of age, gender, lifestyle, and other confounding factors. We find that these results compare favourably with breath testing via a chemical analysis of the constituent compounds by gas chromatography linked with mass spectroscopy (GC-MS). The results reported in this study could lead to the development of a cost-effective, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available techniques used for the diagnosis of cancer.

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British Journal of Cancer - Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors




ONCOLOGÍA
Actualidad Ultimas noticias - JANOes y agencias -
Una nueva técnica detecta la presencia de tumores a través del aliento
JANO.es y agencias · 12 Agosto 2010 10:33

Esta “nariz electrónica” ha sido desarrollada por científicos israelíes, que publican sus resultados en el “'British Journal of Cancer”



Una nueva técnica de análisis respiratorio desarrollada por científicos del Instituto Tecnológico Israelí podría ser capaz de diagnosticar cánceres de pulmón, mama, intestino y próstata utilizando un sensor diseñado para detectar variaciones químicas en el aliento.

El invento, cuyos resultados se publican en el British Journal of Cancer, necesita todavía unos años para desarrollar todo su potencial, aunque, de ser viable, supondría un método “económico, fácil de usar y portátil para mejorar la detección precoz del cáncer”, apuntan los autores.

Para demostrar su eficacia, los científicos analizaron el aliento de 177 personas, algunas sanas y otras con varios tipos de cáncer, para detectar distintas sustancias químicas emitidas desde la superficie de las células cancerosas a medida que crecen.

Los hallazgos se basan en investigaciones previas publicadas por científicos del mismo instituto el año pasado, donde se demostraba que un sensor fabricado con nanopartículas de oro podía detectar el cáncer de pulmón en el aliento.

“Si se confirman estos resultados iniciales en estudios a gran escala, esta nueva tecnología podría volverse una herramienta sencilla para el diagnóstico precoz del cáncer, junto con el diagnóstico por imagen”, comenta el director del estudio, Abraham Kuten.



British Journal of Cancer 2010;103:542–551
http://www.nature.com/bjc/journal/v103/n4/full/6605810a.html

British Journal of Cancer
http://www.nature.com/bjc/index.html


Israel Institute of Technology
http://www.cs.technion.ac.il/

Actualidad Ultimas noticias - JANOes y agencias - Una nueva tecnica detecta la presencia de tumores a traves del aliento - JANO.es - ELSEVIER