Abstract
The efficacy of breath volatile organic compounds (VOCs) analysis for the screening of patients bearing breast cancer lesions has been demonstrated by using gas chromatography and artificial olfactory systems. On the other hand, in-vitro studies suggest that VOCs detection could also give important indications regarding molecular and tumorigenic characteristics of tumor cells. Aim of this study was to analyze VOCs in the headspace of breast cancer cell lines in order to ascertain the potentiality of VOCs signatures in giving information about these cells and set-up a new sensor system able to detect breast tumor-associated VOCs. We identified by Gas Chromatography-Mass Spectrometry analysis a VOCs signature that discriminates breast cancer cells for: i) transformed condition; ii) cell doubling time (CDT); iii) Estrogen and Progesterone Receptors (ER, PgR) expression, and HER2 overexpression. Moreover, the signals obtained from a temperature modulated metal oxide semiconductor gas sensor can be classified in order to recognize VOCs signatures associated with breast cancer cells, CDT and ER expression. Our results demonstrate that VOCs analysis could give clinically relevant information about proliferative and molecular features of breast cancer cells and pose the basis for the optimization of a low-cost diagnostic device to be used for tumors characterization.
Highlights
The efficacy of breath volatile organic compounds (VOCs) analysis for the screening of patients bearing breast cancer lesions has been demonstrated by using gas chromatography and artificial olfactory systems
Only few studies have been addressed to the analysis of the VOCs released in the headspace of breast cancer-derived cell lines to increase the comprehension of the metabolic alterations associated with breast cancer transformation and enable the development of cost-effective and non-invasive breast cancer diagnostic tools[24]
In this work we have analyzed the VOCs emitted by the culture media of different breast cancer cell lines with the Gas Chromatography–Mass Spectrometry (GC-MS) and a temperature modulated metal oxide gas sensor highlighting the potentialities of this approach to obtain diagnostic information with high impact in the clinical management of breast cancer patients
Summary
The efficacy of breath volatile organic compounds (VOCs) analysis for the screening of patients bearing breast cancer lesions has been demonstrated by using gas chromatography and artificial olfactory systems. Personalized cancer treatments require a complex invasive and time-consuming analysis of many different parameters, such as histological type and grading, evaluation of Estrogen Receptor (ER), Progesterone Receptor (PgR), HER2 and Ki67 protein expression by immunohistochemistry (IHC), gene mutation analysis by DNA sequencing and chromosomal alterations by Fluorescence In Situ Hybridization (FISH)[3] Taken together all these aspects stimulate the research of new diagnostic tools that could promptly support the clinicians in breast cancer treatment decision-making. Breath analysis could be applied in the early identification of tumors, but in order to provide histological and molecular information useful to clinicians for the selection of the specific treatment of a neoplastic lesion, VOCs analysis should be applied directly to tumor To this regard, in vitro experiments demonstrate that artificial olfactory systems can discriminate between tumor and normal cell lines and among tumors-derived cells bearing different molecular alterations[16,17,18,19,20,21]. Only few studies have been addressed to the analysis of the VOCs released in the headspace of breast cancer-derived cell lines to increase the comprehension of the metabolic alterations associated with breast cancer transformation and enable the development of cost-effective and non-invasive breast cancer diagnostic tools[24]
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