The scent fingerprint of hepatocarcinoma: in-vitro metastasis prediction with volatile organic compounds (VOCs)

Abstract

Background: Hepatocellular carcinoma (HCC) is a common and aggressive form of cancer. Due to a high rate of postoperative recurrence, the prognosis for HCC is poor. Subclinical metastasis is the major cause of tumor recurrence and patient mortality. Currently, there is no reliable prognostic method of invasion. Aim: To investigate the feasibility of fingerprints of volatile organic compounds (VOCs) for the in-vitro prediction of metastasis. Methods: Headspace gases were collected from 36 cell cultures (HCC with high and low metastatic potential and normal cells) and analyzed using nanomaterial-based sensors. Predictive models were built by employing discriminant factor analysis pattern recognition, and the classification success was determined using leave-one-out cross-validation. The chemical composition of each headspace sample was studied using gas chromatography coupled with mass spectrometry (GC-MS). Results: Excellent discrimination was achieved using the nanomaterial-based sensors between (i) all HCC and normal controls; (ii) low metastatic HCC and normal controls; (iii) high metastatic HCC and normal controls; and (iv) high and low HCC. Several HCC-related VOCs that could be associated with biochemical cellular processes were identified through GC-MS analysis. Conclusion:The presented results constitute a proof-of-concept for the in-vitro prediction of the metastatic potential of HCC from VOC fingerprints using nanotechnology. Further studies on a larger number of more diverse cell cultures are needed to evaluate the robustness of the VOC patterns. These findings could benefit the development of a fast and potentially inexpensive laboratory test for subclinical HCC metastasis.

A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions

“…The GC-MS chromatograms of pristine Tenax material from unused ORBO TM 420 Tenax TA sorption tubes showed several prominent peaks corresponding to five VOCs that are probably contaminants of the Tenax sorbent material of the collection tubes. The VOCs were tentatively identified by spectral library match (Compounds library of the National Institute of Standards and Technology, Gaithersburg, MD USA, see section S1.2 in the SOM) as methylene chloride, acetaldehyde, ℒ-cysteine sulphonic acid, malonic acid and naphthalene (Amal et al , 2012). These substances were disregarded in the subsequent comparative analysis.…”

Investigation of VOCs associated with different characteristics of breast cancer cells

“…Recent in vitro studies provided evidences for the existence of VOCs signatures characteristic of genetic mutations associated with lung cancer cells or with the metastatic potential of hepatocarcinoma cell lines 20 21 37 . As a consequence, we analyzed our data to evidence the influence of cancer cell indicators such as the CDT and the expression of the most important diagnostic and prognostic immunohistochemical markers used for the characterization of breast cancer biopsy, namely ER, PgR and HER2.…”

“…GC-MS data were analyzed using Welch’s t-test and MANOVA to evaluate the statistical difference between the patterns of VOCs related to the cancer cells 48 37 .…”

Current Challenges in Volatile Organic Compounds Analysis as Potential Biomarkers of Cancer

“…In this type of sampler sorbent traps serve as adsorption material, and extraction is based, as in SPME, on the equilibrium principles [ 124 ]. Offline sorbent trapping was also used by Amal et al (with the use of TD) [ 71 ]. Finally, cryoconcentration was also used prior to analysis in a study, in order to investigate VOCs produced by leukaemia cell line.…”