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

Haitham Amal, Lu Ding, Bin Bin Liu, Ulrike Tisch, Zhen Qin Xu, Da You Shi, Yan Zhao, Jie Chen, Rui Xia Sun, Hu Liu*, Sheng Long Ye, Zhao You Tang, Hossam Haick

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


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.

Original languageAmerican English
Pages (from-to)4135-4146
Number of pages12
JournalInternational Journal of Nanomedicine
StatePublished - 2012
Externally publishedYes


  • GC-MS
  • Hepatocarcinoma
  • Metastasis
  • Sensor
  • Volatile organic compound


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