Abstract
Precise diagnosis at the molecular level is essential for the improvement of surgery and treatment. High-throughput and spatial-resolved mass spectrometric (MS) methods for in situ detection of metabolites on tissue samples can reveal the dysregulation of metabolism in abnormal tissue and help identification of tumor. We here report a nondestructive MS method named as tip-contact sampling/ionization (TCSI)-MS technology which can quickly acquire lipidomic information from liver tissue and thereby realize tumor identification. Using this technology, fatty acids and lipids at the liver tissue surface can be rapidly imprinted onto a silicon nanowire tip attached with reduced graphene oxide (rGO) and sensitively detected by on-chip MS. With proper data pretreatment and statistical analysis, the clinical primary hepatocellular carcinoma (HCC) tissues can be discriminated from the nontumor parts. In addition, we found that a panel of adjacent dual peaks' ratio can be used to build a prediction model in artificial neural networks (ANN), resulting in high accuracy (91.7-98.3%) for tumor discrimination. Ratiometric TCSI-MS imaging using a selected dual peaks' ratio can greatly enhance the spatial resolution of tumor margin. The feature ratiometric data of lipid molecules may guide the study of metabolism pathways involved in hepatocarcinoma and ultimately become new metabolic biomarkers in clinical diagnosis. The present work demonstrated that the TCSI-MS technology may pave a novel way for surgery guidance and precision diagnosis in tissue biopsy.
Highlights
H epatocellular carcinoma (HCC) is the major type of primary liver cancer,[1] which has become the second most common cause of cancer related mortality worldwide after lung cancer.[2]
Other solid phase microextraction (SPME) probes followed with MS analysis or touch spray mass spectrometry (TS-MS) have provided alternative offline strategies for metabolites detection at the surface of cancerous tissues.[14,15]
Our previous work indicated that vertical silicon nanowire (SiNWs) array is an ideal substrate for surface assisted laser desorption/ionization mass spectrometry (SALDI-MS) and can be acted upon as a sampling chip when contacted with tissues.[16]
Summary
Each probe can only be applied for one-point sampling and is not appropriate for high-throughput detection or localization of tumor information. Individual variation did exist, the specific pattern of feature ratio values showed a distinctive panel in tumors compared with paratumors if the normal liver tissue of each patient was regarded as the background (Figure 3) These results further indicate that TCSI-MS coupled with ratiometric-methodology show its great potential in the off-line cancer diagnosis. The finding of the dysregulation of these “dual peaks” may imply an abnormal linoleic acid and arachidonic acid pathway involved in the liver malignancy, which could be used as the potential diagnostic biomarker and the therapy target in the future Dysregulation of these ratio values is effective indicator of tumor margin when ratiometric TCSI-MS imaging was conducted on the HCC tumor tissue (Figure 4).
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