Imaging mass spectrometry provides fingerprints for distinguishing hepatocellular carcinoma from cirrhosis.

MALDI imaging mass spectrometry (MALDI IMS) is a powerful tool for comprehending the spectrum of peptides/proteins expressed in tissue sections. The aim of the present study was to investigate, using MALDI IMS, the proteome of hepatocellular carcinomas (HCC) and to compare it with peritumoral cirrhosis so as to characterize new biomarkers of HCC. Frozen liver tissues corresponding to HCC and background cirrhosis (n = 30) were selected and subjected to MALDI IMS. We found a set of proteins/peptides with a differential intensity level that most accurately delineated cancer from adjacent cirrhotic tissue. Using a support vector machine algorithm, we generated a classification model in the train set that enabled segmenting images from the independent validation set and that in most cases matched histologic analysis. The most discriminating peak (m/z 8565) more intense in HCC was characterized as the monomeric ubiquitin. An immunohistochemical study in a large series of HCC/cirrhosis sampled on tissue microarray supported that ubiquitin was overexpressed in HCC. We demonstrated also that this increase was not related to an upregulation of ubiquitin gene transcription in HCC, thus suggesting a post-transcriptional mechanism. This approach might provide a new tool for diagnosis of difficult HCC cases and an opportunity for identifying candidate biomarkers.