Gene expression signature as a surrogate marker of microvascular invasion on routine hepatocellular carcinoma biopsies.

BACKGROUND & AIMS: Microvascular invasion (MVI), a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma (HCC), is only detectable by microscopic examination of the surgical specimen. We aimed to define a transcriptomic signature associated with MVI in HCC than can be applied to formalin-fixed paraffin-embedded (FFPE) biopsies for use in clinical practice. METHODS: To identify a gene expression signature related to MVI by using NanoString technology, we selected a set of 200 genes according to the literature and RNA-sequencing data obtained from a cohort of 150 frozen HCC samples previously published. We used 178 FFPE-archived HCC samples, including 109 surgical samples for the training set and 69 paired pre-operative biopsies for the validation set. In 14 cases of the training set, a paired biopsy was available and was also analyzed. RESULTS: We identified a 6-gene signature (ROS1, UGT2B7, FAS, ANGPTL7, GMNN, MKI67) strongly associated with MVI in the training set of FFPE surgical HCC samples, with 82% accuracy (sensitivity 82%, specificity 81%, AUC 0.82). The NanoString gene expression was highly correlated in 14 paired surgical/biopsy HCC samples (mean R: 0.97). In the validation set of 69 FFPE HCC biopsies, the 6-gene NanoString signature predicted MVI with 74% accuracy (sensitivity 73%, specificity 76%, AUC 0.74). Moreover, on multivariate analysis, the MVI signature was associated with overall survival in both sets (hazard ratio 2.29; 95% CI 1.03-5.07; p = 0.041). CONCLUSION: We defined a 6-gene signature that can accurately predict MVI in FFPE HCC biopsy samples, which is also associated with overall survival, although its survival impact must be confirmed by extensive study with further clinical data. LAY SUMMARY: Microvascular invasion, a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma, is only detectable by microscopic examination of a surgical specimen. In this study, we defined a relevant surrogate signature of microvascular invasion in hepatocellular carcinoma that may be applied in clinical practice with routine tumor biopsy and integrated into the therapeutic strategy.

A New Tactic for Label-Free Recognition of ß-Trophin via Electrochemiluminescent Signalling on an AuNPs Supported Immuno-Interface.

In this paper, a new strategy is reported for preparing a label-free ß-trophin electrochemiluminescent (ECL) immunosensor with good specificity, reproducibility and stability. An aquagel polymer from the hydrolysis of (3-aminopropyl) trimethoxysilane acted as the linker to catch the Au nanoparticles (AuNPs) on the indium-tin oxide (ITO) substrate by a two-step method. The AuNPs play an important role in enhancing ECL and immobilizing the ß-trophin antibody. This immunosensor can test for ß-trophin using luminol as an ECL probe. The ECL intensity at the resultant sensor, after the direct immuno-interaction, was proportional to the concentration of ß-trophin and had a low limit of quantification as 4.2 ng mL-1. After deep discussions on the ECL mechanism of this immunosensor, we found that its sensitivity is greatly affected by the presence of oxygen and improved under deoxygenation. We believe that this sensor can be used for clinical cases.