Page 112 - ebook HCC

PROGRAMME AND ABSTRACTSAND ABSTRACTS
110
110 PROGRAMME GENEVA, SWITZERLAND EASL HCC SUMMIT 111
FEBRUARY 13 - 16, 2014

Poster Board Number B12

NEW INSIGHTS IN HOXA13 AND HOTTIP ROLE AS NOTES
PROGNOSTIC FACTORS IN HEPATOCELLULAR
CARCINOMA

1
2
Luca Quagliata , Matthias Matter ,Salvatore Piscuoglio , Tujana Boldanova ,
1
1
Luigi Tornillo , Markus Heim , Clemente Cillo , Luigi Terracciano 1
1
3
2
2
1 Institute of Pathology - University Hospital Basel, Switzerland, Department of
Biomedicine, Hepatology Laboratory, University Hospital Basel, Basel, Switzerland,
3 Federico II University Medical School, Naples, Italy
Corresponding author’s e-mail: luca.quagliata@usb.ch
Introduction: Previously, using gene expression data, we observed that among the
transcriptional factors family of HOX genes, HOXA13 is highly deregulated in hepatocellular
carcinoma samples (HCC). HOTTIP is a recently described lncRNA (long non-coding RNA)
located at the 5’ end of the HOXA locus (in physical contiguity with HOXA13) that binds the
WDR5/MLL complexes driving gene transcription along the entire HOXA locus. Lately, we
demonstrated for the first time that HOTTIP expression directly correlates with HOXA13
levels in HCC. Moreover, we reported that HOTTIP/HOXA13 deregulation as a key feature
in HCC development, controlling liver cancer cells apoptosis. Finally, we outlined HOTTIP/
HOXA13 expression levels as predictive markers of HCC patients’ outcome and disease BASIC SPEAKERS ABSTRACTS
BASIC POSTER ABSTRACTS Aims: Based on the analysis of Chromatin-Immunoprecipitation (ChiP) data, here we
progression.
further corroborate our findings by analysing a large cohort of HCC samples evaluating
HOXA13 levels and selected metastasis-associated genes directly regulated by HOXA13.
Methodology: A liver specific TMA (tissue microarray) has been immunohistochemically
stained using HOXA13, CK-7, CK-19, E-Cad (CDH1), Galectin-3, Prune and Nm23-H2
human-specific Abs. This TMA comprises a total of n=305 specimens, n=82 from normal
liver tissue, n=108 collected from cirrhotic patients and n=115 from HCCs. Staining have
been scored by expert pathologists and protein levels have been correlated with patients’
clinical-pathological data, including patients’ survival.
Results: HOXA13 is altered in 41% of analysed samples, further confirming our previous
reports. In addition, again corroborating our gene expression-based data, HOXA13
immunohistochemistry (IHC) analysis revealed that higher HOXA13 levels are associated
with poorer patients’ outcome and higher grading (both Edmondson and BCLC).
Increased HOXA13 expression is linked with high liver stem progenitor markers levels,
CK-7 and CK19. Furthermore, our data revealed that high HOXA13 expression is coupled
with diminished levels of E-Cad and increased Gal-3, Prune and Nm23-H2, providing a
molecular basis for its clinical association with metastasis formation in HCC.
Conclusions: Here we show that HOXA13 IHC-based protein levels can reliably predict
HCC disease outcome, thus further confirming our previous gene expression data
and making HOXA13 a suitable marker for liver carcinogenesis evaluation. Additional
experiments aiming to elucidate HOXA13 role in promoting metastasis are urgently
needed.