1515P - LncRNA H19, HOTAIR and MALAT1 as prognostic molecular biomarkers in GIST.

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics GIST
Sarcoma
Translational Research
Presenter Nadia Barraco
Citation Annals of Oncology (2017) 28 (suppl_5): v521-v538. 10.1093/annonc/mdx387
Authors N. Barraco1, L. Incorvaia1, G. Badalamenti1, F. Passiglia1, A. Listì1, R. Maragliano1, E. Musso1, E. Bronte1, D. Cabibi2, V. Calò1, M. Castiglia1, D. Fanale1, A. Galvano1, V. Gristina1, S. Ingrao2, L. Insalaco1, D. Massihnia1, A. Perez1, V. Bazan3, A. Russo1
  • 1Department Of Surgical, Oncological And Oral Sciences, Section Of Medical Oncology, University Of Palermo, Palermo, Italy, AOU Policlinico "Paolo Giaccone", 90127 - Palermo/IT
  • 2Department Of "scienze Per La Promozione Della Salute E Materno Infantile "g.d'alessandro", University Of Palermo, Palermo, Italy, AOU Policlinico "Paolo Giaccone", 90127 - Palermo/IT
  • 3Department Of "biomedicina Sperimentale E Neuroscienze Cliniche (bionec)", University Of Palermo, Palermo, Italy, AOU Policlinico "Paolo Giaccone", 90127 - Palermo/IT

Abstract

Background

Long non-coding RNAs (lncRNAs) are emerging as essential regulators of genetic and epigenetic networks. Their deregulation may underlie carcinogenesis suggesting their potential involvement in tumorigenic and metastatic processes, as well as their role as prognostic/predictive biomarkers for clinical use in patients with several solid tumors. Few studies evaluated lncRNAs expression in rare tumors such as Gastrointestinal Stromal Tumors (GISTs). Indeed, the upregulation of HOTAIR has been associated with tumor aggressiveness and metastasis, and poor survival of GIST patients. In order to gain more detailed insight on the molecular role of lncRNAs, we analyzed the expression levels of lncRNAs H19, MALAT1 and HOTAIR in tissue specimens of surgically resected GIST patients to evaluate the potential role of lncRNAs as prognostic biomarkers.

Methods

The expression of the lncRNAs H19, MALAT1 and HOTAIR was evaluated in a total of 40 pairs of disease formalin-fixed paraffin-embedded tissue and adjacent normal tissue from 40 GIST patients with localized and locally advanced disease using quantitative real-time reverse transcriptase.

Results

H19 was overexpressed in 50% GIST patients (p-value: 0.0496). MALAT1 was overexpressed in 45% GIST patients (p-value: 0.032). None of them had the related date with HOTAIR. Furthermore, the up-regulation of H19 has been found in 74% patients harboring cKIT mutations compared to 57% wild type patients (p-value: 0.042). Conversely the up-regulation of MALAT1 has been found in 76% patients harboring cKIT mutations compared to 100% wild type patients (p-value: 0.027). Finally, the up- regulation of H19 has been found in 100% patients with TTP < 3 months compared to 25% patients with TTP >3 months, while the up-regulation of MALAT1 has been found in 25% patients with TTP < 3 months compared to 75% patients with TTP >3 months.

Conclusions

H19 and MALAT1 appear upregulated in GIST patients according to the KIT- mutation status. These data would suggest a potential opposite prognostic value of both H19 and MALAT1 lncRNAs in these patients. The results of HOTAIR expression levels were indeterminated in all analyzed tumor samples, probably because HOTAIR has been degraded during its isolation. Further analyses are needed to confirm these data.

Clinical trial identification

Not applicable

Legal entity responsible for the study

University of Palermo

Funding

None

Disclosure

All authors have declared no conflicts of interest.