RUNX2 and WWOX genes as molecular biomarkers and candidates for targeted therapy in Egyptian patients with primary conventional osteosarcoma

Abeer A. BahnassyEmail author,
Eman Abdelzaher,
Rania Gaber,
Gamal Elhosseiny,
Awad Abdel Moniem A. Rafalla,
Abdel-rahman N. Zekri,
Ahmad El-Bastawisi,
Hend F. Yousif and
Layla Kamal Younis

Applied Cancer Research201636:4

DOI: 10.1186/s41241-016-0001-9

Received: 25 February 2016

Accepted: 25 October 2016

Published: 8 December 2016

Abstract

Background

The conventional osteosarcoma (OS) is the commonest primary malignant, bone tumor with complex genomic profiles and poor survival. Runt-related transcription factor 2 (RUNX2) and WW domain containing oxidoreductase (WWOX) genes are implicated in normal osteogenesis as well as in the development of primary conventional OS.

Methods

We retrospectively assessed protein and RNA expression of the RUNX2 and WWOX genes by quantitative real time PCR (qPCR) and immunohistochemistry (IHC) in 80 cases of primary OS and 20 normal control (NC) subjects. Proteins and RNA expression levels of both genes were correlated to clinico-pathological features of the patients, progression free and overall survival (PFS& OS) rates.

Results

In OS, RUNX2 protein was detected in 72/80 (90%) cases compared to 4/20 (20%) NC samples (p. < 0.001) and RUNX2-RNA was up regulated (up to 103.2 folds) in 60/80 (75%) (p = 0.01). WWOX protein and RNA (up to 7.2 folds) were detected in all NC samples but in 24/80 (30%) and 20/80 (20%) OS cases; respectively (p. < 0.001 for each). The concordance between the RNA and protein expressions for RUNX2 and WWOX was significantly high (X_trend^2 = 6.33; p = 0.012 and X_trend^2 = 19, p < 0.001; respectively). A significant inverse relation existed between RUNX2 and WWOX RNA and protein (p = 0.032, p = 0.008). There was significant correlation between RUNX2 RNA/protein, high tumor grade and stage (p = <0.001; each); RUNX2 RNA and male gender, tumor site and metastasis (p = 0.007, 0.041, 0.003; respectively). WWOX protein associated significantly with advanced stage and metastasis (p = 0.001& 0.024; respectively) and WWOX RNA associated with metastasis (p = 0.003).

Conclusions

RUNX2 and WWOX play opposing roles in the development and progression of OS. They could be used as sensitive prognostic biomarkers for OS patients and RUNX2 represents a promising candidate for targeted therapy.