# Intertwined Relationship of WWOX and RUNX2 Proteins as a Biomarker for Predicting Response and Survival in Patients With Childhood Bone Cancer in North India: A Pilot Study

**Authors:** Priyanka Sharma, Shah Waliullah, Bhavesh Kumar, Ravindra Mohan, Devarshi Rastogi, Dharmendra Kumar, Wahid Ali

PMC · DOI: 10.7759/cureus.93160 · 2025-09-24

## TL;DR

This pilot study explores the role of WWOX and RUNX2 proteins in predicting outcomes for children with bone cancer in North India.

## Contribution

The study identifies RUNX2 overexpression as a potential biomarker for Ewing sarcoma progression and prognosis.

## Key findings

- RUNX2 expression was significantly higher in Ewing sarcoma tissues compared to controls.
- Most patients presented with advanced-stage disease and high metastasis rates at diagnosis.
- High mortality and reduced survival times were observed, highlighting poor prognosis.

## Abstract

Background: Ewing sarcoma (ES) is an aggressive bone cancer that predominantly affects children and adolescents. Despite advancements in treatment, the prognosis for patients with metastatic disease remains poor. This pilot study investigated the expression of WWOX and RUNX2 proteins in ES tissues from patients from North India and their potential as prognostic biomarkers.

Methods: Immunohistochemical analysis was performed on tumor samples from seven ES patients and five age-matched controls.

Results: The results revealed that RUNX2 expression was significantly elevated in ES tissues compared to controls (p = 0.005), while WWOX expression showed no significant difference (p = 0.876). Clinically, 71.4% of patients presented with stage IV disease, and 85.7% had metastasis at diagnosis. The Kaplan-Meier analysis demonstrated poor survival outcomes, with a high mortality rate (85.7%) and reduced median survival time.

Conclusion: These findings suggest that RUNX2 overexpression is a defining characteristic of ES and may contribute to tumor progression and metastasis. In contrast, WWOX does not appear to play a critical role in ES pathogenesis. The advanced stage at presentation and poor survival outcomes underscore the need for earlier detection and biomarker-driven interventions. Further research is warranted to validate RUNX2 as a prognostic biomarker and potential therapeutic target in ES.

## Linked entities

- **Genes:** WWOX (WW domain containing oxidoreductase) [NCBI Gene 51741], RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860]
- **Proteins:** WWOX (WW domain containing oxidoreductase), RUNX2 (RUNX family transcription factor 2)
- **Diseases:** Ewing sarcoma (MONDO:0012817), bone cancer (MONDO:0002129)

## Full-text entities

- **Genes:** RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, WWOX (WW domain containing oxidoreductase) [NCBI Gene 51741] {aka D16S432E, DEE28, EIEE28, FOR, FRA16D, HHCMA56}
- **Diseases:** ES (MESH:D012512), metastasis (MESH:D009362), Bone Cancer (MESH:D001859), tumor (MESH:D009369), stage IV disease (MESH:D007676)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12552799/full.md

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Source: https://tomesphere.com/paper/PMC12552799