Gene Expression Levels of the Prolyl Hydroxylase Domain Proteins and but Not Are Decreased in Primary Tumours and Correlate with Poor Prognosis of Patients with Surgically Resected Non-Small-Cell Lung Cancer.

BACKGROUND

Hypoxia correlates with poor prognosis in several cancer types, including lung cancer. Prolyl hydroxylase domain proteins (PHDs) play a role in cell oxygen sensing, negatively regulating the hypoxia-inducible factor (HIF) pathway. Our study aim was to evaluate , and mRNA expression levels in primary tumours and normal lungs of non-small-cell lung cancer (NSCLC) patients and to correlate it with selected regulators of HIF signalling, with clinicopathological characteristics and overall survival (OS).

METHODS

Tumour tissue samples were obtained from 60 patients with surgically resected NSCLC who were treated with radical surgery. In 22 out of 60 cases, matching morphologically normal lung tissue was obtained. , and mRNA expressions were measured using RT-qPCR.

RESULTS

The and mRNA levels in primary tumours were significantly decreased compared to those in normal lungs (both < 0.0001). and expression in tumours was positively correlated ( = 0.82; < 0.0001) and correlated well with HIF pathway downstream genes , and . Decreased and were associated with larger tumour size, higher tumour stage ( only) and squamous cell carcinoma. Patients with low and patients with low expression had shorter OS than patients with high ( = 0.02) and expression ( = 0.01). showed borderline independent prognostic values in multivariate analysis ( = 0.06). In contrast, we found no associations between expression and any of the observed parameters.

CONCLUSIONS

Our results show that reduced expression of and is associated with the development and progression of NSCLC. could be further assessed as a prognostic marker in NSCLC.