High PARP1 Activity, Low PDXK Expression May Signal Poor Prognosis

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Patients with non-small cell lung cancer with high intratumoral PARP1 activity and low PDXK expression have poorer prognosis.
Patients with non-small cell lung cancer with high intratumoral PARP1 activity and low PDXK expression have poorer prognosis.

Patients with non-small cell lung cancer (NSCLC) with high intratumoral PARP1 activity and low PDXK expression have poorer prognosis compared to those with low PARP1 activity and high PDXK expression, according to a recent study published online ahead of print in Annals of Oncology.1

Judith Michels, MD, of the Cordeliers Research Centre in Paris, France, and fellow researchers examined two independent cohorts of patients with resected NSCLC in order to determine PARP1 and the level of its product, poly (ADP-ribose), through immunohistochemistry.

“Cisplatin-resistant NSCLC cells are often characterized by alterations in vitamin B-related metabolic processes, including the overexpression and hyperactivation of poly (ADP-ribose) PARP1 and the down-regulation of PDXK,” the researchers noted.

Using univariate and multivariate analyses, they found that intratumoral levels above median of PAR, but not PARP1 levels, had a negative prognostic impact in both the training and validation cohorts, which included 92 stage 1 subjects as well as 133 stage 1 and 2 subjects, respectively.

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Simultaneous assessment of PAR and PDXK protein levels improved risk stratification.

“These results underscore the clinical potential and possible therapeutic relevance of these biomarkers,” the authors concluded.

Reference

  1. Michels J, Adam J, Goubar A, et al. Negative prognostic value of high levels of intracellular poly (ADP-ribose) in non-small cell lung cancer. [published online ahead of print September 19, 2015]. Annals of Oncology. doi: 10.1093/annonc/mdv393.

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