Elevation of Prostaglandin E 2 in Lung Cancer Patients with Digital Clubbing

Abstract

To test the hypothesis that digital clubbing in patients with lung cancer reflects elevated systemic levels of prostaglandin E2 (PGE2), we quantified levels of the major urinary PGE2 metabolite in 29 patients with lung cancer with or without clubbing. We found that digital clubbing was associated with markedly elevated urinary levels of PGE2 metabolite. These findings highlight a potential role for PGE2 in the pathogenesis of digital clubbing. Furthermore, this result identifies a lung cancer subpopulation that may uniquely benefit from cyclooxygenase inhibition.

Cyclooxygenase-2 Expression in Non-Small Cell Lung Cancer Correlates With Hypertrophic Osteoarthropathy

“…It was reported as a significant presenting symptom in 20% of patients with primary lung tumors [1]. Whereas the pathophysiological mechanisms underlying HO remain unknown, recent studies have suggested a role for COX2-derived PGE2 [2,3]. Prostaglandins are important mediators of the inflammatory response to a broad array of diverse pathologic processes.…”

“…(Ann Thorac Surg 2016;101:e51-3) Ó 2016 by The Society of Thoracic Surgeons H ypertrophic osteoarthrpathy (HO) is a paraneoplastic syndrome that can present as digital clubbing, periostosis of tubular bones, and synovial effusions [1]. This condition was shown to occur in 20% of nonsmall cell lung cancers (NSCLCs) and is generally associated with advanced stage disease (stage III and IV) [1][2][3]. HO has also been shown to occur with other cardiopul-monary diseases including chronic pulmonary infections, cystic fibrosis, and congenital or acquired cardiomyopathies involving right to left shunts [1][2][3].…”

“…This condition was shown to occur in 20% of nonsmall cell lung cancers (NSCLCs) and is generally associated with advanced stage disease (stage III and IV) [1][2][3]. HO has also been shown to occur with other cardiopul-monary diseases including chronic pulmonary infections, cystic fibrosis, and congenital or acquired cardiomyopathies involving right to left shunts [1][2][3]. The pathophysiology of HO remains unknown.…”

“…The pathophysiology of HO remains unknown. Various mechanisms have been suggested including the circulation of a soluble growth factor that evades pulmonary catabolism either because of excessive synthesis or because of right to left circulatory bypass [2,3]. A role for prostaglandin E2 (PGE2) has been documented in the context of lung cancer as urinary PGE2 levels correlated with HO and digital clubbing symptoms were improved by rofecoxib, a cyclooxygenase-2 (COX2) inhibitor [2,3].…”

Cyclooxygenase-2 inhibitors for non-small-cell lung cancer: A phase II trial and literature review

“…Kozak et al (29) found that markedly elevated urinary levels of the major PGE 2 metabolite, which is a downstream signaling molecule of COX-2, were observed in patients with digital clubbing. Patients with high urinary levels of PGE 2 may benefit from COX-2 inhibitors.…”