Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumour that shows early metastasis and resistance to chemotherapy. Current biomarkers focus on prognosis and diagnosis but there is a need to find novel biomarkers, which could, for example, identify patients at risk of cerebral metastases.
Pro-opiomelanocortin (POMC), the precursor of ACTH is a well-recognised biomarker of the ectopic ACTH syndrome1, of which SCLC is the most prevalent tumour type. The aim of this study is to determine if POMC has biomarker potential in patients with SCLC but without hormone driven clinical indications.
Initially, POMC was measured in the circulation of nude mice injected with the SCLC cell line, DMS 79 and left until the tumour reached four times the relative tumour volume (~800 mm3). POMC concentrations were elevated in all mice with a mean of 2150 pmol/l (n=5) and were significantly higher than a non-SCLC carcinoma xenograft (P<0.05). Interestingly the corticosterone levels were also elevated at 180 ng/ml compared to 85.4 ng/ml in non-engrafted animals.
In plasma samples from patients with SCLC, POMC levels ranged from <15 to >1500 pmol/l (n=25). Over 35% of patients had POMC levels in excess of the normal range. There was also strong correlation with current biomarkers, including caspase-cleaved cytokeratin 18 (P<0.0003), circulating tumour cells (P<0.005) and lactate dehydrogenase (P<0.001). POMC also showed a weak correlation with alkaline phosphatase, full-length cytokeratin 18 and nucleosomal DNA.
We have shown that POMC is an effective biomarker in the circulation of mice with a SCLC xenograft and is highly elevated in a large subset of patients with SCLC. This suggests that POMC maybe a useful biomarker for SCLC and should be investigated to see if it identifies metastatic potential and chemoresistance.
Reference: 1. Oliver R, Davis JR & White A. Pituitary 2003 6 119126.