Early placenta insuline-like peptide (pro-EPIL): A novel biomarker in advanced and metastatic non-small cell lung cancer (NSCLC) patients treated by chemotherapy

Abstract

20069 Background: Some studies suggest a causal relationship between the early placenta insuline-like peptide encoded by the insulin-like 4 gene and cancer invasiveness. Methods: Serum concentrations of pro-EPIL were measured by ELISA using a novel two-site “sandwitch” assay, based on two monoclonal antibodies (mAb) raised against synthetic peptides analogous to two distinct regions of the pro-Epil polypeptide: mAb EPIL15, and biotinylated mAb EPIL02, used as the labelled indicator. The first mAb EPIL15 was purified and bound to a solid phase. Pro-EPIL was allowed to bind, and unbound proteins were removed by washing. The sensitivity limit of the assay was 3 ng/mL of synthetic peptide, and detection was linear over a range of at 3 pg to 200 ng of the synthetic peptide. As primary endpoint, we studied the Pro-EPIL distribution according to some clinico-biological prognostic factors. Results: Between July 2001 and April 2005, nineteen chemonaive NSCLC pts were treated by chemotherapy in our center and serum determinations of pro-EPIL were performed. Ten pts (63%) overexpressed pro-EPIL before start of chemotherapy with a median value of 1.06 ng/mL (range 0.01–6.75). Median age was 60 years (range 38–80), more than 90% of pts were men with an advanced or metastatic disease. Forty-two percent of pts had a large cell carcinoma subtype, with 25% of adenocarcinoma and 25% of epidermoid type. Immunologic evaluations were performed with a median value of the CD3+ lymphocites of 1290/mm3 (range 610–2138). Significant correlations were observed between age, serum alcaline phosphatase and CD3+ number. A border-line positive correlation was observed between pro-EPIL and CD3+ levels (P = 0.09, R2 = 0.5). Median OS for entire cohort was 7.5 months (95% CI, 5.5–9.4), with 67% deaths. Because our sample size was very low, no survival analysis were performed according to the baseline pro-EPIL value and other prognostic factors. A bootstrapping procedure is planned on our data. Conclusions: This results showed that pro-EPIL was overexpressed in the majority of advanced NSCLC pts. Interactions between this biomarker and immune system are possible. Furthemore, pro-EPIL as a therapeutic target might be tested in prospective studies. No significant financial relationships to disclose.