Prediction of the Chemotherapeutic Efficacy for Advanced Pancreatic Cancer By Focused DNA Array Analysis Using Endoscopic Ultrasound-Guided Fine-Needle Aspiration

Abstract

Background: Patients with unresectable pancreatic cancers have extremely poor prognosis. The ineffective anti-cancer drugs, which cause adverse effect alone, should not be given to the patient with this dismal disease. It is an urgent investigational subject to predict the effectiveness of anti-cancer agent against pancreatic cancer prior to treatment. We examined the usefulness of Focused DNA Array (FDA) analysis using the pancreatic cancer tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) for the prediction of chemotherapeutic effect. Methods: Tissues from 21 unresectable pancreatic cancers were obtained by EUS-FNA using the 19 or 22-gauge needle. Total mRNA was harvested from each sample, and cDNA was composed by reverse transcription polymerase chain reaction (RT-PCR). Expression of RNA was evaluated using FDA which was restricted to 133 genes including drug-resistance related genes. The amount of RNA was expressed as the relative value to house keeping gene. Result: Gemcitabine (GEM) was given to 17 patients. One course of GEM regimen composed 1000 mg/m2 weekly administration for three weeks following one week rest. Eleven patients completed 3 courses or more of this regimen were divided into the following two groups. Three patients with PR and three patients with tumor marker reduction by 50% or more were classified as responders. The other five patients were classified as non-responders. By the FDA, we measured the mRNA expression of dCMP deaminase (DCD) and RRM1 genes, which may act as GEM-resistant factors, and deoxycytidine kinase (DCK) gene, which may act as GEM-sensitive factor. Our gene scoring was defined as following. When the mRNA amount was half or less in GEM-resistant factors or twice or more in GEM-sensitive factor, compared to the mean amount of corresponding mRNA in all 21 tissues, one point was added to the gene score. When the mRNA amount was twice or more in GEM-resistant factors or half or less in GEM-sensitive factor, one point was subtracted from the gene score. In six responders, four tumors showed +1 (gene score) and two did +2. In five non-responders, one tumor indicated −1, three did zero point, and one did +1. When the gene score of +1 or more point was defined as a predictive indicator for GEM-efficacy, the sensitivity, specificity and accuracy were 100%, 80% and 91%, respectively. Conclusion: The FDA chip is loaded with many other genes related to 5-fluorouracil, cisplatin, molecular targeting agents, and so on, besides GEM. The gene analysis using a sample taken by EUS-FNA might be useful to predict the chemothrapeutic efficacy for patients with unresectable pancreatic cancer.