Tu1756 The Inflammatory Microenvironment in Duodeno-Esophageal Reflux Induced Esophageal Carcinogenesis in a Sequential Rat Model

Abstract

Introduction: Previous studies have established that surgical trauma is associated with significant transient alterations in cell-mediated immune function. Surgery-related immunosuppression may impact the patient's ability to deal with infection. Also, tumor growth has been shown in murine studies to be increased after surgical trauma. Cell-mediated immunosuppression after resection of a primary tumor may impair the host's ability to eradicate or contain residual tumors cells. This microarray study of perioperative T-lymphocyte (TLC) gene expression was undertaken in an effort to better understand the impact of colorectal resection (CR) on cell-mediated immune function. Method: Patients who underwent elective laparoscopic right hemicolectomy (RHC) for benign colonic disease (BCD) who had enrolled in an IRB approved blood/data bank for whom frozen preand postoperative TLC's were available were eligible for this study. Benign pathology patients were chosen in order to determine the impact of surgical trauma alone, independent of the potential effects of a cancer on immune function. Preoperative (PreOp) and postoperative day1 (POD1) blood samples were utilized. TLC's were isolated from the blood using a combination of gradient centrifugation and magnetic micro-bead separation. TLC's were subsequently lysed and total RNA extracted. cRNA was made from RNA hybridized to HG-U133APLUS oligonucleotide array. PreOp vs POD1 expression data was analyzed via Limma paired analysis to find differently expressed genes. (p.0.05 significant) and consistency of significance was analyzed via Empirical Bayes statistics (B>0 Sig.). Clinical data is presented as mean ± SD. Results: Nineteen patients (12 males/7 female, mean age 65.8± 12.8 years) met the entry criteria. The mean incision length was 7.8± 3.5cm and mean length of stay was 6.3±2.6 days. All TLC expression data met the affymetrix data QC standards. A total of 39 genes showed significant changes on POD1; 21were up-regulated and 18 were down regulated (B=0.055.3). The expression changes of 7 genes in this group were strongly significant (ABCG-1, TMEM49, FAM100B and PIM1 were upregulated and IFI44L, STAT1 and UCP2 were down regulated; P =0.02 and B =4.1-5.3). Enrichment analysis confirmed that these gene changes were likely to have significant effects on 7 signaling pathways and 3 functional categories i.e.; cell proliferation, hematological function and immune response. Conclusion: Surgical trauma affected gene expression of circulating TLC's in the immediate postoperative period. Altered gene expression may impact TLC growth and proliferation as well as immune function. These changes must be validated at the protein level and additional patients studied. Also, the duration of these changes, after surgery, must be determined. Finally, a similar study in cancer patients is also needed.