Gene Expression Differences in Normal Esophageal Mucosa Associated with Regression and Progression of Mild and Moderate Squamous Dysplasia in a High-Risk Chinese Population

Abstract

A randomized, double-blinded, placebo-controlled 2 Â 2 factorial chemoprevention trial was conducted in Linxian, China to assess the effects of selenomethionine and celecoxib on the natural history of esophageal squamous dysplasia. Results from this study indicated that asymptomatic adults with mild dysplasia were more likely to show an improvement when treated with selenomethionine compared with placebo (P = 0.02). Prompted by this finding, we examined the molecular profiles associated with regression and progression of dysplastic lesions in normal mucosa from 29 individuals, a subset of the Linxian cohort, using the Affymetrix U133A chip. Twenty differentially expressed genes were associated with regression and 129 were associated with progression when we compared the change in gene expression over time. Genes associated with immune response (n = 15), cell cycle (n = 15), metabolism (n = 15), calcium transport or calcium ion activity (n = 10

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

“…15 In a recent study, SerpinA1 was among 129 genes whose elevated expression was associated with progression of esophageal squamous dysplasia. 32 Elevated levels of AAT have been detected in the serum of patients with SCC of the oral cavity. 33 Furthermore, expression of SerpinA3 has been documented in lung adenocarcinoma 34 and in tandem with SerpinA1 in human leukocyte antigen-positive cervical carcinoma.…”

Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions

“…As previous oral cavity microarray studies have focused on obtaining ''signature'' gene expression profiles of normal, premalignant and malignant oral tissues in the absence of treatment, direct comparisons with our study are not feasible (34,35,39). In a recent esophageal chemoprevention trial, Joshi and colleagues evaluated pretreatment and posttreatment gene expression profiles in histologically normal esophageal tissues in 29 patients with premalignant esophageal lesions and identified (40). Ten of these genes, which were associated with inflammation and immune suppression, showed up-regulation during lesional progression, whereas the expression of five genes associated with immune stimulation increased with regression (40).…”

“…Huang and colleagues showed that a FBR methanol extract reduced activator protein 1 (AP-1) activation by targeting mitogen-associated protein kinase pathways including ERKs, JNKs, and p38K, and also suppressed NFnB activation by inhibiting InBa phosphorylation (21). Notably, three potentially protumorigenic genes, i.e., COX-2, iNOS, and VEGF, all have NFnB-binding sites (40). Furthermore, AP-1 activation is associated with up-regulation of COX-2 and VEGF (41).…”

Gene expression profile of esophageal cancer in North East India by cDNA microarray analysis

“…Enhanced cell mig ration and tumor metastasis are associated with fluctuations in the activity of membrane transporters and ion channels that require K + channel activity [23] . Genes involved in calcium regulation and calcium signaling also seemed to be important in the progression of esophageal squamous dysplasia [24] . The deleted in colorectal cancer (DCC) gene, which was found to be upregulated in our study, is a candidate tumor suppressor gene which may be associated with differentiation and proliferation of normal cells.…”