Abstract 4591: Differential expression of tight junction polarity genes in human colon cancer

Abstract

Abstract Tight junctions perform significant and multifactorial functions in cellular polarity maintenance and paracellular transport. A number of studies have found structural disruption of epithelial colon cells can significantly impact early tumorigenesis and progression. However, little is known about the direct contribution of polarity gene expression in human colon cancer development. We compared the expression of tight junction genes in colon cancer with normal control mucosa. Total RNA was extracted from fresh frozen tissue biopsies of six white male patients (N = 3 for early stage tumore, N = 3 for late stage tumor, and N = 2 for normal adjacent controls) and four unrelated normal colon mucosa from polyp-free individuals. We used the Qiagen RT2 Profiler PCR array to determine the expression of 84 genes in the tight junction pathway. Student's t test was used to compare the expression levels between different groups (control vs. early-stage tumor and late-stage tumor) using normalized gene expression data. Functional annotation clustering of statistically significant genes by group was conducted using DAVID. Significant (P<0.05) down regulation of claudin (CLDN5, CLDN6, CLDN7) expression was seen in both early and late-stage tumor compared with controls, all with fold change (FC)> 2; while CLDN1 (FC = 15) was only significantly upregulated (P = 0.0007) in early-stage tumor. Down regulation (FC>2) of polarity complex gene PARD6A (P<.001) and associated genes (JAM2, P<.001 and JAM3, P <.001) were present in both early and late-stage tumors along with associated down-regulation of tumor suppressor PTEN (P<.0001). We found differential expression of tight junction genes in normal versus colon tumor. Down regulation of polarity genes is likely to affect apico-basal polarity and promote random non-coordinated migration which can lead to disruption of epithelial structure and to carcinogenic tissue infiltration. Further larger studies are warranted to investigate the role of tight junction proteins in the progression of human colon tumor. Citation Format: Kathryn E. Royse, Liang Chen, Jocelyn Uriostegui, Michael Ittmann, David Y. Graham, Hashem El-Serag, Li Jiao. Differential expression of tight junction polarity genes in human colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4591. doi:10.1158/1538-7445.AM2015-4591