Dataset Information

Altered JS-2 expression in colorectal cancers and its clinical pathological relevance.

ABSTRACT: JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer.

SUBMITTER: Lam AK

PROVIDER: S-EPMC5528300 | biostudies-other | 2011 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Wiskott-Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis. We used microarrays for the validation of a WIPF1 co-expression module which was developed on two publically available datasets. Keywords: disease state analysis For the generation of our own microarray data set, 62 CRC patients undergoing elective standard oncological resection at the Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité, were prospectively recruited.

Project description:Ubiquitin-conjugating enzyme E2T (UBE2T) plays a significant role in carcinogenesis. Previous studies have demonstrated that UBE2T promotes the development and progression of numerous types of cancer. However, the association between UBE2T expression and colorectal cancer (CRC) remains unclear. In the present study, UBE2T protein expression was examined in the tissues of patients with CRC via immunohistochemistry. In addition, UBE2T expression data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA). In the clinical samples, the associations between UBE2T expression and clinicopathological factors were evaluated by the ?2 or Fisher's exact tests. In TCGA data, associations between UBE2T expression and clinical characteristics were evaluated using a logistic regression model. Overall survival was analyzed using Kaplan-Meier and Cox regression analyses. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting assays were used to examine UBE2T expression in normal and CRC cell lines. Gene set enrichment analysis (GSEA) was performed on the dataset from TCGA. UBE2T protein was highly expressed in the cytoplasm of tumor cells in 29/50 clinical samples, whereas in the adjacent normal tissues, it was only highly expressed in 2/50 samples. Furthermore, UBE2T expression was associated with the N classification (P<0.001), clinical TNM stage (P<0.001) and histological grade of tumors (P=0.010). Survival analysis showed an association between high UBE2T expression and poor survival rate in patients with CRC (P=0.002). Cox regression analysis also revealed that UBE2T expression was an independent prognostic factor for these patients (P=0.006). RT-qPCR and western blotting showed that UBE2T was expressed in CRC cell lines at higher levels than that in a normal colon cell line. Analysis of TCGA data revealed that UBE2T was highly expressed in tumor samples compared with normal samples, but was not associated with prognosis. GSEA showed that high expression of UBE2T was associated with the Kyoto Encyclopedia of Genes and Genomes pathways ‘cell cycle’, ‘oxidative phosphorylation’, ‘DNA replication’, ‘p53 signaling pathway’, ‘ubiquitin mediated proteolysis’ and ‘pentose phosphate pathway’. These results indicate that UBE2T may play an important role in the progression of CRC and serve as a potential prognostic factor during the treatment of cancer.

Dataset Information

Altered JS-2 expression in colorectal cancers and its clinical pathological relevance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets