Loss of ZG16 is associated with molecular and clinicopathological phenotypes of colorectal cancer

Autor: Liang Wang, Hui Meng, Wencai Li, Lisa A. Boardman
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Adenoma
Male
0301 basic medicine
Cancer Research
DNA Copy Number Variations
Survival
Colorectal cancer
Kaplan-Meier Estimate
MLH1
lcsh:RC254-282
Disease-Free Survival
03 medical and health sciences
0302 clinical medicine
Lectins
Biomarkers
Tumor
Genetics
medicine
Carcinoma
Humans
ZG16
Zymogen granule protein 16
business.industry
Copy number variation
Microsatellite instability
DNA Methylation
Prognosis
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
digestive system diseases
Gene Expression Regulation
Neoplastic
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
DNA methylation
Cancer research
Immunohistochemistry
Colitis
Ulcerative
CpG Islands
Female
Microsatellite Instability
Gene expression
Colorectal Neoplasms
business
Research Article
Zdroj: BMC Cancer, Vol 18, Iss 1, Pp 1-11 (2018)
BMC Cancer
ISSN: 1471-2407
DOI: 10.1186/s12885-018-4337-2
Popis: Background Zymogen granule protein 16 (ZG16) is one of the most significantly down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to further evaluate its expression changes and investigate its association with molecular and clinicopathological characteristics of CRC. Methods We applied quantitative RT-PCR to determine expression difference between tumor and matched normal tissues from 23 CRC patients. To further validate the down-regulation in tumor tissues, we performed immunohistochemistry (IHC) analysis in 40 paraffin-embedded normal-tumor pairs and 22 colon tissues with a variety of diseases. To evaluate if the ZG16 gene changes were associated with clinicopathological characteristics, we further analyzed the gene expression and copy number changes from The Cancer Genome Atlas (TCGA) and Oncomine datasets. Results Quantitative RT-PCR confirmed significant down-regulation (~ 130-fold) of ZG16 in all tumor tissues. ZG16 expression was in an organ-specific manner with an extremely high expression in normal epithelial cells of small intestine, colon and rectum. IHC analysis showed that ZG16 protein was completely lost in all of 40 CRC tissues, and partially lost in premalignant adenomatous polyps (adenomas) and chronic ulcerative colitis tissues. Gene expression and copy number changes were significantly associated with multiple molecular and clinicopathological features of CRC including microsatellite instability (MSI), MLH1 silencing, CpG island methylator phenotype, hyper-mutation status, gender, presence of synchronous adenomas, and histological type (P
Databáze: OpenAIRE
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