Gene expression profiling and cancer-related pathways in type I endometrial carcinoma.
BACKGROUND
Malignant transformation of type I endometrium involves alteration in gene expression with subsequent uncontrolled proliferation of altered cells.


OBJECTIVE
The main objective of the present study was to identify the cancer-related genes and gene pathways in the endometrium of healthy and cancer patients.


METHODS
Thirty endometrial tissues from healthy and type I EC patients were subjected to total RNA isolation. The RNA samples with good integrity number were hybridized to a new version of Affymetrix Human Genome GeneChip 1.0 ST array. We analyzed the results using the GeneSpring 9.0 GX and the Pathway Studio 6.1 software. For validation assay, quantitative real-time polymerase chain reaction was used to analyze 4 selected genes in normal and EC tissue.


RESULTS
Of the 28,869 genes profiled, we identified 621 differentially expressed genes (2-fold) in the normal tissue and the tumor. Among these genes, 146 were up-regulated and 476 were down-regulated in the tumor as compared with the normal tissue (P < 0.001). Up-regulated genes included the v-erb-a erythroblastic leukemia viral oncogene homolog 3 (ErbB3), ErbB4, E74-like factor 3 (ELF3), and chemokine ligand 17 (CXCL17). The down-regulated genes included signal transducer and activator transcription 5B (STAT5b), transforming growth factor A receptor III (TGFA3), caveolin 1 (CAV1), and protein kinase C alpha (PKCA). The gene set enrichment analysis showed 10 significant gene sets with related genes (P < 0.05). The quantitative polymerase chain reaction of 4 selected genes using similar RNA confirmed the microarray results (P < 0.05).


CONCLUSIONS
Identification of molecular pathways with their genes related to type I EC contribute to the understanding of pathophysiology of this cancer, probably leading to identifying potential biomarkers of the cancer.
Department of Physiology, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Fatma S A
FS
Saghir
Isa Mohamed
IM
Rose
Ahmad Zailani Hatta Mohd
AZ
Dali
Zainab
Z
Shamsuddin
A Rahman A
AR
Jamal
Norfilza Mohd
NM
Mokhtar
D000328:Adult; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis