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Gene Expression Profiling and Cancer-Related Pathways in Type I Endometrial Carcinoma
  1. Fatma S.A. Saghir, MMSc (Physiol)*,
  2. Isa Mohamed Rose, MMSc (Pathol),
  3. Ahmad Zailani Hatta Mohd Dali, MMSc (Obstet&Gynecol),
  4. Zainab Shamsuddin, MRCOG§,
  5. A Rahman A. Jamal, PhD and
  6. Norfilza Mohd Mokhtar, PhD*,
  1. * Departments of Physiology,
  2. Pathology, and
  3. Obstetrics and Gynecology, Universiti Kebangsaan Malaysia;
  4. § Department of Obstetrics and Gynecology, Hospital Kuala Lumpur, Kuala Lumpur; and
  5. UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia.
  1. Address correspondence and reprint requests to Norfilza Mohd Mokhtar, PhD, Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. E-mail: norfilza{at}


Introduction: 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.

Materials and 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 β receptor III (TGFβ3), 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.

  • Type I endometrial carcinoma
  • Microarray
  • Gene expression
  • Genomics
  • Pathway analysis

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