Yonsei Med J.  2016 Jul;57(4):872-878. 10.3349/ymj.2016.57.4.872.

Estimation of Prognostic Marker Genes by Public Microarray Data in Patients with Ovarian Serous Cystadenocarcinoma

• Yang SD
• Jang SS
• Han JA
• Park HS
• Kim JI

• KMID: 2374117
• DOI: http://doi.org/10.3349/ymj.2016.57.4.872

Abstract

PURPOSE
Lymphatic invasion (LI) is regarded as a predictor of the aggressiveness of ovarian cancer (OC). However, LI is not always the major determinant of long-term patient survival. To establish proper diagnosis and treatment for OC, we analyzed differentially expressed genes (DEGs) for patients with serous epithelial OC, with or without LI, who did or did not survive for 5 years.
MATERIALS AND METHODS
Gene expression data from 63 patients with OC and LI, and 35 patients with OC but without LI, were investigated using an Affymetrix Human Genome U133 Array and analyzed using The Cancer Genome Atlas (TCGA) database. Among these 98 patients, 16 survived for 5 years or more. DEGs were identified using the Bioconductor R package, and their functions were analyzed using the DAVID web tool.
RESULTS
We found 55 significant DEGs (p<0.01) from the patients with LI and 20 highly significant DEGs (p<0.001) from those without it. Pathway analysis showed that DEGs associated with carbohydrate metabolism or with renal cell carcinoma pathways were enriched in the patients with and without LI, respectively. Using the top five prognostic marker genes, we generated survival scores that could be used to predict the 5-year survival of patients with OC without LI.
CONCLUSION
The DEGs identified in this study could be used to elucidate the mechanism of tumor progression and to guide the prognosis and treatment of patients with serous OC but without LI.

Keyword

Gene expression; microarray analysis; ovarian cancer; prognosis

MeSH Terms

Cystadenocarcinoma, Serous/*genetics/*mortality/pathology
Databases, Genetic
Female
Gene Expression Regulation, Neoplastic
Humans
Microarray Analysis
Middle Aged
Ovarian Neoplasms/*genetics/*mortality/pathology
Prognosis
Regression Analysis
Retrospective Studies
Survival Rate

Figure

• 

  Fig. 1 Heat map of gene expression profiles from patients with OC. The rows represent genes, and columns represent individual patients. Red indicates a high, and green indicates a low expression level. Differentially expressed genes between 5-year survival and nonsurvival groups were selected from all patients with OC (p<0.01) (A), patients with lymphatic invasion (p<0.01) (B), and patients without lymphatic invasion (p<0.001) (C). OC, ovarian cancer.

• 

  Fig. 2 Clustering of 5-year survival and nonsurvival groups of patients with OC without lymphatic invasion. (A) Manhattan distance plot of gene expression profiles in 20 survival-related genes and their association with patients without lymphatic invasion. (B) Cluster dendrogram of gene expression profiles and their association with patients without lymphatic invasion. OC, ovarian cancer.

• 

  Fig. 3 Survival score values calculated by multiple linear regression analysis with the five prognostic marker genes. The Y-axis indicates the score values; the 5-year survival group showed positive values, while the nonsurvival group showed negative values.

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