Student Project done by:
PENG Boya (54877602)
The slides can be downloaded here
Background
- Ovarian cancer is a gynecological malignancy with the highest mortality rate.
- Patients lack specific symptoms in the early stage, patients present with Stage III or IV at initial diagnoses.
- Patients are often given cytoreductive surgery supplemented with platinum- and paclitaxel-based chemotherapy as standard frontline treatment.
- Prolonged treatment with chemotherapy often gives rise to multidrug resistance mechanisms including increase in detoxification, suppression of apoptotic signaling and stimulation of proliferation.
Chemotherapy resistance is the main obstacle affecting the prognosis of patients with ovarian cancer.
Microarray Data Preprocessing
Download Gene expression microarray dataset: GSE15709.CEL
- 5 platinum-resistant ovarian cancer cell A2780
- 5 platinum-sensitive ovarian cancer cell A2780
In Biocondutor R 3.3.3:
Normalization : MAS5calls, RMA, Check A/P detection rates
Quality Control- Array checking
Quality Control- Hierarchical clustering & PCA
Differential gene expression
The differential expression and significance were calculated by a linear model using limma package and empirical Bayes method. 4,304 significantly differentially expressed genes, of which 2,920 upregulated genes and 1,384 downregulated genes were found (p<0.05).
Functional analysis
Significant enriched GO terms (Top 30)
KEGG pathway by HTSanalyzeR
ClusterProfiler
Signaling pathways generated by KEGG enrichment analysis of differentially expressed genes.
p53 signaling pathways and relevant functions, including cell senescence, cell cycle, apoptosis, DNA repair, angiogenesis and metastasis.
Hypothesis & Proposal
IGF-BP3 and relevant IGF/Ras/MAPK or IGF/PI3K/AKT pathway induce chemoresistance in ovarian cancer cells ?
