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Monday, November 19, 2012

Validated Gene Targets Associated with Curatively Treated Advanced Serous Ovarian Carcinoma



Validated Gene Targets Associated with Curatively Treated Advanced Serous Ovarian Carcinoma: Publication year: 2012
Source:Gynecologic Oncology

Objectives
High-grade serous ovarian cancer (HGSOC) mostly presents at an advanced stage and has a low overall survival rate. However, a subgroup of patients are seemingly cured after standard initial therapy. We hypothesize that molecular profiles of these patients vary from long-term survivors who recur.
Methods
Patients with advanced HGSOC who underwent primary cytoreductive surgery and platinum-based chemotherapy were identified from The Cancer Genome Atlas (TCGA) and institutional (MSKCC) samples. A curative-intent group was defined by recurrence-free survival of >5years. A long-term recurrent group was composed of patients who recurred but survived >5years.
RNA was hybridized to Affymetrix U133A transcription microarrays. The NanoString nCounter gene expression system was used for validation in an independent patient population.

Results
In 30 curative and 84 recurrent patients, class comparison identified twice as many differentially expressed probes between the groups than expected by chance alone. TCGA and MSKCC data sets had 19 overlapping genes. Pathway analyses identified over-represented networks that included nuclear factor kappa B (NFkB) transcription and extracellular signal-regulated kinase (ERK) signaling. External validation was performed in an independent population of 28 curative and 38 recurrent patients. Three genes (CYP4B1, CEPT1, CHMP4A) in common between our original datasets remained differentially expressed in the external validation data.

Conclusions
There are distinct transcriptional elements in HGSOC from patients likely to be cured by standard primary therapy. Three genes have withstood rigorous validation and are plausible targets for further study, which may provide insight into molecular features associated with long-term survival and chemotherapy resistance mechanisms.

Highlights

► Tumors from long-term, disease-free ovarian cancer survivors have a unique gene expression profile.
► Long-term, disease-free ovarian cancer survivors provide insight into the mechanisms of acquired drug resistance.

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