+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer

Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer

Bmc Cancer 13: 549

Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with standard platinum-based chemotherapy. Twelve patient tumours demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumours from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using an Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumours from the resistant group and the sensitive group. Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NF κB/ERK gene signalling networks. This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. In addition, our results provide a pathway context for further experimental validations, and the findings are a significant step towards future therapeutic interventions.

(PDF emailed within 0-6 h: $19.90)

Accession: 053671731

Download citation: RISBibTeXText

PMID: 24237932

DOI: 10.1186/1471-2407-13-549

Related references

High-resolution mapping of genomic imbalance and identification of gene expression profiles associated with differential chemotherapy response in serous epithelial ovarian cancer. Neoplasia 7(6): 603-613, 2005

γ-Glutamyl cyclotransferase contributes to tumor progression in high grade serous ovarian cancer by regulating epithelial-mesenchymal transition via activating PI3K/AKT/mTOR pathway. Gynecologic Oncology 149(1): 163-172, 2018

Identification of high-grade serous ovarian cancer miRNA species associated with survival and drug response in patients receiving neoadjuvant chemotherapy: a retrospective longitudinal analysis using matched tumor biopsies. Annals of Oncology 27(4): 625-634, 2016

STAT1-associated intratumoural T H 1 immunity predicts chemotherapy resistance in high-grade serous ovarian cancer. Journal of Pathology. Clinical Research 2(4): 259-270, 2016

Chemotherapy is of Value in Second Line and Beyond, Relapsed High-grade, Serous Epithelial Ovarian Cancer: An Analysis of Outcomes Obtained With Oral Etoposide. American Journal of Clinical Oncology 41(4): 379-384, 2016

Identification of Prognostic Groups in High-Grade Serous Ovarian Cancer Treated with Platinum-Taxane Chemotherapy. Cancer Research 75(15): 2987-2998, 2015

Cancer stem cells, epithelial-mesenchymal transition, and drug resistance in high-grade ovarian serous carcinoma. Human Pathology 44(11): 2373-2384, 2014

Serum HE4 and CA125 as predictors of response and outcome during neoadjuvant chemotherapy of advanced high-grade serous ovarian cancer. Tumour Biology 35(12): 12389-12395, 2015

Measuring response to neoadjuvant chemotherapy in high-grade serous tubo-ovarian carcinoma: an analysis of the correlation between CT imaging and chemotherapy response score. International Journal of Gynecological Cancer 2019, 2019

Endocrine treatment of high grade serous ovarian carcinoma; quantification of efficacy and identification of response predictors. Gynecologic Oncology 152(2): 278-285, 2018

Epigenetic Regulation of the Homeobox Gene MSX1 Associates with Platinum-Resistant Disease in High-Grade Serous Epithelial Ovarian Cancer. Clinical Cancer Research 22(12): 3097-3104, 2018

Histopathologic response to neoadjuvant chemotherapy as a prognostic biomarker in tubo-ovarian high-grade serous carcinoma: updated Chemotherapy Response Score (CRS) results. International Journal of Gynecological Cancer 2019, 2019

Chemotherapy Response Score: Development and Validation of a System to Quantify Histopathologic Response to Neoadjuvant Chemotherapy in Tubo-Ovarian High-Grade Serous Carcinoma. Journal of Clinical Oncology 33(22): 2457-2463, 2015

Cumulative defects in DNA repair pathways drive the PARP inhibitor response in high-grade serous epithelial ovarian cancer cell lines. Oncotarget 8(25): 40152-40168, 2016

Outcomes of Women With High-Grade and Low-Grade Advanced-Stage Serous Epithelial Ovarian Cancer. Obstetrics and Gynecology 129(3): 439-447, 2017