期刊
BRITISH JOURNAL OF CANCER
卷 112, 期 7, 页码 1215-1222出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2015.81
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资金
- Ontario Institute for Cancer Research
- Ottawa Health Research Institute
- Banque de tissus et donnees of the Reseau de recherche sur le cancer of the Fond de recherche du Quebec Sante (FRQS)
- FRQS
- Government of Ontario
- Senate Advisory Research Committee
- Queen's University
- Cancer Research Society
Background: Chemotherapy resistance is a major determinant of poor overall survival rates in high-grade serous ovarian cancer (HGSC). We have previously shown that gene expression alterations affecting the NF-kappa B pathway characterise chemotherapy resistance in HGSC, suggesting that the regulation of an immune response may be associated with this phenotype. Methods: Given that intrinsic drug resistance pre-exists and is governed by both tumour and host factors, the current study was performed to examine the cross-talk between tumour inflammatory microenvironment and cancer cells, and their roles in mediating differential chemotherapy response in HGSC patients. Expression profiling of a panel of 184 inflammation-related genes was performed in 15 chemoresistant and 19 chemosensitive HGSC tumours using the NanoString nCounter platform. Results: A total of 11 significantly differentially expressed genes were found to distinguish the two groups. As STAT1 was the most significantly differentially expressed gene (P = 0.003), we validated the expression of STAT1 protein by immunohistochemistry using an independent cohort of 183 (52 resistant and 131 sensitive) HGSC cases on a primary tumour tissue microarray. Relative expression levels were subjected to Kaplan-Meier survival analysis and Cox proportional hazard regression models. Conclusions: This study confirms that higher STAT1 expression is significantly associated with increased progression-free survival and that this protein together with other mediators of tumour-host microenvironment can be applied as a novel response predictive biomarker in HGSC. Furthermore, an overall underactive immune microenvironment suggests that the pre-existing state of the tumour immune microenvironment could determine response to chemotherapy in HGSC.
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