High-grade serous ovarian cancer (HGSOC) constitutes the majority of all ovarian cancer cases and has staggering rates of both refractory and recurrent disease. While most patients respond to the initial treatment with paclitaxel and platinum-based drugs, up to 25% do not, and of the remaining that do, 75% experience disease recurrence within the subsequent two years. Intrinsic resistance in refractory cases is driven by environmental stressors like tumor hypoxia which alter the tumor microenvironment to promote cancer progression and resistance to anticancer drugs. Recurrent disease describes the acquisition of chemoresistance whereby cancer cells survive the initial exposure to chemotherapy and develop adaptations to enhance their chances of surviving subsequent treatments. Of the environmental stressors cancer cells endure, exposure to hypoxia has been identified as a potent trigger and priming agent for the development of chemoresistance. Both in the presence of the stress of hypoxia or the therapeutic stress of chemotherapy, cancer cells manage to cope and develop adaptations which prime populations to survive in future stress. One adaptation is the modification in the secretome. Chemoresistance is associated with translational reprogramming for increased protein synthesis, ribosome biogenesis, and vesicle trafficking. This leads to increased production of soluble proteins and extracellular vesicles (EVs) involved in autocrine and paracrine signaling processes. Numerous studies have demonstrated that these factors are largely altered between the secretomes of chemosensitive and chemoresistant patients. Such factors include cytokines, growth factors, EVs, and EV-encapsulated microRNAs (miRNAs), which serve to induce invasive molecular, biophysical, and chemoresistant phenotypes in neighboring normal and cancer cells. This review examines the modifications in the secretome of distinct chemoresistant ovarian cancer cell populations and specific secreted factors, which may serve as candidate biomarkers for aggressive and chemoresistant cancers.
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Construction of integrated microRNA and mRNA immune cell signatures to predict survival of patients with breast and ovarian cancer
In the tumor microenvironment, immune cells have emerged as key regulators of cancer progression. While much work has focused on characterizing tumor‐related immune cells through gene expression profiling, microRNAs (miRNAs) have also been reported to regulate immune cells in the tumor microenvironment. Using regression‐based computational methods, we have constructed for the first time, immune cell signatures based on miRNA expression from The Cancer Genome Atlas breast and ovarian cancer datasets. Combined with existing mRNA immune cell signatures, the integrated mRNA‐miRNA leukocyte signatures are better able to delineate prognostic immune cell subsets within both cancers compared to the mRNA or miRNA signatures alone. Moreover, using the miRNA signatures, the anti‐inflammatory M2 macrophages emerged as the most significantly prognostic cell type in the breast cancer data (HR [hazard ratio]: 12.9; CI [confidence interval]: 3.09‐52.9;
- NSF-PAR ID:
- 10462461
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Genes, Chromosomes and Cancer
- Volume:
- 58
- Issue:
- 1
- ISSN:
- 1045-2257
- Page Range / eLocation ID:
- p. 34-42
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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