Abstract
High-grade serous epithelial ovarian cancer (HGSOC) is the fifth leading cause of cancer death in women and the first among gynecological malignancies. Despite an initial response to standard chemotherapy, most HGSOC patients relapse. To improve treatment options, we must continue investigating tumor biology. Tumor characteristics (e.g., risk factors and epidemiology) are valuable clues to accomplish this task. The two most frequent risk factors for HGSOC are the lifetime number of ovulations, which is associated with increased oxidative stress in the pelvic area caused by ovulation fluid, and a positive family history due to genetic factors. In the attempt to identify novel genetic factors (i.e., genes) associated with HGSOC, we observed that several genes in linkage with HGSOC are expressed in the ciliated cells of the fallopian tube. This finding made us hypothesize that ciliated cells, despite not being the cell of origin for HGSOC, may take part in HGSOC tumor initiation. Specifically, malfunction of the ciliary beat impairs the laminar fluid flow above the fallopian tube epithelia, thus likely reducing the clearance of oxidative stress caused by follicular fluid. Herein, we review the up-to-date findings dealing with HGSOC predisposition with the hypothesis that fallopian ciliated cells take part in HGSOC onset. Finally, we review the up-to-date literature concerning genes that are located in genomic loci associated with epithelial ovarian cancer (EOC) predisposition that are expressed by the fallopian ciliated cells.
Highlights
Ovarian cancers include three main types—epithelial ovarian cancers (EOC), sex-cord stromal tumors, and germ cell tumors—with EOC being the most frequent and lethal among them
C20orf85 and Sperm-Associated Antigen 6 (SPAG6) were the only genes within their own genomic interval to be differentially expressed between FTE and High-grade serous epithelial ovarian cancer (HGSOC) samples (Supplementary Table S3), and Serine/Threonine Kinase 33 (STK33) was the closest gene to SNP rs16937956 comparing high‐grade serous epithelial ovarian cancers (HGSOC) and micro‐dissected fallopian tube epithelia. b According to the Human Protein Atlas (HPA) antibody tissue validation
In an attempt to identify novel candidate genes associated with EOC, we discovered that several of these genes are expressed in the ciliated cells of the FTE, and are responsible for regulating cilia motility
Summary
Ovarian cancers include three main types—epithelial ovarian cancers (EOC), sex-cord stromal tumors, and germ cell tumors—with EOC being the most frequent and lethal among them. EOC has an estimated age-standardized rate (ASR) of six new cases per year per 100,000 persons [1], which, according to European Commission guidelines, makes EOC a rare tumor [2]. To improve EOC patients’ clinical outcome, we must diagnose EOC at earlier stages, and stratify patients according to best treatment options and to identify novel therapeutic targets. For all these reasons, it is crucial to continue investigating EOC tumor biology and clinical characteristics (e.g., risk factors, clinic, and epidemiology), which contain valuable information to accomplish this task [4]
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