Biomarkers in ovarian cancer: To be or not to be

Arend, Rebecca C.; Martínez, Alba; Szul, Tomasz; Birrer, Michael J.

doi:10.1002/cncr.32595

Cited by 40 publications

(37 citation statements)

References 31 publications

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“…Ovarian cancer (OC), the third common gynecologic malignancy, contributes to the most cancer-caused mortality in women and increases with approximately 22,000 new cases and 14,180 deaths every year in the United States [1,2]. In histological subtypes, approximately 90% of OC is epithelial ovarian cancer, which consists of serous, endometrioid, and clear-cell ovarian carcinoma [2][3][4]. In the examination, the early-stage OC, such as the International Federation of Gynecology and Obstetrics (FIGO) stage-I/II, is difficult to diagnose because most symptoms of OC are nonspecific.…”

Section: Introductionmentioning

confidence: 99%

“…Due to the lack of early detection or screening test, about 70% of patients with OC are diagnosed at an advanced stage (FIGO stage III/IV), a mere 30% of which are expected to survive 5 years [1,6,7]. In contrast, the 5-year overall survival of patients with early-stage OC was reported to be 70-95% [3,4]. Therefore, it is definitely beneficial to reducing OC-caused mortality to develop more effective diagnostic methods for this disease.…”

Section: Introductionmentioning

confidence: 99%

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Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR‐23b‐3p/MRC2 Axis

Yang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ovarian cancer (OC), the third common gynecologic malignancy, contributes to the most cancer-caused mortality in women. However, 70% of patients with OC are diagnosed at an advanced stage, of which the 5-year survival is less than 30%. Long noncoding RNAs (long ncRNAs or lncRNA), a type of RNA with exceeding 200 nucleotides in length but no protein-coding capability, have been demonstrated to involve the pathogenesis of various cancers and show considerable potential in the diagnosis of OC. In this study, we found that the LINC00909 expression in tumor and serum specimens of OC patients was elevated, determined by real-time quantitative, and droplet digital PCR. In receiver operating characteristic (ROC) analysis, our results revealed that serum LINC00909 distinguished cancers from normal ovarian tissue with 87.8% of sensitivity and 69.6% of specificity (AUC, 81.2%) and distinguished serous ovarian cancer from normal ovarian tissue with 90.0% of sensitivity and 75.9% of specificity (AUC, 84.5%). Furthermore, we observed that the tumor and serum LINC00909 level was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and the Eastern Cooperative Oncology Group (ECOG) score (reflecting patients’ performance status). Also, patients with low serum LINC00909 level showed a longer overall (hazard ratio, HR = 1.874 , p = 0.0004 ) and progression-free ( HR = 1.656 , p = 0.0017 ) survival. Functional assays indicated that the elevation of LINC00909 expression contributes to cell proliferation, migration, and invasion capability of ovarian cancer cells. Besides, we demonstrated that LINC00909 functions as a competing endogenous RNA (ceRNA) of MRC2 mRNA by sponging miR-23-3p, and thereby promotes epithelial-to-mesenchymal transition (EMT) of ovarian cancer cells. Therefore, we highlight that the LINC00909/miR-23b-3p/MRC2 axis is implicated in the pathogenesis of ovarian cancer, and serum LINC00909 may be a promising biomarker for the diagnosis of OC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR‐23b‐3p/MRC2 Axis

Yang

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Most EOC patients (70%) are diagnosed in an advanced stage, i.e., International Federation of Gynecology and Obstetrics (FIGO) stage IIb -IV. The prognosis of advanced stage EOC is poor, with a 5-year survival rate of 20-30% [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

“…There is a need of more tools and assays to predict the clinical response to chemotherapy in EOC patients [3]. Ideally, this would avoid suboptimal treatment and prevent delay of optimal treatment, and thus clinical deterioration, unnecessary side effects of inadequate chemotherapeutics, and high societal costs.…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy sensitivity testing on ovarian cancer cells isolated from malignant ascites

Ouden¹,

Zaman

Dylus

et al. 2020

Oncotarget

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Background: In epithelial ovarian cancer (EOC), 15-20% of the tumors do not respond to first-line chemotherapy (paclitaxel with platinum-based therapy), and in recurrences this number increases. Our aim is to determine the feasibility of cell proliferation assays of tumor cells isolated from malignant ascites to predict in vitro chemotherapy sensitivity, and to correlate these results with clinical outcome.Materials and Methods: Ascites was collected from twenty women with advanced EOC. Cell samples were enriched for tumor cells and EOC origin was confirmed by intracellular staining of CK7, surface staining of CA125 and EpCAM, and HE4 gene expression. In vitro sensitivity to chemotherapy was determined in cell proliferation assays using intracellular ATP content as an indirect measure of cell number. In vitro drug response was quantified by calculation of the drug concentration at which cell growth was inhibited with 50%. Clinical outcome was determined using posttreatment CA125 level.Results: Cell samples of twenty patients were collected, of which three samples that failed to proliferate were excluded in the analysis (15%). Three other samples were excluded, because clinical outcome could not be determined correctly. In twelve of the fourteen remaining cases (86%) in vitro drug sensitivity and clinical outcome corresponded, while in two samples (14%) there was no correspondence.Conclusions: Our study demonstrates the feasibility of drug sensitivity tests using tumor cells isolated from ascites of advanced EOC patients. Larger observational studies are required to confirm the correlation between the in vitro sensitivity and clinical outcome.

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“…Unfortunately, most patients are diagnosed with a late stage disease and the five-year survival for these patients has remained static at around 30% [2]. The standard of care for the majority of HGSOC patients is primary cytoreductive (debulking) surgery, followed by adjuvant platinum and paclitaxel chemotherapy [3]. Progress in the treatment of ovarian cancer has seen the introduction of targeted therapies, such as bevacizumab and ploy(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and a plethora of immunotherapy trials [4].…”

Section: Introductionmentioning

confidence: 99%

HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells

Ali

Zhang

Maguire

et al. 2020

Cancers

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Histone deacetylase 6 (HDAC6) is a unique histone deacetylating enzyme that resides in the cell cytoplasm and is linked to the modulation of several key cancer related responses, including cell proliferation and migration. The promising anti-cancer response of the first-generation HDAC6 catalytic inhibitors continues to be assessed in clinical trials, although its role in high grade serous ovarian cancer is unclear. This study investigated HDAC6 tumor expression by immunohistochemistry in high-grade serous ovarian cancer (HGSOC) tissue samples and a meta-analysis of HDAC6 gene expression in ovarian cancer from publicly available data. The pharmacological activity of HDAC6 inhibition was assessed in a patient-derived model of HGSOC. HDAC6 was found to be highly expressed in HGSOC tissue samples and in the patient-derived HGSOC cell lines where higher HDAC6 protein and gene expression was associated with a decreased risk of death (hazard ratio (HR) 0.38, (95% confidence interval (CI), 0.16–0.88; p = 0.02); HR = 0.88 (95% CI, 0.78–0.99; p = 0.04)). Similarly, the multivariate analysis of HDAC6 protein expression, adjusting for stage, grade, and cytoreduction/cytoreductive surgery was associated with a decreased risk of death (HR = 0.19 (95% CI, 0.06–0.55); p = 0.002). Knock-down of HDAC6 gene expression with siRNA and protein expression with a HDAC6 targeting protein degrader decreased HGSOC cell proliferation, migration, and viability. Conversely, the selective inhibition of HDAC6 with the catalytic domain inhibitor, Ricolinostat (ACY-1215), inhibited HDAC6 deacetylation of α-tubulin, resulting in a sustained accumulation of acetylated α-tubulin up to 24 h in HGSOC cells, did not produce a robust inhibition of HDAC6 protein function. Inhibition of HGSOC cell proliferation by ACY-1215 was only achieved with significantly higher and non-selective doses of ACY-1215. In summary, we demonstrated, for the first time, that HDAC6 over-expression in HGSOC and all ovarian cancers is a favorable prognostic marker. We provide evidence to suggest that inhibition of HDAC6 catalytic activity with first generation HDAC6 inhibitors has limited efficacy as a monotherapy in HGSOC.

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Biomarkers in ovarian cancer: To be or not to be

Cited by 40 publications

References 31 publications

Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR‐23b‐3p/MRC2 Axis

Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR‐23b‐3p/MRC2 Axis

Chemotherapy sensitivity testing on ovarian cancer cells isolated from malignant ascites

HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells

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