Predictive biomarkers of platinum and taxane resistance using the transcriptomic data of 1816 ovarian cancer patients

Fekete, János Tibor; Õsz, Ágnes; Pete, Imre; Nagy, Gyula Richárd; Vereczkey, Ildikó; Győrffy, Balázs

doi:10.1016/j.ygyno.2020.01.006

Cited by 59 publications

(56 citation statements)

References 35 publications

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“…Ovarian cancer is the second most common cause of death related to gynecologic malignancies, particularly high-grade serous ovarian cancer (HGSOC) [146]. The front-line treatment consists of cytoreductive surgical resection followed by combination treatment of platinum and taxane drugs.…”

Section: Taxane Resistance In Ovarian Cancermentioning

confidence: 99%

Mechanisms of Taxane Resistance

Maloney

Hoover

Morejon-Lasso

et al. 2020

Cancers

121

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The taxane family of chemotherapy drugs has been used to treat a variety of mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite the improved survival time and reduction of tumor size observed in some patients, many have no response to the drugs or develop resistance over time. Taxane resistance is multi-faceted and involves multiple pathways in proliferation, apoptosis, metabolism, and the transport of foreign substances. In this review, we dive deeper into hypothesized resistance mechanisms from research during the last decade, with a focus on the cancer types that use taxanes as first-line treatment but frequently develop resistance to them. Furthermore, we will discuss current clinical inhibitors and those yet to be approved that target key pathways or proteins and aim to reverse resistance in combination with taxanes or individually. Lastly, we will highlight taxane response biomarkers, specific genes with monitored expression and correlated with response to taxanes, mentioning those currently being used and those that should be adopted. The future directions of taxanes involve more personalized approaches to treatment by tailoring drug–inhibitor combinations or alternatives depending on levels of resistance biomarkers. We hope that this review will identify gaps in knowledge surrounding taxane resistance that future research or clinical trials can overcome.

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Section: Taxane Resistance In Ovarian Cancermentioning

confidence: 99%

Mechanisms of Taxane Resistance

Maloney

Hoover

Morejon-Lasso

et al. 2020

Cancers

121

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“…The prognostic significance of Plk1 (Affymetrix ID: 202240_at) and Ki-67 (Affymetrix ID: MKI-67 212023_s_at) mRNA expression was evaluated by the online Kaplan-Meier Plotter (www.kmplot.com) (40). This platform covers gene expression data and survival information of OC patients from Gene Expression Omnibus database.…”

Section: Kaplan-meier Plottermentioning

confidence: 99%

“…First, to study the clinical impact of Plk1 and Ki-67 mRNA expression in OC patients, we evaluated the correlation between these markers and patients' survival based on Kaplan Meier plotter analyses according to our previous investigations (40). Survival curves were plotted for stage I+II and stage III+IV tumors to discriminate early and advanced stage disease.…”

Section: Plk1 and Ki-67 Gene Expression And Survival Of Oc Patientsmentioning

confidence: 99%

The Prognostic Relevance of the Proliferation Markers Ki-67 and Plk1 in Early-Stage Ovarian Cancer Patients With Serous, Low-Grade Carcinoma Based on mRNA and Protein Expression

et al. 2020

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Since type and duration of an appropriate adjuvant chemotherapy in early-stage ovarian cancer (OC) are still being debated, novel markers for a better stratification of these patients are of utmost importance for the design of an improved chemotherapeutical strategy. In contrast to numerous cancer studies on cellular proliferation based on the immunohistochemistry-driven evaluation of protein expression, we compared mRNA and protein expression of two independent markers of cellular proliferation, Ki-67 and Plk1, in a large cohort of 243 early-stage OC and their relationship with clinicopathological features and survival. Based on marker expression we demonstrate that early-stage OC patients (stages I/II, low-grade, serous) with high expression (Ki-67, Plk1) had a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to patients with low expression (Ki-67, Plk1). Remarkably, based on mRNA expression this significant difference got lost in advanced stages (III/IV): At least for PFS, high levels of Ki-67 and Plk1 correlate with moderately better survival compared to patients with low expressing tumors. Our data suggest that in addition to Ki-67, Plk1 is a novel marker for the stratification of early-stage OC patients to maximize therapeutic efforts. Both, Ki-67 and Plk1, seem to be better suited in early-stages (I/II) as therapeutical targets compared to advanced-stages (III/IV) OC.

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“…p=service&cancer=ovar, accessed 20 February 2020. ) [17] . For protein analysis, we compare Clinical Proteomic Tumor Analysis Consortium (CPTAC) samples in UALCAN ( http://ualcan.path.uab.edu/ accessed 18 February 2020).…”

Section: Online Analysismentioning

confidence: 99%

Identification of WTAP-related genes by weighted gene co-expression network analysis in ovarian cancer

Wang

et al. 2020

Preprint

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Background : WTAP modulating other genes in the manner of transcriptional and post-transcriptional regulation, in particular, acting as a N6-methyladenosine writer or binding to the 3’-untranslated region of mRNA, promotes a variety of tumors. However, its roles and mechanisms in ovarian cancer are unknown. Results : In this study, using univariate Cox analysis and online CPTA analysis, we found that WTAP was a poor prognostic factor for ovarian cancer and its protein expression level was higher in ovarian cancer compared to normal tissue. Subsequently, we identified a module containing 133 genes that were carefully related to WTAP expression through weighted gene co-expression network analysis. By calculating hazard ratio of these genes and comparing their differences in the WTAP high-expression group and the low-expression group, we noticed there was a significantly positive correlation between WTAP and two poor survival-related genes: FAM76A and HBS1L. Conclusion : Our research suggests that the WTAP-HBS1L / FAM76A axis may play an essential role in ovarian cancer progression and provide new ideas for ovarian cancer research.

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Predictive biomarkers of platinum and taxane resistance using the transcriptomic data of 1816 ovarian cancer patients

Cited by 59 publications

References 35 publications

Mechanisms of Taxane Resistance

Mechanisms of Taxane Resistance

The Prognostic Relevance of the Proliferation Markers Ki-67 and Plk1 in Early-Stage Ovarian Cancer Patients With Serous, Low-Grade Carcinoma Based on mRNA and Protein Expression

Identification of WTAP-related genes by weighted gene co-expression network analysis in ovarian cancer

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