scholarly journals The prognostic role of aberrant copy number of DDB1, PRPF19, CDKN1B, and с-Myc genes in ovarian cancer patients

2020 ◽  
Vol 49 ◽  
Author(s):  
E. V. Verenikina ◽  
N. A. Petrusenko ◽  
M. M. Kecheryukova
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Copy Number ◽  
Genetic Locus ◽  
Adverse Outcomes ◽  
Research Centre ◽  
Genetic Loci ◽  
Relative Copy Number ◽  
Frequent Relapses

Rationale: Ovarian cancer is the leading death cause in gynecological malignancies. More than 70% of the patients are diagnosed with progressing disease extending to outside the true pelvis. The 5-year survival of ovarian cancer patients remains low (about 47%) due to frequent relapses and drug resistance. Identification of markers for early diagnosis and relapse prediction could improve the outcomes of the disease.Aim: To assess relative copy number of cancer-associated genetic loci c-Myc, CDK12, CDKN1B, PRPF19, ERBB2, DDB1, GAB2, COL6A3 in the tumor cells of ovarian cancer, in order to identify potential prognostic oncomarkers in ovarian cancer patients.Materials and methods: The study included 50 women aged 27 to 70 years with ovarian cancer T1-3сN0-1M0-1, Gr.  2 (stages  I–IV), who received their elective treatment in the National Medical Research Centre for Oncology in 2015 to 2019. The study was based on samples of genomic DNA from paraffinized blocks of tumor and “healthy” tissues. Relative copy numbers of 8 genetic loci (c-Myc, CDK12, CDKN1B, PRPF19, ERBB2, DDB1, GAB2, COL6A3) was assessed by RT-qPCR technique. Relative copy quantitation of a genetic locus was calculated as 2-ΔCt. The dose of the locus studied was considered equal to diploid set (2n) if RCQtumor/healthy was about 1. If RCQtumor/healthy was>1.5 or<0.5, then the locus dose was considered increased (≥ 3n) or decreased (≤ 1n), respectively.Results: For all genetic loci, an increase of relative copy quantitation in the ovarian tumor cells was observed compared to that in “healthy” tissues. There was a  significant (р<0.05) aberrant copy quantitation of 4  genes: c-Myc (р=0.001), DDB1 (р=0.002), PRPF19 (р=0.0001), and CDKN1B (р=0.001). We identified differential thresholds for these genes that made it possible to predict an unfavorable disease course in the patients (р<0.05). The strongest association with the risk of adverse outcomes was found for increased copy number of PRPF19 (odds ratio (OR) 7.3; р=0.0001) and c-Myc (OR 6.8; р=0.001). Conclusion: In this study, we determined the prognostic value of 4 oncogenic drivers, namely, DDB1, PRPF19, CDKN1B, and с-Myc, whose increased copy number was associated with an adverse disease prognosis in ovarian cancer patients.

scholarly journals Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 130
Author(s):  
Michal Kielbik ◽  
Izabela Szulc-Kielbik ◽  
Magdalena Klink
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cytotoxic T Cells ◽  
Adaptive Immune Response ◽  
Ovarian Cancer Cells ◽  
Immunogenic Cell Death ◽  
Antigen Presenting ◽  
Molecular Patterns

Immunogenic cell death (ICD) is a type of death, which has the hallmarks of necroptosis and apoptosis, and is best characterized in malignant diseases. Chemotherapeutics, radiotherapy and photodynamic therapy induce intracellular stress response pathways in tumor cells, leading to a secretion of various factors belonging to a family of damage-associated molecular patterns molecules, capable of inducing the adaptive immune response. One of them is calreticulin (CRT), an endoplasmic reticulum-associated chaperone. Its presence on the surface of dying tumor cells serves as an “eat me” signal for antigen presenting cells (APC). Engulfment of tumor cells by APCs results in the presentation of tumor’s antigens to cytotoxic T-cells and production of cytokines/chemokines, which activate immune cells responsible for tumor cells killing. Thus, the development of ICD and the expression of CRT can help standard therapy to eradicate tumor cells. Here, we review the physiological functions of CRT and its involvement in the ICD appearance in malignant disease. Moreover, we also focus on the ability of various anti-cancer drugs to induce expression of surface CRT on ovarian cancer cells. The second aim of this work is to discuss and summarize the prognostic/predictive value of CRT in ovarian cancer patients.

Role of an EpCAM auto-antibody in ovarian cancer patients with special regard to disseminated tumor cells in bone marrow

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16557-e16557
Author(s):  
M. Heubner ◽  
S. Kasimir-Bauer ◽  
D. Errico ◽  
D. Herlyn ◽  
R. Kimmig ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
Healthy Controls ◽  
Line Treatment ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
First Line Treatment

e16557 Background: EpCAM is a tumor associated antigen which is frequently expressed in ovarian cancer. Recently, an autoantibody (AAB) against EpCAM has been identified in ovarian cancer patients. Autoantibodies are immunogene factors and might be of prognostic importance. We showed that disseminated tumor cells (DTC) in bone marrow carry the EpCAM antigen on their surface and correlate with poorer progression free survival (PFS). Here, we evaluated whether EpCAM-AABs have an impact on clinical parameters or the presence of DTC in ovarian cancer patients. Methods: EpCAM-AABs were determined in sera of 28 healthy voluntary age matched females and 62 patients with primary epithelial ovarian cancer before and after platinum-based chemotherapy using a recombinant EpCAM-epitope for antibody- detection by ELISA technique. Mean follow up time was 13 months. DTC in BM were detected by immunocytochemistry applying the pan cytokeratin antibody A45-B/B3. All samples exceeding the mean antibody titer of healthy controls plus 2 standard deviations were considered positive. Results: The antibody titer of healthy controls was 0.061 + 0.015. Using a cut-off value of 0.091, we found 9/62 (15%) ovarian cancer patients to be positive for EpCAM-AABs after first-line treatment. Interestingly, no positive AAB-titers were seen before therapy. Using the paired T-Test, we noted a significant posttherapeutic increase of AABs (CI 0.95, p < 0.0001). Analysis of PFS, FIGO stage, resection status, grading, age, sensitivity to platinum based chemotherapy and DTC did not reveal significant associations with positive EpCAM-AAB titers. Conclusions: The clinical course of ovarian cancer patients and the prevalence of DTC were not altered by EpCAM-AABs. Interestingly, we observed an increase of antibody-levels after first-line treatment. For further validation, we intend to extend our patient collective. In future, it might also be interesting to investigate the impact of AABs on response to targeted therapies against EpCAM. No significant financial relationships to disclose.

In vitro assessment of dendritic cells pulsed with apoptotic tumor cells as a vaccine for ovarian cancer patients

2007 ◽  
Vol 122 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Zuzana Tobiásová ◽  
Dagmar Pospíšilová ◽  
Ashley M. Miller ◽  
Ivo Minárik ◽  
Klára Sochorová ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
In Vitro Assessment

Proliferative response of lymphocytes from ovarian cancer patients to autologous tumor cells

1988 ◽  
Vol 27 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Paola Allavena ◽  
Patrizia Lo Presti ◽  
Maria Di Bello ◽  
Valeria Lucchini ◽  
Andrea Lissoni ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Proliferative Response ◽  
Autologous Tumor
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