Diagnostics

Research

Jump to: Review

10 pages, 1104 KiB

Open AccessArticle

Chondroitin Sulfate Disaccharides, a Serum Marker for Primary Serous Epithelial Ovarian Cancer

by Karina Biskup, Caroline Stellmach, Elena Ioana Braicu, Jalid Sehouli and Véronique Blanchard

Diagnostics 2021, 11(7), 1143; https://doi.org/10.3390/diagnostics11071143 - 23 Jun 2021

Cited by 5 | Viewed by 2073

Abstract

Glycosaminoglycans are long polysaccharidic chains, which are mostly present in connective tissues. Modified GAG expression in tissues surrounding malignant cells has been shown to contribute to tumor progression, aggressive status and metastasis in many types of cancer. Ovarian cancer is one of the [...] Read more.

Glycosaminoglycans are long polysaccharidic chains, which are mostly present in connective tissues. Modified GAG expression in tissues surrounding malignant cells has been shown to contribute to tumor progression, aggressive status and metastasis in many types of cancer. Ovarian cancer is one of the most lethal gynecological malignancies due to its late diagnosis because of the absence of clear symptoms and unavailability of early disease markers. We investigated for the first time GAG changes at the molecular level as a novel biomarker for primary epithelial ovarian cancer. To this end, serum of a cohort of 68 samples was digested with chondroitinase ABC, which releases chondroitin sulfate into disaccharides. After labeling and purification, they were measured by HPLC, yielding a profile of eight disaccharides. We proposed a novel GAG-based score named “CS- bio” from the measured abundance of disaccharides present that were of statistical relevance. CS-bio’s performance was compared with CA125, the clinically used serum tumor marker in routine diagnostics. CS-bio had a better sensitivity and specificity than CA125. It was more apt in differentiating early-stage patients from healthy controls, which is of high interest for oncologists. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

13 pages, 2852 KiB

Open AccessArticle

Evaluation of the Potential Diagnostic Utility of the Determination of Selected Caspases—Markers Involved in the Regulation of Apoptosis—In Patients with Ovarian Cancer

by Aleksandra Mielczarek-Palacz, Sylwia Jasińska and Anna Strzelec

Diagnostics 2021, 11(4), 704; https://doi.org/10.3390/diagnostics11040704 - 14 Apr 2021

Cited by 1 | Viewed by 2007

Abstract

Ovarian cancer remains a major diagnostic and therapeutic problem in modern gynecological oncology. For this reason, research which focuses on the search for new diagnostic markers and the assessment of their possible usefulness in clinical practice is still being conducted. The aim of [...] Read more.

Ovarian cancer remains a major diagnostic and therapeutic problem in modern gynecological oncology. For this reason, research which focuses on the search for new diagnostic markers and the assessment of their possible usefulness in clinical practice is still being conducted. The aim of this study was to evaluate serum levels of caspase-3, caspase-8, and caspase-9 in women with ovarian cancer. Patients with ovarian serous cystadenoma (Cystadenoma serosum) and papillary serous cystadenocarcinoma (Cystadenocarcinoma papillare serosum IIIC) were included in the study, as well as healthy women who constituted the control group. The results of the study revealed a statistically significantly decreased mean serum levels of caspase-3, caspase-8, and caspase-9 in women with ovarian cancer as compared to the control group (p ˂ 0.001), which indicates the involvement of the studied parameters in immune system disturbances occurring in the process of apoptosis by the extrinsic and intrinsic pathway and may be one of the mechanisms of immunosuppression accompanying these tumors. Determination of serum levels of examined caspases and CA 125 antigen in women with ovarian cancer in combination with other markers may prove useful in the future in the diagnosis of ovarian cancer, but this requires further studies. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

10 pages, 262 KiB

Open AccessArticle

Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

by Iolia Akaev, Siavash Rahimi, Olubukola Onifade, Francis John Edward Gardner, David Castells-Rufas, Eleanor Jones, Shyamika Acharige and Chit Cheng Yeoh

Diagnostics 2021, 11(3), 547; https://doi.org/10.3390/diagnostics11030547 - 19 Mar 2021

Cited by 2 | Viewed by 2129

Abstract

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were [...] Read more.

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

11 pages, 23455 KiB

Open AccessArticle

Prognostic Value of TNFR2 and STAT3 among High-Grade Serous Ovarian Cancer Survivors According to Platinum Sensitivity

by Janisha Silva Raju, Nor Haslinda Abd. Aziz, Ghofraan Abdulsalam Atallah, Chew Kah Teik, Mohamad Nasir Shafiee, Muhammad Fakhri Mohd Saleh, Ravichandran Jeganathan, Reena Rahayu Md Zin and Nirmala Chandralega Kampan

Diagnostics 2021, 11(3), 526; https://doi.org/10.3390/diagnostics11030526 - 16 Mar 2021

Cited by 3 | Viewed by 1735

Abstract

This study’s goal was to determine the protein expression level of tumour necrosis factor receptor 2 (TNFR2) and signal transducer and activator of transcription 3 (STAT3) in high-grade serous ovarian cancer (HGSC) tissues in relation to the platinum-based chemotherapy response and the prognosis [...] Read more.

This study’s goal was to determine the protein expression level of tumour necrosis factor receptor 2 (TNFR2) and signal transducer and activator of transcription 3 (STAT3) in high-grade serous ovarian cancer (HGSC) tissues in relation to the platinum-based chemotherapy response and the prognosis outcome. A total of 25 HGSC patients underwent primary surgical debulking followed by first-line adjuvant platinum-based chemotherapy. Tissue microarray (TMA) slides were constructed utilising archived formalin fixed paraffin embedded (FFPE). The protein expression of TNFR2 and STAT3 were analysed using immunohistochemistry (IHC) staining and subsequently were correlated to the clinicopathological characteristics, platinum sensitivity as well as the duration of progression-free survival. About 14 out of 25 patients (56.0%) were platinum-sensitive. The progression free survival was significantly longer in the platinum-sensitive (PS) group when compared to those with the platinum-resistant group (PR), p = 0.0001. Among patients with TNFR2 strong expression on ovarian tissue, there was a significantly longer progression-free survival interval of 540 days in the PS group compared to PR, p = 0.0001. Patients with STAT3 expression also showed significantly better progression-free survival of 660 days in the PS group when compared to the PR group, p = 0.0001. In conclusion, patients with strong TNFR2 and STAT3 expression in the ovarian tissue had significantly longer progression-free survival interval in the PS group. Nevertheless, further research with a larger number of tissues may be required to demonstrate further significant differences. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

15 pages, 2394 KiB

Open AccessArticle

Preclinical Evaluation of Artesunate as an Antineoplastic Agent in Ovarian Cancer Treatment

by Anthony McDowell, Jr., Kristen S. Hill, Joseph Robert McCorkle, Justin Gorski, Yilin Zhang, Ameen A. Salahudeen, Fred Ueland and Jill M. Kolesar

Diagnostics 2021, 11(3), 395; https://doi.org/10.3390/diagnostics11030395 - 26 Feb 2021

Cited by 16 | Viewed by 5210

Abstract

Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment. Methods: Standard cell culture technique [...] Read more.

Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment. Methods: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq analysis was utilized to identify genes and the associated genetic pathways that were differentially regulated in artesunate resistant organoid models compared to organoids that were sensitive to artesunate. Results: Artesunate treatment reduces cell viability in 2D and 3D ovarian cancer cell models. Clinically relevant concentrations of artesunate induce G1 arrest, but do not induce DNA damage. Pathways related to cell cycle progression, specifically G1/S transition, are upregulated in ovarian organoid models that are innately more resistant to artesunate compared to more sensitive models. Depending on the sequence of administration, the addition of artesunate to carboplatin and paclitaxel improves their effectiveness. Conclusions: Artesunate has preclinical activity in ovarian cancer that merits further investigation to treat ovarian cancer. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

16 pages, 4530 KiB

Open AccessArticle

Comprehensive Analysis of the Expression of Key Genes Related to Hippo Signaling and Their Prognosis Impact in Ovarian Cancer

by Paul Kubelac, Cornelia Braicu, Lajos Raduly, Paul Chiroi, Andreea Nutu, Roxana Cojocneanu, Liviuta Budisan, Ioana Berindan-Neagoe and Patriciu Achimas-Cadariu

Diagnostics 2021, 11(2), 344; https://doi.org/10.3390/diagnostics11020344 - 19 Feb 2021

Cited by 5 | Viewed by 2601

Abstract

The Hippo signaling pathway, one of the most conserved in humans, controlling dimensions of organs and tumor growth, is frequently deregulated in several human malignancies, including ovarian cancer (OC). The alteration of Hippo signaling has been reported to contribute to ovarian carcinogenesis and [...] Read more.

The Hippo signaling pathway, one of the most conserved in humans, controlling dimensions of organs and tumor growth, is frequently deregulated in several human malignancies, including ovarian cancer (OC). The alteration of Hippo signaling has been reported to contribute to ovarian carcinogenesis and progression. However, the prognostic roles of individual Hippo genes in OC patients remain elusive. Herein we investigated the expression level and prognostic value of key Hippo genes in OC using online databases, followed by a qRT-PCR validation step in an additional patient cohort. Using the GEPIA database, we observed an increased level for TP53 and reduced expression level for LATS1, LATS2, MST1, TAZ, and TEF in tumor tissue versus normal adjacent tissue. Moreover, LATS1, LATS2, TP53, TAZ, and TEF expression levels have prognostic significance correlated with progression-free survival. The qRT-PCR validation step was conducted in an OC patient cohort comprising 29 tumor tissues and 20 normal adjacent tissues, endorsing the expression level for LATS1, LATS2, and TP53, as well as for two of the miRNAs targeting the TP53 gene, revealing miR-25-3p upregulation and miR-181c-5p downregulation. These results display that there are critical prognostic value dysregulations of the Hippo genes in OC. Our data demonstrate the major role the conserved Hippo pathway presents in tumor control, underlying potential therapeutic strategies and controlling several steps modulated by miRNAs and their target genes that could limit ovarian cancer progression. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

9 pages, 777 KiB

Open AccessArticle

The Prognostic Relevance of Poly (ADP-Ribose) Polymerase Expression in Ovarian Cancer Tissue of Wild Type and BRCA-Mutation Carrier Patients

by Szabolcs Molnár, Beáta Vida, Lívia Beke, Gábor Méhes and Róbert Póka

Diagnostics 2021, 11(1), 144; https://doi.org/10.3390/diagnostics11010144 - 19 Jan 2021

Cited by 3 | Viewed by 2070

Abstract

(1) Background: The mechanism of platinum resistance in ovarian cancer is not fully clarified, but the properly functioning DNA repair mechanism can counteract the effect of conventional anticancer treatment. The objective of our study was to evaluate the expression of an important DNA [...] Read more.

(1) Background: The mechanism of platinum resistance in ovarian cancer is not fully clarified, but the properly functioning DNA repair mechanism can counteract the effect of conventional anticancer treatment. The objective of our study was to evaluate the expression of an important DNA repair enzyme, the Poly (ADP-Ribose) Polymerase (PARP) expression in epithelial ovarian cancer (EOC) tissues depending on BRCA status and to assess its relationship with platinum resistance. (2) Methods: Immunostaining to highlight PARP protein expression was performed using a rabbit polyclonal anti-PARP antibody. The intensity and distribution of immunostaining were assessed by light. Somatic BRCA1 or BRCA2 mutation carriers were identified with bidirectional sequencing of DNA from archived tumor tissue, if the test could not be performed due to technical reasons from tumor cells, the sequencing was done from peripheral blood cells to identify germline mutation carriers. The median progression-free survival (PFS) was generated for each semiquantitative group of PARP expression among chemotherapy-naive cases at the time of PARP immunohistochemistry. (3) Results: In the overall population, negative PARP immunohistochemistry predicted significant PFS (20.1 vs. 11.9 months, p = 0.001) and OS (49 vs. 114 months, p = 0.014) benefit. Genotype-stratified subgroup analysis in BRCA-negative cases confirmed the role of PARP positivity indicating an unfavorable prognosis in the entire population (relapsed 73.91% vs. 92%; OR: 4.06; p = 0.04). In the cases of the subgroup carrying the BRCA mutation, the presence of PARP expression was not associated with less favorable relapse rates, but with marginal significance for overall survival predicted a lower chance of survival (OS more than 32 months 72.73% vs. 35%; OR: 0.2; p = 0.05). (4) Conclusion: The BRCA wild type patients with strong expression of PARP enzymes before the first set of chemotherapy have a poor prognosis. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

Review

Jump to: Research

16 pages, 603 KiB

Open AccessReview

Glycomic-Based Biomarkers for Ovarian Cancer: Advances and Challenges

by Francis Mugeni Wanyama and Véronique Blanchard

Diagnostics 2021, 11(4), 643; https://doi.org/10.3390/diagnostics11040643 - 1 Apr 2021

Cited by 19 | Viewed by 3115

Abstract

Ovarian cancer remains one of the most common causes of death among gynecological malignancies afflicting women worldwide. Among the gynecological cancers, cervical and endometrial cancers confer the greatest burden to the developing and the developed world, respectively; however, the overall survival rates for [...] Read more.

Ovarian cancer remains one of the most common causes of death among gynecological malignancies afflicting women worldwide. Among the gynecological cancers, cervical and endometrial cancers confer the greatest burden to the developing and the developed world, respectively; however, the overall survival rates for patients with ovarian cancer are worse than the two aforementioned. The majority of patients with ovarian cancer are diagnosed at an advanced stage when cancer has metastasized to different body sites and the cure rates, including the five-year survival, are significantly diminished. The delay in diagnosis is due to the absence of or unspecific symptoms at the initial stages of cancer as well as a lack of effective screening and diagnostic biomarkers that can detect cancer at the early stages. This, therefore, provides an imperative to prospect for new biomarkers that will provide early diagnostic strategies allowing timely mitigative interventions. Glycosylation is a protein post-translational modification that is modified in cancer patients. In the current review, we document the state-of-the-art of blood-based glycomic biomarkers for early diagnosis of ovarian cancer and the technologies currently used in this endeavor. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

20 pages, 1239 KiB

Open AccessReview

New Predictive Biomarkers for Ovarian Cancer

by Ghofraan Abdulsalam Atallah, Nor Haslinda Abd. Aziz, Chew Kah Teik, Mohamad Nasir Shafiee and Nirmala Chandralega Kampan

Diagnostics 2021, 11(3), 465; https://doi.org/10.3390/diagnostics11030465 - 7 Mar 2021

Cited by 48 | Viewed by 6447

Abstract

Ovarian cancer is the eighth-most common cause of death among women worldwide. In the absence of distinctive symptoms in the early stages, the majority of women are diagnosed in advanced stages of the disease. Surgical debulking and systemic adjuvant chemotherapy remain the mainstays [...] Read more.

Ovarian cancer is the eighth-most common cause of death among women worldwide. In the absence of distinctive symptoms in the early stages, the majority of women are diagnosed in advanced stages of the disease. Surgical debulking and systemic adjuvant chemotherapy remain the mainstays of treatment, with the development of chemoresistance in up to 75% of patients with subsequent poor treatment response and reduced survival. Therefore, there is a critical need to revisit existing, and identify potential biomarkers that could lead to the development of novel and more effective predictors for ovarian cancer diagnosis and prognosis. The capacity of these biomarkers to predict the existence, stages, and associated therapeutic efficacy of ovarian cancer would enable improvements in the early diagnosis and survival of ovarian cancer patients. This review not only highlights current evidence-based ovarian-cancer-specific prognostic and diagnostic biomarkers but also provides an update on various technologies and methods currently used to identify novel biomarkers of ovarian cancer. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

13 pages, 819 KiB

Open AccessReview

MUTYH as an Emerging Predictive Biomarker in Ovarian Cancer

by Megan L. Hutchcraft, Holly H. Gallion and Jill M. Kolesar

Diagnostics 2021, 11(1), 84; https://doi.org/10.3390/diagnostics11010084 - 6 Jan 2021

Cited by 15 | Viewed by 5678

Abstract

Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog (MUTYH) are best known for MUTYH associated polyposis and colorectal cancer, it plays a [...] Read more.

Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog (MUTYH) are best known for MUTYH associated polyposis and colorectal cancer, it plays a role in the development of ovarian cancer. In this review, we discuss the function of the MUTYH gene, mutation epidemiology, and its mechanism for carcinogenesis. We additionally examine its emerging role in the development of ovarian cancer and how it may be used as a predictive and targetable biomarker. MUTYH mutations may confer the risk of ovarian cancer by the failure of its well-known base excision repair mechanism or by failure to induce cell death. Biallelic germline MUTYH mutations confer a 14% risk of ovarian cancer by age 70. A monoallelic germline mutation in conjunction with a somatic MUTYH mutation may also contribute to the development of ovarian cancer. Resistance to platinum-based chemotherapeutic agents may be seen in tumors with monoallelic mutations, but platinum sensitivity in the biallelic setting. As MUTYH is intimately associated with targetable molecular partners, therapeutic options for MUTYH driven ovarian cancers include programed-death 1/programed-death ligand-1 inhibitors and poly-adenosine diphosphate ribose polymerase inhibitors. Understanding the function of MUTYH and its associated partners is critical for determining screening, risk reduction, and therapeutic approaches for MUTYH-driven ovarian cancers. Full article

(This article belongs to the Special Issue New Predictive Biomarkers for Ovarian Cancer)

► Show Figures

Figure 1

Journal Menu

Journal Browser

New Predictive Biomarkers for Ovarian Cancer

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (10 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI