Glycomic-Based Biomarkers for Ovarian Cancer: Advances and Challenges

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.

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Potential Markers for Detection and Monitoring of Ovarian Cancer

Journal of Oncology ◽

10.1155/2011/475983 ◽

2011 ◽

Vol 2011 ◽

pp. 1-17 ◽

Cited By ~ 36

Author(s):

Brandon J. D. Rein ◽

Sajal Gupta ◽

Rima Dada ◽

Joelle Safi ◽

Chad Michener ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Detection ◽

Early Stage ◽

Survival Rates ◽

High Specificity ◽

Protein Markers ◽

Specificity And Sensitivity ◽

Novel Biomarkers ◽

New Biomarkers ◽

Current Screening

This paper reviews current screening techniques as well as novel biomarkers and their potential role in early detection of ovarian cancer. Ovarian cancer is one of the most common reproductive cancers and has the highest mortality rate amongst gynecologic cancers. Because most ovarian cancer diagnoses occur in the late stages of the disease, five-year survival rates fall below 20%. To improve survival rates and to lower mortality rates for ovarian cancer, improved detection at early stages of the disease is needed. Current screening approaches include tumor markers, ultrasound, or a combination. Efforts are underway to discover new biomarkers of ovarian cancer in order to surmount the obstacles in early-stage diagnosis. Among serum protein markers, HE4 and mesothelin can augment CA125 detection providing higher sensitivity and specificity due to the presence of these proteins in early-stage ovarian cancer. Detection testing that includes methylation of the MCJ gene and increased expression of vascular endothelial growth factor is correlated to poor prognosis and may predict patient survival outcome. Detection testing of biomarkers with long-term stability and combination panels of markers, will likely lead to effective screening strategies with high specificity and sensitivity for early detection of ovarian cancer.

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MOLECULAR AND GENETIC SUBTYPES OF OVARIAN CANCER: PROSPECTS FOR FURTHER STUDIES

Problems in oncology ◽

10.37469/0507-3758-2019-65-1-56-62 ◽

2019 ◽

Vol 65 (1) ◽

pp. 56-62

Author(s):

Alisa Villert ◽

Larisa Kolomiets ◽

Natalya Yunusova ◽

Yevgeniya Fesik

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Molecular Subtypes ◽

Survival Rates ◽

Consensus Algorithm ◽

Histopathological Diagnosis ◽

Low Grade ◽

High Grade ◽

Ovarian Carcinomas ◽

Genetic Subtypes

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

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Vaginal hysterectomy with or without bilateral salpingo-oophorectomy may be an alternative treatment for endometrial cancer patients with medical co-morbidities precluding standard surgical procedures: a systematic review

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000015 ◽

2019 ◽

Vol 29 (2) ◽

pp. 299-304 ◽

Cited By ~ 1

Author(s):

Arnold-Jan Kruse ◽

Henk G ter Brugge ◽

Harm H de Haan ◽

Hugo W Van Eyndhoven ◽

Hans W Nijman

Keyword(s):

Ovarian Cancer ◽

Endometrial Cancer ◽

Vaginal Hysterectomy ◽

Cancer Survival ◽

Survival Rates ◽

Survival Outcomes ◽

Ovarian Malignancy ◽

Post Menopausal ◽

Ovarian Cancer Survival ◽

Overall Survival Rates

ObjectiveVaginal hysterectomy with bilateral salpingo-oophorectomy may be an alternative strategy for patients with low-risk endometrial cancer and medical co-morbidities precluding laparoscopic or abdominal procedures. The current study evaluates the prevalence of co-existent ovarian malignancy in patients with endometrial cancer and the influence of bilateral salpingo-oophorectomy on survival outcomes in these patients.MethodsMedline and EMBASE were searched for studies published between January 1, 2000 and November 20, 2017 that investigated (1) the prevalence of co-existing ovarian malignancy (either metastases or primary synchronous ovarian cancer in women with endometrial cancer, and (2) the influence of bilateral salpingo-oophorectomy on recurrence and/or survival rates.ResultsOf the pre-menopausal and post-menopausal patients (n=6059), 373 were identified with metastases and 106 were identified with primary synchronous ovarian cancer. Of the post-menopausal patients (n=6016), 362 were identified with metastases and 44 were identified with primary synchronous ovarian cancer. Survival outcomes did not differ for pre-menopausal patients with endometrial cancer with and without bilateral salpingo-oophorectomy (5-year overall survival rates were 89–94.5% and 86–97.8%, respectively).ConclusionBilateral salpingo-oophorectomy during vaginal hysterectomy seems to have a limited impact on disease outcome in patients with endometrial cancer. These results support the view that vaginal hysterectomy alone or with bilateral salpingo-oophorectomy may be an option for patients with endometrial cancer who are not ideal surgical candidates.

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ISOLATED BENZODIAZEPINE TOXICITY AND THE USE OF FLUMAZENIL: AN EYE-OPENING ANTIDOTE CASE REPORT IN A TERTIARY CARE HOSPITAL

10.36106/gjra/2914895 ◽

2021 ◽

pp. 231-233

Author(s):

Siddharth Panikkar ◽

Gigy Varkey Kuruttukulam ◽

Manju Manmadhan ◽

Jithin Antony Bose ◽

Jacob Chacko ◽

...

Keyword(s):

Case Report ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Care Hospital ◽

Delay In Diagnosis ◽

Patient Medication ◽

Common Causes ◽

Eye Opening ◽

Ct Brain ◽

The 1960S

Since its debut in the 1960s, the broad use and availability of benzodiazepines has mirrored the increased incidence of overdose cases. Due to its non-specic presentation, there is often a delay in diagnosis. We report a case of Benzodiazepine toxicity in a 70-year-old man who presented to us in a comatose state. He was evaluated at another hospital initially and was intubated in view of his low Glasgow Coma scale. A CT brain plain study was done suspecting a basilar artery thrombus and he was referred to us for Neuro-Interventional procedures. As radiological, laboratory and electrophysiological investigations were unremarkable a provisional diagnosis of drug intoxication was made after patient medication review and a trial of Flumazenil was given, after which the patient had improved dramatically. Flumazenil is not routinely used due to fears of withdrawal seizures and its high cost. It also has no effect on reversing sedation caused by barbiturates, ethanol, or opioids. The antidote has a favorable risk-benet ratio when dosed appropriately and can be a helpful diagnostic tool after ruling out the more common causes of acute sensorium loss as demonstrated by this case report.

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Overexpression of centromere protein K (CENPK) in ovarian cancer is correlated with poor patient survival and associated with predictive and prognostic relevance

PeerJ ◽

10.7717/peerj.1386 ◽

2015 ◽

Vol 3 ◽

pp. e1386 ◽

Cited By ~ 9

Author(s):

Yi-Chao Lee ◽

Chi-Chen Huang ◽

Ding-Yen Lin ◽

Wen-Chang Chang ◽

Kuen-Haur Lee

Keyword(s):

Ovarian Cancer ◽

High Reliability ◽

Ovarian Cancer Cells ◽

Cancer Antigen 125 ◽

Centromere Protein ◽

Novel Biomarkers ◽

Cure Rates ◽

Cancer Tissues ◽

First Time

Ovarian cancer has a poor prognosis. Most patients are diagnosed with ovarian cancer when the disease has reached an advanced stage and cure rates are generally under 30%. Hence, early diagnosis of ovarian cancer is the best means to control the disease in the long term and abate mortality. So far, cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the gold-standard tumor markers for ovarian cancer; however, these two markers can be elevated in a number of conditions unrelated to ovarian cancer, resulting in decreased specifically and positive predictive value. Therefore, it is urgent to identify novel biomarkers with high reliability and sensitivity for ovarian cancer. In this study for the first time, we identified a member of the centromere protein (CENP) family, CENPK, which was specifically upregulated in ovarian cancer tissues and cell lines and the overexpression of which was associated with poor prognoses in patients with ovarian cancer. In addition, the presence of CENPK significantly improved the sensitivity of CA125 or HE4 for predicting clinical outcomes of ovarian cancer patients. In conclusion, we identified that CENPK was specifically upregulated in ovarian cancer cells and can be used as a novel tumor marker of ovarian cancer.

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Emerging Role of Inhibin as a Biomarker for Ovarian Cancer

Women s Health ◽

10.1517/17455057.1.1.051 ◽

2005 ◽

Vol 1 (1) ◽

pp. 51-57 ◽

Cited By ~ 1

Author(s):

David M Robertson ◽

Martin K Oehler

Keyword(s):

Ovarian Cancer ◽

Granulosa Cell ◽

Early Stage ◽

Clinical Stage ◽

Survival Rates ◽

Ovarian Carcinomas ◽

Gynecological Malignancy ◽

Granulosa Cell Tumors ◽

Ovarian Cancers ◽

Specificity And Sensitivity

Ovarian cancer is the most lethal gynecological malignancy as it is diagnosed at a late clinical stage in more than 80% of patients. The development of diagnostic tests that can detect all types of ovarian cancers with high specificity and sensitivity, and at an early stage would improve survival rates. Serum inhibin is an ovarian hormone involved in the regulation of fertility, decreasing to undetectable levels after menopause. Certain ovarian malignancies, such as mucinous carcinomas and granulosa cell tumors, continue to produce inhibin, which is detectable in serum. A test for serum inhibin has been developed which is able to diagnose granulosa cell tumors and mucinous carcinomas with high accuracy. When the inhibin assay is used in conjunction with the CA125 test, which detects epithelial ovarian carcinomas, the two tests detect the majority of ovarian cancers with high sensitivity (95%) and specificity (95%). This article discusses the application of the inhibin test in ovarian cancer.

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Molecular genetic changes in gastric carcinoma

International Journal of Molecular and Immuno Oncology ◽

10.25259/ijmio_8_2020 ◽

2021 ◽

Vol 6 ◽

pp. 30-46

Author(s):

Juhi Singh ◽

Puneet Kumar ◽

Khushi Verma ◽

Satyender Kumar Tiwary ◽

Gopeshwar Narayan ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Carcinoma ◽

Wide Spectrum ◽

Molecular Genetic ◽

Survival Rates ◽

High Throughput Analysis ◽

Genetic Changes ◽

Genetic Level ◽

New Biomarkers

Gastric cancer remains highly prevalent and accounts for a notable proportion of global cancer mortality and this is associated with poor survival rates. Understanding the molecular genetic changes of gastric carcinoma may offer an insight into its pathogenesis helps in identifying new biomarkers, aid prognostication, and novel treatment targets. Over a past few decades, advances in technology and high throughput analysis have improved understanding of the molecular genetic aspects of gastric cancer. In this article, hierarchy of the changes at genetic and molecular level including several aspects which are heterogenous and represents a wide spectrum such as tumor suppressor genes, oncogenes, cellcycle regulators, apoptosis, cell-adhesion molecules, loss of heterozygosity, microsatellite instability, and epigenetic changes. The classification of gastric carcinoma at molecular and genetic level as well as hereditary gastric carcinoma is elaborated. The molecular genetic aspects regarding pathogenesis, changes and aberrations of all genes and pathways which are involved in gastric cancer are addressed in this review.

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The Clinicopathologic Characteristics and 3-Year Survival Rates of Epithelial Ovarian Cancer in Iran During 2011-2017

International Journal of Women s Health and Reproduction Sciences ◽

10.15296/ijwhr.2019.82 ◽

2018 ◽

Vol 7 (4) ◽

pp. 496-500

Author(s):

Shahrzad Sheikh Hasani ◽

Mitra Modares Gilani ◽

Setareh Akhavan ◽

Azam-Sadat Mousavi ◽

Elham Saffarieh ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Survival Rate ◽

Epithelial Ovarian Cancer ◽

Mucinous Adenocarcinoma ◽

Survival Rates ◽

Newly Diagnosed ◽

Clinicopathologic Characteristics ◽

Cross Sectional ◽

Treatment Type

Objectives: The aim of this study was to determine the 3-year overall survival among the epithelial ovarian cancer patients based on the histology, age, and the stage of the disease in Iran during 2011-2017. Materials and Methods: This study was a cross-sectional retrospective study that was conducted on 179 newly diagnosed patients with epithelial ovarian cancer, who had referred to the gynecologic cancers clinic in a referral training hospital in Tehran during 2011-2017. The patients’ data including the demographic characteristics of the patients, the stage of the disease, and the treatment type were analyzed based on the pathologic responses. Results: Among 220 newly diagnosed patients with epithelial ovarian cancer, 179 of them were suitable for the follow-up. There were 93 death and 85 living cases among these patients and the mean age of the patients was 50.5 ± 11.3. In addition, most of the patients were in stage 3 (60.9%) and 6.7% of them were in stage 4. The most common pathology was serous adenocarcinoma (70.9%). In this study, the overall survival rate had no connection with the type of tumor histology but it was related to the stage of the disease (P=0.05). Finally, there was no mortality in stage one and among the mucinous adenocarcinoma cases. Conclusions: The survival in the epithelial ovarian cancer was related to the stage of the disease and among all the pathologies, mucinous adenocarcinoma and clear cell carcinoma had the best survival rate.

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Haemato- oncology and malignancy

Clinical Pharmacology for Prescribing ◽

10.1093/oso/9780199694938.003.0021 ◽

2019 ◽

Author(s):

Stevan R. Emmett ◽

Nicola Hill ◽

Federico Dajas-Bailador

Keyword(s):

Cancer Diagnosis ◽

Survival Rates ◽

Morbidity And Mortality ◽

Unknown Primary ◽

Diagnostic Strategies ◽

Diagnostic Skills ◽

The United Kingdom ◽

General Improvement ◽

After Cancer ◽

The Uk

Cancer is a common cause of morbidity and mortality in the United Kingdom (UK), affecting approximately two out of every five people during their lifetime. In 2015 there was an estimated 2.5 million people in the UK who had had a cancer diagnosis, an increase of almost half a million in the previous 5 years. The proportion of people living longer after cancer is increasing, and the number of people alive more than 5 years from initial diagnosis is predicted to more than double between 2010 and 2030 to 2.7 million. By the end of 2020, more than a thousand people would have been diagnosed with cancer every day in the UK. Cancer can affect all organs of the body with over 200 types identified. However, only a small number of cancer types account for most cases. Over half of all new diagnoses are due to four cancers (in order of frequency)— breast, prostate, lung, and bowel. In 2011 there were approximately 50 000 new diagnoses of breast cancer in the UK. The incidence of cancer diagnosis is increasing year on year, in part due to improving diagnostic skills, but also because of an increasing elderly population. Cancer of unknown primary origin accounts for about 3% of total cancers. Although UK statistics show a general improvement in the 5-year survival rates for the majority of common cancers, some have not shown any notable improvement. Survival is not only determined by the type of cancer, but also the age at diagnosis, stage, and co- morbidities such as heart, pulmonary, and renal disease, which can affect the treatment regimen. As well as this, certain cancers carry a significantly worse prognosis than others. For example, 10- year survival for pancreatic and lung cancer are 1% and 5%, respectively. In comparison, the 10- year survival for testicular cancer is over 98% and almost 90% in skin confined melanoma. Newer diagnostic strategies are expected to detect all cancers early, allowing prompt intervention, and improving both morbidity and mortality rates further. Cancer is a product of mutations in genes involved in controlling cell growth, differentiation, and death (apoptosis).

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MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16091510 ◽

2019 ◽

Vol 16 (9) ◽

pp. 1510 ◽

Cited By ~ 17

Author(s):

San-Nung Chen ◽

Renin Chang ◽

Li-Te Lin ◽

Chyi-Uei Chern ◽

Hsiao-Wen Tsai ◽

...

Keyword(s):

Ovarian Cancer ◽

Messenger Rna ◽

Cancer Biology ◽

Cancer Metastasis ◽

Female Reproductive System ◽

Future Perspectives ◽

Action Current ◽

Cellular Processes ◽

New Biomarkers ◽

Tumor Types

Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein.

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