CA125 and Ovarian Cancer: A Comprehensive Review

Ovarian cancer is the second most lethal gynecological malignancy. The tumour biomarker CA125 has been used as the primary ovarian cancer marker for the past four decades. The focus on diagnosing ovarian cancer in stages I and II using CA125 as a diagnostic biomarker has not improved patients’ survival. Therefore, screening average-risk asymptomatic women with CA125 is not recommended by any professional society. The dualistic model of ovarian cancer carcinogenesis suggests that type II tumours are responsible for the majority of ovarian cancer mortality. However, type II tumours are rarely diagnosed in stages I and II. The recent shift of focus to the diagnosis of low volume type II ovarian cancer in its early stages of evolution provides a new and valuable target for screening. Type II ovarian cancers are usually diagnosed in advanced stages and have significantly higher CA125 levels than type I tumours. The detection of low volume type II carcinomas in stage IIIa/b is associated with a higher likelihood for optimal cytoreduction, the most robust prognostic indicator for ovarian cancer patients. The diagnosis of type II ovarian cancer in the early substages of stage III with CA125 may be possible using a higher cutoff point rather than the traditionally used 35 U/mL through the use of point-of-care CA125 assays in primary care facilities. Rapid point-of-care testing also has the potential for effective longitudinal screening and quick monitoring of ovarian cancer patients during and after treatment. This review covers the role of CA125 in the diagnosis and management of ovarian cancer and explores novel and more effective screening strategies with CA125.

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Upregulation of cyclase-associated actin cytoskeleton regulatory protein 2 in epithelial ovarian cancer correlates with aggressive histologic types and worse outcomes

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa026 ◽

2020 ◽

Vol 50 (6) ◽

pp. 643-652 ◽

Cited By ~ 1

Author(s):

Masataka Adachi ◽

Yohei Masugi ◽

Ken Yamazaki ◽

Katsura Emoto ◽

Yusuke Kobayashi ◽

...

Keyword(s):

Ovarian Cancer ◽

Actin Cytoskeleton ◽

Epithelial Ovarian Cancer ◽

Cell Lines ◽

Regulatory Protein ◽

Control Cell ◽

Type I ◽

Type Ii ◽

Expression Levels ◽

Histologic Types

Abstract Objective Cyclase-associated actin cytoskeleton regulatory protein 2 (CAP2) regulates actin dynamics to control cell cycles and cell migration. CAP2 overexpression contributes to cancer progression in several tumor types; however, the role of CAP2 expression in ovarian cancer remains unclear. This study aimed to clarify the significance of CAP2 expression in epithelial ovarian tumor. Methods We evaluated CAP2 expression in ovarian cancer cell lines using quantitative real-time polymerase chain reaction, western blotting and immunocytochemistry and examined the effect of CAP2 silencing in migration and proliferation assays. CAP2 immunohistochemistry was conducted using tissue specimens from 432 ovarian carcinoma patients; a further 55 borderline and benign 65 lesions were analyzed. CAP2 expression levels were defined as low, intermediate or high, for correlation analysis with clinicopathological factors. Results CAP2 expression was significantly higher in cell lines from Type II ovarian cancer than in those in Type I, and knockdown of CAP2 showed decreased migration and proliferation. Higher levels of CAP2 expression in human tissues were associated with Type II histology, residual lesion, lymph node metastasis, ascites cytology and higher clinical stage. High CAP2 expression levels were observed in 26 (23.4%) of 111 Type II ovarian cancers and in 16 (5.0%) of 321 Type I cancers but not in any borderline or benign lesions. Multivariate analyses showed that CAP2 expression in ovarian cancer is an independent prognostic factor for recurrence-free survival (P = 0.019). Conclusion CAP2 expression is upregulated in aggressive histologic types of epithelial ovarian cancer and serves as a novel prognostic biomarker for patient survival.

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Toxoplasmosis among cancer patients undergoing chemotherapy: a population study based on the serological, molecular and epidemiological aspects

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/traa112 ◽

2020 ◽

Author(s):

Seyed Abdollah Hosseini ◽

Mehdi Sharif ◽

Shahabeddin Sarvi ◽

Ghasem Janbabai ◽

Shahrbanoo Keihanian ◽

...

Keyword(s):

Cancer Patients ◽

Fragment Length Polymorphism ◽

Type I ◽

Type Ii ◽

Genotype 1 ◽

Serum Samples ◽

Northern Iran ◽

Patients With Cancer ◽

Genotype 2 ◽

High Prevalence

Abstract Background Toxoplasmosis is highly prevalent in northern Iran and immunocompromised individuals are more susceptible to this infection. The present study aimed to determine the seroprevalence, parasitism and genetic diversity of Toxoplasma gondii among patients with cancer undergoing chemotherapy in northern Iran. Methods A total of 350 serum samples obtained from cancer patients were collected from laboratory centers in northern Iran. Immunodiagnosis and DNA detection were accomplished by ELISA and PCR. Thereafter, multiplex-nested PCR-restriction fragment length polymorphism was used for the genotyping of T. gondii. Results In general, out of 350 patients, 264 (75.4%) and 9 (2.57%) cases were positive for anti-T. gondii IgG and IgM, respectively. Moreover, 19 (5.43%) samples contained T. gondii DNA. From 19 positive samples, 10 high-quality samples with sharp and non-smear bands were selected to determine the genotypes of T. gondii. Accordingly, the samples were classified as genotype #1 (type II clonal; n=4, 40%), genotype #2 (type III clonal; n=3, 30%), genotype #10 (type I clonal; n=2, 20%) and genotype #27 (type I variant; n=1, 10%). Conclusions As evidenced by the results, due to the high prevalence of T. gondii, cancer patients in northern Iran are at serious risk of severe toxoplasmosis and its complications. Therefore, oncologists need to regard this critical health problem as a matter requiring urgent attention.

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Abstract 447: The presence and persistence of ERCC1 positive circulating tumor cells predicts worse prognosis in primary ovarian cancer patients

10.1158/1538-7445.am2016-447 ◽

2016 ◽

Author(s):

Issam Chebouti ◽

Paul Buderath ◽

Jan Dominik Kuhlmann ◽

Yvonne Bokeloh ◽

Siggi Hauch ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Primary Ovarian Cancer ◽

Worse Prognosis

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Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2013.07.094 ◽

2013 ◽

Vol 131 (1) ◽

pp. 52-58 ◽

Cited By ~ 40

Author(s):

Björg Kristjansdottir ◽

Kristina Levan ◽

Karolina Partheen ◽

Karin Sundfeldt

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Diagnostic Performance ◽

Type I ◽

Type Ii

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Are mesothelin and L1CAM useful biomarkers in primary ovarian cancer patients?

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.e15559 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. e15559-e15559

Author(s):

P. Wimberger ◽

S. Kasimir-Bauer ◽

B. Aktas ◽

R. Kimmig ◽

M. L. Heubner

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Primary Ovarian Cancer

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OC14.05: Clinical and ultrasound features of type I and type II epithelial ovarian cancer

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.12661 ◽

2013 ◽

Vol 42 (s1) ◽

pp. 28-29

Author(s):

J. Alcazar ◽

J. Utrilla-Layna ◽

J. Minguez ◽

M. Jurado

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Type I ◽

Type Ii ◽

Ultrasound Features

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Low expression of circular RNA hsa_circ_0078607 predicts poor prognosis in high-grade serous ovarian cancer

10.21203/rs.3.rs-121237/v1 ◽

2020 ◽

Author(s):

Nan Zhang ◽

Zhiyou Yang ◽

Yue Jin ◽

Shanshan Cheng ◽

Jiani Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Cancer Progression ◽

Poor Prognosis ◽

Cox Regression ◽

Prognostic Indicator ◽

High Grade ◽

Serous Ovarian Cancer ◽

Diagnosis And Prognosis ◽

Low Expression

Abstract Background Ovarian cancer remains one of the most lethal malignancies in women which is typically diagnosed at a late stage and has no effective screening strategy. It is essential to explore novel biomarkers for the diagnosis and prognosis of ovarian cancer, as well as therapeutic targets. Recent studies have shown that circRNAs participate in ovarian cancer progression by regulating various processes and being able to act as potential biomarkers for ovarian cancer diagnosis and prognosis. In the present study we aimed to explore the prognostic role of circ_0078607 in high-grade serous ovarian cancer. Results The expression of circ_0078607 in 49 high-grade serous ovarian cancer and adjacent non-cancerous tissue samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We noticed that circ_0078607 expression was significantly downregulated in ovarian cancer tissues compared with adjacent non-cancerous tissues. Besides, patients with low circ_0078607 expression exhibited parameters associated with poor prognosis, including advanced FIGO stage and higher serum CA125 level. Kaplan-Meier survival curve analysis showed that both progression-free survival and overall survival were significantly shortened in patients with low circ_0078607 expression. Cox regression model analysis showed that low expression of circ_0078607 was an adverse prognostic indicator for high-grade serous ovarian cancer patients. Conclusions Low expression of circ_0078607 might be an adverse prognostic indicator for high-grade serous ovarian cancer patients.

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Suicide and Accidental Death Among Women with Primary Ovarian Cancer: A population-based study

10.22541/au.162046313.31616020/v1 ◽

2021 ◽

Author(s):

Ying Chen ◽

Kaixu Yu ◽

Qingqing Zhu ◽

Weicheng Tang ◽

Dan Chen ◽

...

Keyword(s):

Ovarian Cancer ◽

General Population ◽

Epithelial Ovarian Cancer ◽

Pelvic Exenteration ◽

Type I ◽

Type Ii ◽

Accidental Death ◽

Cancer Data ◽

Standardized Mortality Ratios ◽

End Results

Objective To determine the relative risk of suicide and accidental death among patients with ovarian cancer to that of the general population, and to identify risk factors associated with suicide and accidental death. Design The surveillance, epidemiology, and end results (SEER) registry provided ovarian cancer data from 18 registries. Setting Surveillance, Epidemiology, and End Results database. Population The study population comprised 149,204 patients. Methods The standardized mortality ratios (SMRs) were calculated and Fine-Gray models were fitted, with stratifications on demographic and tumor-related characteristics. Main outcome measures The standardized mortality ratios. Results Women with ovarian cancer had a higher risk of suicide and accidental death than the cancer-free group (SMR=1.86; 95% CI [1.54-2.25] and SMR=1.54; 95% CI [1.39-1.71]). Subgroup analysis indicated that only patients with type II epithelial ovarian cancer (SMR=2.31; 95% CI [1.83-2.91]) had an increased risk of suicide, and those with type I and type II epithelial ovarian cancer (SMR=1.65; 95% CI [1.39-1.97] and SMR=1.49; 95% CI [1.30-1.70]) were at a higher risk of accidental death. Patients with ovarian cancer who were younger, white, diagnosed with high-grade, non-metastatic cancer and pelvic exenteration were at a higher risk of suicide. Additionally, pelvic exenteration increased the risk of suicide but not the risk of accidental death among these women. Conclusion Women with ovarian cancer had a higher risk of suicide and accidental death compared with the general population. Clinicians should identify high-risk subgroups of ovarian cancer patients for suicide and accidental death as early as possible, with appropriate prevention strategies.

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Integrated Analysis of Ferroptosis-Related Biomarker Signatures to Improve the Diagnosis and Prognosis Prediction of Ovarian Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.807862 ◽

2022 ◽

Vol 9 ◽

Author(s):

Huan Wang ◽

Qi Cheng ◽

Kaikai Chang ◽

Lingjie Bao ◽

Xiaofang Yi

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Cancer Patients ◽

Risk Group ◽

High Risk Group ◽

The Cancer Genome Atlas ◽

Integrated Analysis ◽

M2 Macrophage ◽

Gynecological Malignancy

Ovarian cancer remains the most lethal gynecological malignancy. Ferroptosis, a specialized form of iron-dependent, nonapoptotic cell death, plays a crucial role in various cancers. However, the contribution of ferroptosis to ovarian cancer is poorly understood. Here, we characterized the diagnostic, prognostic, and therapeutic value of ferroptosis-related genes in ovarian cancer by analyzing transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus databases. A reliable 10-gene ferroptosis signature (HIC1, ACSF2, MUC1, etc.) for the diagnosis of ovarian cancer was identified. Notably, we constructed and validated a novel prognostic signature including three FRGs: HIC1, LPCAT3, and DUOX1. We also further developed a risk score model based on these three genes which divided ovarian cancer patients into two risk groups. Functional analysis revealed that immune response and immune-related pathways were enriched in the high-risk group. Meanwhile, the tumor microenvironment was distinct between the two groups, with more M2 Macrophage infiltration and higher expression of key immune checkpoint molecules in the high-risk group than in the other group. Low-risk patients exhibited more favorable immunotherapy and chemotherapy responses. We conclude that crosstalk between ferroptosis and immunity may contribute to the worse prognosis of patients in the high-risk group. In particular, HIC1 showed both diagnostic and prognostic value in ovarian cancer. In vitro experiments demonstrated that inhibition of HIC1 improved drug sensitivity of chemotherapy and immunotherapy agents by inducing ferroptosis. Our findings provide new insights into the potential role of FRGs in the early detection, prognostic prediction, and individualized treatment decision-making for ovarian cancer patients.

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