A Novel Predictive Tool for Discriminating Endometriosis Associated Ovarian Cancer from Ovarian Endometrioma: The R2 Predictive Index

Background: Magnetic resonance (MR) relaxometry provides a noninvasive tool to discriminate between ovarian endometrioma (OE) and endometriosis-associated ovarian cancer (EAOC), with a sensitivity and specificity of 86% and 94%, respectively. MRI models that can measure R2 values are limited, and the R2 values differ between MRI models. This study aims to extract the factors contributing to the R2 value, and to make a formula for estimating the R2 values, and to assess whether the R2 predictive index calculated by the formula could discriminate EAOC from OE. Methods: This retrospective study was conducted at our institution from November 2012 to February 2019. A total of 247 patients were included in this study. Patients with benign ovarian tumors mainly received laparoscopic surgery, and the patients suspected of having malignant tumors underwent laparotomy. Information from a chart review of the patients’ medical records was collected. Results: In the investigative cohort, among potential factors correlated with the R2 value, multiple regression analyses revealed that tumor diameter and CEA could predict the R2 value. In the validation cohort, multivariate analysis confirmed that age, CRP, and the R2 predictive index were the independent factors. Conclusions: The R2 predictive index is useful and valuable to the detection of the malignant transformation of endometrioma.

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FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.

Endocrine Related Cancer ◽

10.1677/erc.0.0110315 ◽

2004 ◽

Vol 11 (2) ◽

pp. 315-321 ◽

Cited By ~ 23

Author(s):

I Rzepka-G√≥rska ◽

A Chudecka-G≈Çaz ◽

B Kosmowska

Keyword(s):

Ovarian Cancer ◽

Differential Diagnosis ◽

Malignant Tumors ◽

Ovarian Tumors ◽

Predictive Values ◽

Epithelial Tumors ◽

Ovarian Carcinogenesis ◽

Benign Ovarian Tumors ◽

Sensitivity Specificity

The aim of this work was to compare mean concentrations of gonadotropins in serum and fluid from malignant and benign ovarian tumors. We enrolled 126 patients diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors (n=14), benign cystadenomas (n=28) and simple cysts (n=44) of the ovary. Premenopausal and postmenopausal subgroups were formed in each group. The concentration of FSH and LH was measured in serum and tumor fluid and the serum/tumor fluid ratio was calculated. The results in each group were compared and the sensitivity, specificity, positive and negative predictive values were determined. Mean concentrations of both gonadotropins in ovarian cancer fluid were significantly higher than in the remaining groups (P ranged from <0.005 to <0.0001). Mean serum/fluid ratios were lowest in ovarian cancer (FSH=2.91, LH=4.19). Our findings support the hypothesis that gonadotropins are involved in ovarian carcinogenesis and suggest that gonadotropin serum/tumor fluid ratios could be of value in the differential diagnosis of functional and organic cysts of the ovary.

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ROLE OF ULTRASOUND IN THE DETECTION OF RECURRENT OVARIAN CANCER

UZBEK MEDICAL JOURNAL ◽

10.26739/2181-0664-2020-6-4 ◽

2020 ◽

Vol 6 (1) ◽

pp. 23-31

Author(s):

M. Alisherova ◽

◽

M. Ismailova

Keyword(s):

Ovarian Cancer ◽

Surgical Treatment ◽

Reproductive System ◽

Malignant Tumors ◽

Recurrent Ovarian Cancer ◽

Primary Diagnosis ◽

Female Reproductive System

Currently, there are no standard approaches to monitoring patients with ovarian cancer (OC). While the role of ultrasound (US) has been identified in the primary diagnosis of OS, it is still controversial during the subsequent surgical treatment of OC. In world statistics, ovarian cancer is consistently among the four main localizations of malignant tumors of the female reproductive system, along with tumors of the breast, body and cervix.

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A prospective observational study on the effectiveness of risk of malignancy index score (RMI 3) in a tertiary care centre in Eastern India

Asian Journal of Medical Sciences ◽

10.3126/ajms.v11i5.29548 ◽

2020 ◽

Vol 11 (5) ◽

pp. 54-60

Author(s):

Apurba Mandal ◽

Shibram Chattopadhyay ◽

Sushanta Mondal ◽

Arunava Biswas

Keyword(s):

Ovarian Cancer ◽

Adnexal Mass ◽

Malignant Tumors ◽

Histopathological Examination ◽

Tertiary Care ◽

Ca 125 ◽

Tertiary Care Centre ◽

Gynecology And Obstetrics ◽

Risk Of Malignancy ◽

Malignant Lesions

Background: Adnexal mass is a common presentation in today’s gynecological practice. The incidence of ovarian cancer is increasing day by day and diagnosis is often difficult to be made pre operatively with inadequate surgical exploration is a regular occurrence. Aims and Objectives: To assess and validate the importance of RMI-3 score as pre-operative diagnostic tool of differentiating benign from malignant adnexal mass for starting first line therapy of ovarian cancer and to find out the incidences of ovarian malignancy among study population. Material and Methods: The study was conducted in the Department of Gynecology and Obstetrics on (n=115) patients attending GOPD and indoor with adnexal mass fulfilling the inclusion and exclusion criteria using purposive sampling technique. All the selected cases underwent ultrasonography and serum CA- 125 level estimation necessary for calculating RMI score. A score of >200 was taken as suggestive of malignancy and confirmatory diagnosis was performed by histopathological examination obtained from staging laparotomy of adnexal mass. The individual scores were then correlated with final outcomes with statistical analyses. Results: The study revealed benign ovarian tumors are more under 50 years (78.46%) and patients with normal BMI are diagnosed with maximum of malignancy (n = 28). History of tubal ligation carried less risk of malignancy (p<0.0001). Histologically malignant tumors found mostly in 71.4% postmenopausal group whereas 94.1% benign pathology were present in perimenopausal group and there is no association found between parity and histopathology (p=0.058). Bilateral (p=0.013), multilocular (p=0.000) tumors with solid areas (p<0.0001) and thick papillary projections (p<0.0001) had statistically significant association with malignant lesions. RMI score (>200) had more efficacy than serum CA-125 level (>46) in differentiating malignant lesions from benign one in terms of specificity (96% vs 83.87%) and positive predictive value (95% vs 79.17%). Conclusions: RMI-3 score is a simple, reliable and effective tool in differentiating benign from malignant adnexal masses thereby help in quick referral and management of cases with increase chances of survival of the patients.

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Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2

Cell Death and Disease ◽

10.1038/s41419-021-03581-3 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Shourong Wang ◽

Zixiang Wang ◽

Jieyin Li ◽

Junchao Qin ◽

Jianping Song ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Malignant Tumors ◽

Splicing Factor ◽

Ovarian Cancer Cells ◽

Nuclear Speckles ◽

Aberrant Expression ◽

Intergenic Regions

AbstractAberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5′ and 3′ splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.

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A novel decision tree model based on chromosome imbalances in cell-free DNA and CA-125 in the differential diagnosis of ovarian cancer

The International Journal of Biological Markers ◽

10.1177/1724600821992356 ◽

2021 ◽

pp. 172460082199235

Author(s):

Weina Zhang ◽

Yu-min Zhang ◽

Yuan Gao ◽

Shengmiao Zhang ◽

Weixin Chu ◽

...

Keyword(s):

Ovarian Cancer ◽

Differential Diagnosis ◽

Decision Tree ◽

Copy Number ◽

Malignant Tumors ◽

Copy Number Variations ◽

Ca 125 ◽

Benign Tumors ◽

Cell Free Dna ◽

Free Dna

Objective: CA-125 is widely used as biomarker of ovarian cancer. However, CA-125 suffers low accuracy. We developed a hybrid analytical model, the Ovarian Cancer Decision Tree (OCDT), employing a two-layer decision tree, which considers genetic alteration information from cell-free DNA along with CA-125 value to distinguish malignant tumors from benign tumors. Methods: We consider major copy number alterations at whole chromosome and chromosome-arm level as the main feature of our detection model. Fifty-eight patients diagnosed with malignant tumors, 66 with borderline tumors, and 10 with benign tumors were enrolled. Results: Genetic analysis revealed significant arm-level imbalances in most malignant tumors, especially in high-grade serous cancers in which 12 chromosome arms with significant aneuploidy ( P<0.01) were identified, including 7 arms with significant gains and 5 with significant losses. The area under receiver operating characteristic curve (AUC) was 0.8985 for copy number variations analysis, compared to 0.8751 of CA125. The OCDT was generated with a cancerous score (CScore) threshold of 5.18 for the first level, and a CA-125 value of 103.1 for the second level. Our most optimized OCDT model achieved an AUC of 0.975. Conclusions: The results suggested that genetic variations extracted from cfDNA can be combined with CA-125, and together improved the differential diagnosis of malignant from benign ovarian tumors. The model would aid in the pre-operative assessment of women with adnexal masses. Future clinical trials need to be conducted to further evaluate the value of CScore in clinical settings and search for the optimal threshold for malignancy detection.

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Stem-like tumor cells and proinflammatory cytokines in the ascitic fluid of ovarian cancer patients

Russian Clinical Laboratory Diagnostics ◽

10.51620/0869-2084-2021-66-5-297-303 ◽

2021 ◽

Vol 66 (5) ◽

pp. 297-303

Author(s):

S. O. Gening ◽

T. V. Abakumova ◽

I. I. Antoneeva ◽

A. A. Rizvanov ◽

T. P. Gening ◽

...

Keyword(s):

Ovarian Cancer ◽

Blood Serum ◽

Tumor Cells ◽

Ascitic Fluid ◽

Early Stage ◽

Abdominal Cavity ◽

Disease Stage ◽

Cell Populations ◽

Benign Ovarian Tumors ◽

Number Of Cells

Ovarian cancer (OC) is able to develop implantation metastases in the abdominal cavity. Ascites is potentially useful for evaluating cancer features. The aim of the study was to assess the content of stem-like tumor cells and inflammatory mediators in ascites of OC. The prospective study included 11 patients with primary OC having ascites, 8 patients with benign ovarian tumors having ascites and 22 healthy women. In ascitic fluid obtained by laparocentesis, the populations of tumor stem-like cells were determined on a Cytoflex S` flow cytometer (Beckman Coulter, USA) and CytExpert Software using monoclonal antibodies to CD45, CD44 and CD133. The cytokine profiles of ascitic fluid and blood serum (IL-1β, IL-18, IL-4, IL-10 and VEGF) were assessed by ELISA. Stem-like cells were found in all samples. 5 cell populations were evaluated. The number of cells expressing both markers: CD44 + and CD133+, was the lowest. The highest, about 32%, was the number of CD44+ cells. The number of cells CD45-CD44+CD133- in ascites strongly positively correlated with the content of IL-10 in ascites, and the numbers of CD45-CD133+ and CD45-CD44-CD133+ - with the level of VEGF in blood serum. No correlations were found between the numbers of stem-like cells and the disease stage or the level of CA125 in blood. The combination of IL-4 and IL-10 in ascites had the greatest significance in predicting the disease stage. These results suggest a relationship between the levels of VEGF, IL-10, and cancer stem cells in the OC ascites. Stem-like cells in OC ascites are heterogeneous and are present even at an early stage of the disease. It seems promising to study cell populations and cytokine profile of ascites together, to assess the biomarker potential of their combination.

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GCSF As a Potential Molecular Target for Overall Survival of Hepatocellular Carcinoma

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210322124003 ◽

2021 ◽

Vol 24 ◽

Author(s):

Heng Cao ◽

Peng Guo ◽

Xiaohui Wu ◽

Jiankun Li ◽

Chenlong Ge ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Survival Analysis ◽

Molecular Mechanisms ◽

Malignant Tumors ◽

Basic Research ◽

Clinical Samples ◽

Tumor Diameter ◽

Overall Survival Analysis

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of digestive tract in the world. Therefore, it is important to carry out studies on the molecular mechanisms of early diagnosis and treatment of HCC to reduce mortality. Methods: Bioinformatic analysis was performed to explore the significant role of GCSF on the occurrence and development of neoplasm. Differently expressed genes (DEGs) were screened, and the significant hub genes related with GCSF were identified by the multiple algorithms of Cytoscape. Functional annotation for DEGs, pathological stage and overall survival analysis were implemented. In addition, the verification for the role of GCSF on HCC was made via the clinical samples. A total of 70 participates diagnosed as HCC were recruited from November 2014 to November 2019. The immunohistochemistry assay, qRT-PCR, receiver operating characteristic (ROC) curves, and overall survival analysis were carried out. Results: GCSF was related with the tumor size, and the expression of GCSF was up-regulated in hepatocellular carcinoma tissues. The enrichment results of GO and KEGG analysis were mainly enriched in “Inflammatory response”, “Protein binding”, “Metabolic pathways”, and “Proteasome”. The tumor diameter (P < 0.001), and survival time (P < 0.001) were significantly associated with expression of GCSF via the verification of clinical data. The univariate and multivariate Cox proportional regression analysis manifested that high expression of GCSF in patients with HCC was related to poor OS. Conclusion: The expression level of GCSF is significantly associated with the prognostic survival of HCC, and it is expected to become a new prognostic marker of HCC, providing a novel idea for future basic research as well as targeted therapy.

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Epidemiology of ovarian cancer in Kazakhstan (2013-2018)

Oncologia i radiologia Kazakhstana ◽

10.52532/2521-6414-2020-2-56-9-11 ◽

2020 ◽

Vol 56 (2) ◽

pp. 9-11

Author(s):

E. K. Kukubasov ◽

A. R. Satanova ◽

R. O. Bolatbekova ◽

D. B. Kaldibekov ◽

А. А. Kurmanova ◽

...

Keyword(s):

Ovarian Cancer ◽

Western Europe ◽

Malignant Tumors ◽

Age Groups ◽

Incidence Rates ◽

Preventative Measures ◽

Age Related ◽

Working Age ◽

East Kazakhstan ◽

The Republic

Relevance: According to Globocan 2018, ovarian cancer (OC) ranks 18th among all other cancers affecting women around the world. More than 295,414 new cases of OC were reported only in 2018. The incidence is low in Western Europe and is high in Latvia, Poland, Lithuania, Estonia, Russia, and Kazakhstan. In 2018, ovarian malignancies ranked 8th (3.1%) in Kazakhstan among all malignant tumors. At that, there are no clearly recognized preventative measures to ensure the early detection of OC. 70% of ovarian malignancies are detected at stage III-IV. The purpose of this study was to conduct a comparative analysis and assessment of the dynamics of the prevalence of OC in the Republic of Kazakhstan in 2013-2018. Results: The analysis of age-related OC incidence in Kazakhstan showed the presence of ovarian malignancies in all age groups, with a marked increase by the age of 65-69 years. The majority of patients were women of the working age. Differences were found in the incidence rates by regions of the country. In the study period, the incidence was high in Qostanai, Pavlodar, and North Kazakhstan regions (northern part of the country) and Almaty. The incidence was below the national average in Atyrau, Jambyl, and South Kazakhstan regions (southern and western parts of the country). Recent years have witnessed a sharp increase in OC incidence in East Kazakhstan and Karaganda regions. Conclusion: The analysis of OC prevalence in the Republic of Kazakhstan and by regions showed an increase in OC incidence. There is a marked increase in OC detection in the northern areas of the country and a decrease in the number of cases in the south.

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Treatment-Resistant Hypercalcemia Secondary to Ectopic PTH Hypersecretion From Disseminated Ovarian Cancer

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.464 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A228-A229

Author(s):

Alexander M Balinski ◽

Neil J Khatter ◽

Jeffrey M Gold ◽

Krishna S Pothugunta ◽

Vamshi K Garlapaty ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Detection ◽

Serum Calcium ◽

Poor Prognosis ◽

Malignant Tumors ◽

Ovarian Adenocarcinoma ◽

Hypercalcemia Of Malignancy ◽

Organ System Failure ◽

Sestamibi Scan ◽

Total Body

Abstract Background: Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH from a disseminated mucinous ovarian adenocarcinoma. Case Presentation: A 45-year-old female presented with confusion, constipation, fatigue, and abdominal pain two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with metastasis to the bladder, parametrium, vagina, right ovary, and rectosigmoid. Subsequent CT revealed numerous bilateral pulmonary nodules, hilar adenopathy, liver lesions, and abdominal adenopathy. On exam, she was tachycardic and hypertensive with diaphoresis, dry mucous membranes, respiratory distress, guarded abdominal tenderness, and altered mental status. Her labs were significant for a serum calcium of 21.7 mg/dL, creatinine of 1.93 mg/dL, ferritin of 2,379 ng/mL, leukocytosis of 21.9 bil/L, PTH of 1,061 pg/mL, and PTHrP of 29 pmol/L. Ectopic PTH secretion was highly suspected after negative parathyroid ultrasound. Pamidronate (60 mg IV), calcitonin (200 U IM), and fluid resuscitation were unable to normalize her serum calcium, resulting in the need for dialysis and subsequent continuous renal replacement therapy. Further intervention with denosumab (120 mg SQ), etelcalcetide (5 mg IV), and cinacalcet (60 mg PO) was also attempted. Serum calcium began to decline, but repeat PTH resulted greater than 2,500 pg/mL. Unfortunately, the patient died just one week into her hospital course from septic shock and multi-organ system failure. Discussion: Hypercalcemia of malignancy typically arises from tumor secretion of PTHrP, cytokine release from osteolytic metastases, or tumor production of calcitriol. In cases of hypercalcemia due to excess PTH secretion, primary parathyroid etiologies are typically considered while ectopic PTH-secreting tumors are rare. PTH staining of biopsy specimens and total body sestamibi scan may prove useful in the early detection and treatment of these tumors, but HCM offers a poor prognosis with mean survival of 2 to 3 months and in-hospital mortality of 6.8%. Currently, there are only three cases in the reported literature of ectopic PTH-induced hypercalcemia related to ovarian cancer. To our knowledge, this is the fourth reported case. Conclusion: Ectopic PTH-secreting tumors carry a poor prognosis and should be considered in cancer patients presenting with PTH-associated hypercalcemia. Biopsy staining for PTH and total body sestamibi scan may assist in the early detection of these tumors, but current treatment strategies offer suboptimal outcomes.

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mRNAsi Index-based Integrative Analysis for the Identification of New Prognostic Models for Ovarian Cancer

10.21203/rs.3.rs-76966/v1 ◽

2020 ◽

Author(s):

Xue Pan ◽

Xiaoxin Ma

Keyword(s):

Ovarian Cancer ◽

Clinical Characteristics ◽

Malignant Tumors ◽

Lymphatic Invasion ◽

Prognostic Models ◽

Overall Survival Rate ◽

Female Reproductive System ◽

Competing Endogenous Rna ◽

Competing Endogenous Rna Network ◽

Grade 3

Abstract Ovarian cancer (OC) has the highest mortality rate among all female reproductive system malignant tumors worldwide. In this study, we aimed to investigate OC from several perspectives by using machine learning. Our results showed that the mRNA expression-stemness index (mRNAsi) is closely related to clinical characteristics of OC patients, as OC patients with venous or lymphatic invasion had higher mRNAsi score compared to patients with no invasion. Furhter grade 3/4 patient group had higher mRNAsi scores compared to the grade1/2 group. We also found that mRNAsi is closely related to immune infiltration in OC. We also built a competing endogenous RNA network, which contained 4 miRNAs, 5 lncRNAs, and 1 mRNA, by using Cytoscape based on the differentially expressed genes of the high- and low-mRNAsi groups. Through Lassio regression, we also established a model including 7 lncRNAs and 2miRNAs, which could effectively categorize OC patients into two groups based on the median risk score. We then developed a nomogram model which could effectively forecast the overall survival rate of OC for 1-, 3-, and 5-year period. The models assessed in this study showed potential for clinical application in treatment decisions for OC.

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