Tumor Marker For Ovarian Cancer Research Articles

The pivotal role of long non-coding RNAs as potential biomarkers and modulators of chemoresistance in ovarian cancer (OC).

Ovarian cancer (OC) is a fatal gynecological disease that is often diagnosed at later stages due to its asymptomatic nature and the absence of efficient early-stage biomarkers. Previous studies have identified genes with abnormal expression in OC that couldn't be explained by methylation or mutation, indicating alternative mechanisms of gene regulation. Recent advances in human transcriptome studies have led to research on non-coding RNAs (ncRNAs) as regulators of cancer gene expression. Long non-coding RNAs (lncRNAs), a class of ncRNAs with a length greater than 200 nucleotides, have been identified as crucial regulators of physiological processes and human diseases, including cancer. Dysregulated lncRNA expression has also been found to play a crucial role in ovarian carcinogenesis, indicating their potential as novel and non-invasive biomarkers for improving OC management. However, despite the discovery of several thousand lncRNAs, only one has been approved for clinical use as a biomarker in cancer, highlighting the importance of further research in this field. In addition to their potential as biomarkers, lncRNAs have been implicated in modulating chemoresistance, a major problem in OC. Several studies have identified altered lncRNA expression upon drug treatment, further emphasizing their potential to modulate chemoresistance. In this review, we highlight the characteristics of lncRNAs, their function, and their potential to serve as tumor markers in OC. We also discuss a few databases providing detailed information on lncRNAs in various cancer types. Despite the promising potential of lncRNAs, further research is necessary to fully understand their role in cancer and develop effective strategies to combat this devastating disease.

D-dimer, Fibrinogen and Tumor Marker Levels in Patients with benign and Malignant Ovarian Tumors.

Limited studies have investigated the differences between the levels of plasma coagulants and tumor markers in ovarian cancer. Therefore, we conducted this study to determine and compare the level of coagulation, fibrinolysis and tumor markers in patients with benign and malignant ovarian tumors. This cross-sectional study was conducted between January 2022 and February 2023 in Imam Hossein Hospital on patients with ovarian mass. Laboratory tests included platelet count, PT, INR, PTT, fibrinogen and D-dimer were sent to the pathology laboratory to be examined by a pathologist. Based on histopathology, patients were divided into benign, borderline and malignant groups. Logistic regression was used for determine predictors of malignancy. Receiver operating characteristics (ROC) curves and their corresponding 95% CI were determined for the predictor value of the full model. From 141 investigated patients, tumor type in 124 (87.94%) patients were benign, in 12 (8.51%) was malignant and in 5 (3.55%) was borderline. D-dimer, Ca-125 and HE4 were significantly higher in the patients with malignant tumor type (P<0.001), whereas AFP was significantly higher in patients with borderline tumor type (P<0.001). With one-unit increase in D-dimer odds of borderline/malignant tumor 0.3% increases (OR=1.003, 95% CI: 1.001, 1.006) and with one-unit increase in Ca-125 odds of borderline/malignant tumor 1% increases (OR=1.01, 95% CI: 1.003, 1.02). We found that plasma fibrinogen, D-dimer and Ca-125 levels are independently associated with malignant ovarian tumors and combined use of these markers has the high discriminant power for distinction of benign and malignant ovarian masses.<br />.

Tetrahedral DNA nanostructure enhanced toehold-mediated strand displacement for highly sensitive electrochemiluminescence assay of CA125

Cancer antigen 125 (CA125) is a typical tumor marker of ovarian cancer. Here, a multi-amplified electrochemiluminescence (ECL) aptasensor was developed for efficient recognition of CA125 using tetrahedral DNA nanostructure (TDN) enhanced toehold-mediated strand displacement (TMSD) coupled with gold nanoparticles/Ru(bpy)32+/metal–organic framework (AuNPs/Ru/ZIF-MOF) signal probe. AuNPs and Ru(bpy)32+ modified ZIF-MOF acted as initial ECL signal and further used for the immobilization of TDN, the activated DNA templates on the surface of TDN were firstly hybridized with ferrocene labeled DNA probe (S6) and S5, in which, S6 acted as the energy acceptor of ECL signal from Ru(bpy)32+, making the sensor in a “signal-off” state. After the specific recognition of aptamer (AP) with CA125, DNA initiator (S7) was freed to induce the happen of TMSD by using S8 as the helper DNA, accompanying with the release of S6 from the electrode surface and the recovery of Ru(bpy)32+ ECL signal, making the sensor in a “signal-on” state. Then, S7 was recycled for the next TMSD, making the sensor highly sensitive with a detection limit of 6 × 10-3 pg/mL. Moreover, the proposed aptasensor achieved high performance for CA125 detection in human serum samples, illustrating the reliability of the sensor in clinical analysis.

(032) A Large Retroperitoneal Schwannoma Masquerading as Genito-Urinary Syndrome of Menopause

Abstract Introduction Retroperitoneal schwannomas are extremely rare, slow growing, benign, neurogenic tumors. Their diagnosis is challenging and often incidentally found upon evaluation of vague symptoms. Extrinsic compression to nearby organs or nerves may cause pain and paresthesia. Vulvar pain as a presenting symptom of a retroperitoneal schwannoma is reported in the literature in a case with pudendal nerve involvement. Here we present a case report of a patient who presented with vulvar burning and lower urinary tract irritative symptoms which was found to have a large infra-hepatic retroperitoneal schwannoma. Objectives In this report we show case how performing a detailed neurological evaluation and having a good understanding of the vulvar, perineal, and lower extremity dermatomal innervation have assisted in early diagnosis and treatment of a large retroperitoneal schwannoma. Methods A 65-year-old menopausal woman presented to her primary provider for a 3-month-history of worsening vulvar burning sensation associated with urinary burning, frequency, and nocturia. The pain is worse at night and when sitting for more than an hour. The patient endorsed low back pain that radiated like pins down her anterior thighs. The patient underwent evaluation by her referring provider to rule out a urinary tract infections and vaginitis. She was treated with vaginal estrogen tablets with partial relief for a working diagnosis of Urogenital Syndrome of Menopause. Patient was then referred to Gynecology due to inadequate relief. A detailed pelvic examination revealed normal labia majora and minora with no erythema or swelling. The Vestibule, Bartholin and Skene glands were non tender. Q-tip testing provoked burning sensation in the left and right labia minora on the medial and lateral aspect as well as the labia majora. Pelvic Floor evaluation elicited left pelvic floor tenderness and bilateral ischial spine pain concerning for Pudendal neuralgia. Also, noted paresthesia overlying the left lower extremity at the L3 and L4 distribution at the medial thigh (Figure-1) The patient underwent a bilateral pudendal block with total resolution of her vulvar pain for 24 hours and hence, lumbar and pelvic nerve entrapment was suspected. Magnetic Resonance Imaging was requested. Evaluation revealed a 3.3x4.4cm left ovarian mass and uterine fibroids that could potentially explain L2-L5 radiculopathy. The Lumbar MRI noted a cystic mass in the right mid abdomen for which further evaluation with CT scan was recommended. (Image-1). Referral to Surgical Oncology and Gyn oncology was sought. Epithelial ovarian cancer tumor markers were normal. Catecholamine studies were nonrevealing except for unexplained increase in dopamine levels. Results Surgical excision of the retroperitoneal and ovarian tumor revealed a left ovarian Fibroma and Schwannoma with Cystic Degeneration, confirmed with Immuno-peroxidase studies for S100 and SOX10. The patient had an uncomplicated post-operative course and remains asymptomatic with total resolution of her urinary and vulvar burning symptoms. Conclusions This a case report of vulvar and urethral paresthesia caused by an exceedingly rare tumor located high in the retroperitoneum. Diagnosis was aided by detailed history, comprehensive gynecological, and neurodermatomal evaluation. Appropriate imaging and timely referral led to early diagnosis and treatment, resulting in symptom resolution. Disclosure No.

Evaluation of He4 Use in the Diagnosis of Ovarian Cancer: First and Second Recurrence, and an Analysis of HE4 Concentration during Second- and Third-Line Chemotherapy.

HE4 is a commonly used tumor marker for ovarian cancer (OC) diagnosis. In our study, we aimed to assess its use in the diagnosis of subsequent OC recurrences and to evaluate its changes during recurrence diagnosis and the subsequent lines of chemotherapy treatment. This retrospective single center study was conducted on 188 patients treated for ovarian cancer recurrence at the Department of Gynecological Surgery and Gynecological Oncology. The sensitivity and specificity of HE4 for patient survival prediction were analyzed using Receiver Operating Characteristics (ROC) and area under the curve (AUC) with 95% confidence intervals (95% CI). Survival times to reach one of the endpoints (OS, PFS, TFI, PFS2, TFI2) were analyzed using Kaplan-Meier curves. Elevated HE4 levels at the time of first relapse diagnosis, and after the third and the last course of second-line chemotherapy, significantly influences the time from OC diagnosis until first disease recurrence (PFS2) (p = 0.005, p = 0.015 and p = 0.002, respectively). Additionally, elevated serum HE4 concentration at the time of OC diagnosis (p = 0.012), and its later recurrence (first (p < 0.001), and second recurrent diagnosis (p = 0.143)) significantly influences patient OS. Increased HE4 concentration at the end of chemotherapeutic treatment negatively affects overall patient survival ((p = 0.006 for second line chemotherapy and (p = 0.022) for elevated HE4 concentration after the last course of third-line chemotherapy). Our preliminary results show an encouraging diagnostic and prognostic role of HE4 in recurrent ovarian cancer. HE4 measurements at different treatment time points during the second- and third-line chemotherapy treatment seem to correlate with patient survival.

A novel carbohydrate antigen 125 electrochemical sensor based on sweet almond oil organo-hydrogels

Ovarian cancer is a gynecological disease causing many deaths among women around the world. Carbohydrate antigen 125 (CA-125) is a single biomarker known to be a tumor marker of ovarian cancer. CA-125 is widely used to monitor the treatment process, recurrences, and for the detection of ovarian cancer. Herein, organo-hydrogels were prepared in order to detect CA-125 sensitively in serum medium with electrochemical methods. Organo-hydrogels were obtained by the free radical polymerization reaction using agar and glycerol with varying proportions of sweet almond oil using methylene bisacrylamide (MBA) or glutaraldehyde (GA) crosslinkers. Electrochemical measurements were performed with cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV) on organo-hydrogel sweet almond oil (OHSAO) prepared in the presence and absence of CA-125. As a result of these measurements, two distinct linear ranges of 1–50 ng/mL and 100–1000 ng/mL were obtained. In addition, LOD and LOQ values for the sensor were calculated as 0.41 μU/mL and 1.24 μU/mL, respectively. In conclusion, the OHSAO-based electrochemical sensor is a promising electrode for CA-125 detection.

Defying expectations: follicular carcinoma thyroid with lung metastasis and elevated CA 125: images

Background: Follicular thyroid carcinoma (FTC) is a type of thyroid cancer that arises from the follicular cells of the thyroid gland. It accounts for about 10%-15% of all thyroid cancers. CA 125 is a protein that is often used as a tumor marker for ovarian cancer, but it can also be elevated in other types of cancers, including thyroid cancer. The significance of raised CA 125 levels in FTC is not clear, but it indicates a more advanced or aggressive form of the disease [1,2]. Case Presentation: A 62-year-old male presented with a painless neck mass (Figure 1) for 8 years. Ultrasonography revealed a solid nodule in the left lobe of the thyroid gland. Fine-needle aspiration cytology of the nodule showed features of follicular neoplasm. Contrast-enhanced computed tomography (CECT) abdomen and blood routine ruled out other causes of raised CA 125. Chest X ray and CECT neck (Figure 2) and thorax showed lung (Figure 3) and thoracic vertebra metastasis (Figure 5). Total thyroidectomy with bilateral central compartment lymph node dissection was performed. Histopathology confirmed FTC (Figure 4) with capsular invasion, and lymphovascular and perineural invasion and lymph node-positive. The tumor was classified as T3bN1a according to the tumor, nodes, and metastasis staging system. I131 scan post-surgery showed uptake in lung metastasis sites which confirmed the diagnosis. Conclusion: The role of serum tumor markers, such as CA 125, in predicting the prognosis of FTC is not well established. However, elevated CA 125 levels have been reported in some cases of thyroid carcinoma with metastasis, and may reflect the presence of peritoneal or pleural involvement [3,4]. This case highlights the aggressive nature of FTC with metastasis and the limited treatment options available for patients with advanced disease. CA 125 as a prognostic marker in FTC warrants further investigation [5].

Nectin-4 as Blood-Based Biomarker Enables Detection of Early Ovarian Cancer Stages.

Ovarian cancer is the third most common gynecological malignancy and has the highest mortality rate. Owing to unspecific symptoms, ovarian cancer is not detected until an advanced stage in about two-thirds of cases. Therefore, it is crucial to establish reliable biomarkers for the early stages to improve the patients’ prognosis. The aim of this study is to investigate whether the ADAM17 substrates Nectin-4, Heparin-binding EGF-like growth factor (HB-EGF) and Amphiregulin (AREG) could function as potential tumor markers for ovarian cancer. In this study a set of 231 sera consisting of 131 ovarian cancer patients and 100 healthy age-matched controls were assembled. Nectin-4, HB-EGF and AREG levels of preoperatively collected sera were determined by enzyme-linked immunosorbent assay (ELISA). Our analysis revealed that Nectin-4 and HB-EGF were significantly increased compared to the age-matched control group (p < 0.0001, p = 0.016). Strikingly, significantly higher Nectin-4 and HB-EGF levels were detected in early-stage FIGO I/II (p <0.001; p = 0.025) compared to healthy controls. Eighty-four percent (16/19) of patients with low Ca-125 levels showed increased Nectin-4 levels. Our study proposes Nectin-4 and HB-EGF as promising blood-based biomarkers for the detection of early stages of ovarian cancer patients that would not have been detected by Ca-125.

TRANSCRIPTOMIC DIFFERENCES IN MONOZYGOTIC TWINS WITH OVARIAN CANCER

Objectives: The most significant barrier to treating epithelial ovarian cancer(EOC), is the late diagnosis and the emergence of chemotherapy resistance in the early stages.The ineffectiveness of standard treatment protocols in advanced-stage cases highlights the value of individualized EOC treatment.Even monozygotic(MZ) twins, with almost the same genotype in nature, can develop different phenotypic characteristics throughout life. Materials-Methods: In this context, the peripheral blood and ovarian tissues of monozygotic twins who are discordant in terms of ovarian cancer and the other healthy sibling who is a BRCA1 mutation carrier were compared in the study to analyze all RNA molecules transcribed at the genome level using next-generation sequencing technology.Through analyzing the molecules transcribed in the whole genome,the genetic variations underlying the development of ovarian cancer in a high-risk family bearing the BRCA1 mutation but only one of whom was found to have ovarian cancer were examined. Results: As a result of the transcriptomic analysis of the total RNA of 6 samples obtained from the ovarian tissues and peripheral blood samples of MZ twins with ovarian cancer and healthy sibling, the protein-encoding protein that shows expression changes in tissue and blood compared to healthy people genes,lncRNAs,precursor-miRNAs and fusion-transcripts have been identified.Filtering procedures and expression change coefficients(log2Fc) were calculated based on the expression data of identified ovarian cancer tumor markers CA125 and CA15-3. Conclusions: According to our study the expression levels of 66 protein-coding genes,23 novel lncRNAs,9 miRNAs and,2 fusion transcripts were found to vary in three groups and,these molecules are thought to be candidate molecules associated with epithelial ovarian cancer.

Osteopontin as a Tumor Marker in Ovarian Cancer.

Ovarian cancer is associated with high morbidity and mortality. This is due to the nonspecific symptoms and no effective screening methods. Currently, carbohydrate antigen-125 (CA125) is used as a tumor biomarker for the diagnosis of ovarian cancer, but it has its own limitations. Hence, there is a need for other tumor biomarkers for the diagnosis of ovarian cancer. Objective of the study was to evaluate the diagnostic test characteristics of plasma osteopontin (OPN) in detecting ovarian malignancy and comparing its performance with CA125. This is a prospective cross-sectional diagnostic test evaluation. Women with adnexal mass detected by clinical or radiological examination were enrolled as suspected cases. Women who presented with other gynecological conditions were enrolled as controls. OPN and CA125 levels were measured in all enrolled subjects. Among 106 women enrolled, 26 were ovarian cancer, 31 had benign ovarian masses, and 49 were controls. Median plasma CA125 levels were higher in subjects with ovarian cancer (298 U/ml; interquartile range [IQR]: 84-1082 U/ml vs. 37.5U/ml; IQR: 17.6-82.9U/ml; P < 0.001). CA125 sensitivity, specificity, positive, and negative likelihood ratios were 88.5%, 61.3%, 2.10, and 0.19, respectively. Median plasma OPN levels were higher in subjects with ovarian cancer (63.1 ng/ml; IQR: 39.3-137 ng/ml vs. 27 ng/ml; IQR: 20-52 ng/ml; P = 0.001). Sensitivity, specificity, positive, and negative likelihood ratios of OPN were 50%, 87%, 2.58, and 0.62, respectively. OPN levels were higher in ovarian cancer than in the benign ovarian mass and had better specificity than CA125. OPN can better differentiate between benign and malignant ovarian mass as compared to CA125.

Biomarker-based early detection of epithelial ovarian cancer based on a five-protein signature in patient\u2019s plasma \u2013 a prospective trial

BackgroundTrial on five plasma biomarkers (CA125, HE4, OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors.MethodsIn this unicentric prospective trial preoperative blood samples of 43 women with ovarian masses determined for ovarian surgery were analyzed. 25 patients had pathologically confirmed benign, 18 malignant ovarian tumors. Blood plasma was analyzed for CA125, HE4, OPN, leptin, prolactin and MIF by multiplex immunoassay analysis. Each single protein and a logistical regression model including all the listed proteins were tested as preoperative predictive marker for suspect ovarian masses.ResultsPlasma CA125 was confirmed as a highly accurate tumor marker in ovarian cancer. HE4, OPN, leptin and prolactin plasma levels differed significantly between benign and malignant ovarian masses. With a logistical regression model a formula including CA125, HE4, OPN, leptin and prolactin was developed to predict malignant ovarian tumors. With a discriminatory AUC of 0.96 it showed to be a highly sensitive and specific diagnostic test for a malignant ovarian tumor.ConclusionsThe calculated formula with the combination of CA125, HE4, OPN, leptin and prolactin plasma levels surpasses each single marker in its diagnostic value to discriminate between benign and malignant ovarian tumors. The formula, applied to our patient population was highly accurate but should be validated in a larger cohort.Trial registrationClinical Trials.gov under NCT01763125, registered Jan. 8, 2013.

Enrichment and Detection Method for the Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-analysis

(Abstracted from Gynecol Oncol 2021;161:613–620) In part due to a lack of early symptoms and robust screening strategies, ovarian cancer is often diagnosed in later stages and has the highest worldwide mortality among gynecologic malignancies. Tumor markers CA125 and HE4 are effective in the diagnosis of ovarian cancer; however, there is a need for prognostic tumor markers for ovarian cancer.

Cancer antigen-125 is a predictor of mortality in patients with pulmonary arterial hypertension

BackgroundCarbohydrate antigen 125 (CA 125), known as a tumor marker for ovarian cancer, has been reported to increase and be associated with severity in heart failure and chronic obstructive pulmonary disease. Patients with pulmonary arterial hypertension may also die due to developing right heart failure. The aim of this study is to evaluate the prognostic role of CA-125 in PAH patients. MethodsA total of 40 consecutive patients with PAH were evaluated prospectively. The mean age of patients was 52 ± 11 years (12% males, 88% females) with a median follow-up period of 16 months. ResultsAfter follow-up period, 12 out of 40 patients (30%) died. CA-125 levels were higher among those who died compared to those who survived [78.5 (11.0–292) vs. 27.5 (2.10–138) U/ml, p = 0.001]. The optimal cut-off value of CA-125 to predict mortality was found as 35.29 U/ml, with 85.7% specificity and 75% sensitivity. In multivariable Cox proportional-hazards model with forward stepwise method; CA-125 > 35.32 U/ml on admission (HR = 7.645, 95% CI: 1.356–43.121, p = 0.021), age (HR = 1.132, 95% CI: 1.040–1.233, p = 0.004), TAPSE (HR = 0.740, 95% CI: 0.549–0.998, p = 0.048) and uric acid (HR = 1.444, 95% CI: 1.022–2.042, p = 0.037) remained associated with an increased risk of death. ConclusionIn this study, we showed for the first time that serum CA-125 values were an independent predictor for the long-term mortality in PAH patients.

Immunohistochemical Study of CA 125 in Surface Epithelial Tumors of Ovary in Correlation with Serum Levels

Background:&#x0D; Ovarian carcinoma is the 4th leading cancer among women in India. Primary ovarian neoplasms exhibit a wide range of histopathological patterns and tumors with epithelial differentiation are most frequent. Among malignant tumors, most common histological type is serous adenocarcinoma whose diagnosis is established in advanced stages of disease in approximately 75% of patients.&#x0D; The most widely used tumor marker in ovarian cancer, often considered “gold standard” is Cancer Antigen125. Cancer Antigen 125 is a high molecular weight glycoprotein which is raised in approximately 90% of patients with advanced epithelial ovarian cancer.&#x0D; &#x0D; Methods:&#x0D; A 2 year prospective study included 81 cases of ovarian neoplasms with surface epithelial differentiation. The specimens were fixed in 10% formalin, routinely processed. Sections of 4-5 microns thickness were obtained from the paraffin block and stained with Hematoxylin &amp; Eosin. The tumors were categorised according to WHO classification. Immunohistochemical analysis of Cancer Antigen 125 was done in all malignant &amp; borderline tumors.&#x0D; &#x0D; Result:&#x0D; A total of 81 cases were studied. There were 15 cases with elevated serum Cancer Antigen 125 levels. Of these 8 showed positive tissue expression. The sensitivity of serum Cancer Antigen 125 was 68.75% &amp; its specificity was 93.8%.&#x0D; &#x0D; Conclusion: &#x0D; Serum Cancer Antigen 125 is elevated in ovarian tumors especially in malignant surface epithelial tumors &amp; more commonly in serous cystadenocarcinoma. There was a good correlation between serum levels &amp; tissue expression of Cancer Antigen 125.

Cancer Antigen 125 Serum Level in Head and Neck Diffuse Large B-Cell Lymphoma

Background : Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of the Non-Hodgkin Lymphoma (LNH). Until now, lactate dehydrogenase (LDH) is the only tumor marker to assess DLBCL progression; however, increased LDH is a relatively non-specific biomarker. Cancer antigen 125 (CA-125) serum level have been used as a tumor marker in ovarian cancer. The aim of this study was to explore the possible role of CA-125 serum level as a tumor marker in head and neck DLBCL. Methods : This was an observational descriptive study among consecutively sampled DLBCL patients. CA-125 serum level examination was carried out (ADVIA Centaur CA-125II) and described along with the clinical characteristics of DLBCL patients. Results : DLBCL was mostly observed in males (54.05%), most often in the 55-65 year age group (51.3%), with stage 1 DLBCL was the most prevalent (71.9%). The mean CA-125 serum level was 22.9 U/ml and increased in patients with advanced DLBCL. Conclusions : Increased CA-125 serum level in DLBCL, especially at advanced stages, suggests that CA-125 serum level may be of benefit as a tumor marker in the head and neck DLBCL. Further study is in need to explore the role of CA-125. 1. Kementerian Kesehatan Republik Indonesia. Data dan kondisi penyakit limfoma di Indonesia. InfoDatin Pusat Data dan Informasi Kementerian Kesehatan RI. 2015 [cited 2020 March 18] Available from: https://www.kemkes.go.id/resources/download/pusdatin/infodatin/infodatin-limfoma.pdf 2. Dwianingsih EK, Indrawati, Hardianti MS, Malueka RG , Iswar RR, Sutapa S, et al. Histopathological features of lymphoma in Yogyakarta, Indonesia. Asian Pac J Cancer Prev. 2016;17(9):4213–16. 3. Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan RI. Riset Kesehatan Dasar (RISKESDAS) 2013. Jakarta: Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan RI; 2013 4. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32(27):3059–67. 5. Ziepert M, Hasenclever D, Kuhnt E, Glass B, Schmitz N, Pfreundschuh, et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(14):2373-2380. 6. Gutiérrez A, Martínez-Serra J, Barceló B, Sampol A, Vinas L, Gonzales G, et al. Prognostic value of serum CA125 levels in diffuse large B-cell lymphoma: potential role of a new sex and age adjusted reference value. Int J Lab Hematol. 2010; 32(6 Pt 2): 582–9. 7. Dilek I, Ayakta H, Demir C, Meral C, Ozturk M. CA 125 levels in patients with Non-Hodgkin lymphoma and other hematologic malignancies. Clin Lab Haematol. 2005;27(1):51–5. 8. Memar B, Aledavood A, Shahidsales S, Ahadi M, Farzadnia, Raziee HR, et al. The prognostic role of tumor marker CA-125 in B-Cell non-Hodgkin’s Lymphoma. Iran J Cancer Prev. 2015;8(1):42–6. 9. Garg S, Goyal B. Evaluation of CA-125 as a prognostic marker in patients with Non-Hodgkin’s lymphoma. International Journal of Medical and Health Research. 2017;3(4):13–5. 10. Paoli CJ, Bach BA, Quach D, Tsai KT, Wong B, Kallich J. Performance status of real-world oncology patients before and after first course of chemotherapy. The Journal of Community and Supportive Oncology. 2014; 12(5):163–70. 11. Yadav C, Ahmad A, D’Souza B, Agarwal A, Nandini M, Prabhu KA, et al. Serum lactate dehydrogenase in Non-Hodgkin’s lymphoma: a prognostic indicator. Indian J Clin Biochem. 2016;31(2):240–2.

The expression levels and clinical significance of MFG-E8 and CD133 in epithelial ovarian cancer

The aim of our study was to test whether there is an association between high expression of milk fat globule EGF factor 8 (MFG-E8) and CD133 presence or clinical outcomes of patients with epithelial ovarian cancer (EOC). MFG-E8 and CD133 expression levels were analyzed by immunohistochemistry in 88 EOC tumor specimens. High expression of MFG-E8 directly and significantly correlated with the presence of CD133 immunostaining (R = 0.353, p=.001), whereas immunostaining of MFG-E8 and CD133 significantly correlated with FIGO stage, tumor grade, debulking status, the dualistic model, ascites status, and nonresponse to chemotherapy (p<.05). It was also found that high expression of MFG-E8 and CD133 presence is a potent predictor of poor clinical outcomes among patients with EOC. Our study is the first to show that high expression of MFG-E8 in EOCs positively correlates with CD133 presence. Further research on MFG-E8 in EOC is needed to determine whether MFG-E8 is a new tumor marker of ovarian cancer and a new target for anticancer therapy as well as whether it can interact with cancer stem cell inhibitors for the treatment of refractory tumors.

Assessment of the diagnostic value of using serum CA125 and GI-RADS system in the evaluation of adnexal masses.

Cancer antigen 125 (CA125) is a valuable tumor marker for ovarian cancer. Gynecology Imaging Reporting and Data System (GI-RADS) is proved to be effective at identifying the adnexal masses. We investigated whether the combination of these two methods can improve the diagnostic accuracy of ovarian cancer.We retrospectively analyzed preoperative data of 325 patients diagnosed with suspected adnexal mass, 196 patients with benign ovarian masses and 129 with malignant ovarian cancer (stage I: 34, II: 16, III: 61, IV: 18). CA125 was analyzed using the ARCHITECT system, GI-RADS was evaluated according to the International Ovarian Tumor Analysis consensus nomenclature and definitions. Sensitivities and specificities were also calculated for GI-RADS, CA125 and the combinations.The sensitivity, specificity and accuracy of CA125, GI-RADS were 75.97%, 79.59%, 78.15%, and 90.70%, 90.82%,90.77%, the combination data were 94.79%, 96.00%,95.53%. The AUC of combined diagnostic methods was the largest and significantly better compared with each method alone, P < .001). For stage I-II malignancy, GI-RADS as a single method was superior to CA125.Combined use of serum CA 125 and GI-RADS system improved the identification of adnexal masses at high risk of malignancy and could be used for clinical decision-making.

Circulating non-coding RNAs in recurrent and metastatic ovarian cancer.

Ovarian cancer has a poor outcome because it is usually detected at advanced tumor stages, and the majority of the patients develop disease relapse as a result of chemotherapy resistance. This most lethal gynecological malignancy metastasizes within the peritoneal fluid or ascites to pelvic and distal organs. In ovarian cancer progression and metastasis, small non-coding RNAs (ncRNAs), including long noncoding RNAs and microRNAs have been recognized as important regulators. Their dysregulation modulates gene expression and cellular signal pathways and can be detected in liquid biopsies. In this review, we provide an overview on circulating plasma and serum ncRNAs participating in tumor cell migration and invasion, and contributing to recurrence and metastasis of ovarian cancer. We will also discuss the development of potential, novel therapies using ncRNAs as target molecules or tumor markers for ovarian cancer.

Usefulness of HE4 protein in differentiation of pelvic masses in woman.

IntroductionHE4 protein (human epididymis protein-4), which is the fourth subfraction of human epithelial protein, is a glycoprotein widely used as a tumor marker in ovarian cancer. If was first discovered in the epididymal epithelium and recognized as a protease inhibitor contributing to sperm maturation. The plasma HE4 concentration may also be increased in gynecological pathologies other than ovarian cancer.Material and methodsThe study was conducted between 2016 and 2017 among patients hospitalized in the Academic Department of Gynaecology. A total of 191 women were examined. Depending on the type of pathology which was the reason for hospitalization, 4 groups of patients were identified in the study. The first of these included 30 patients with ovarian cancer, the second 33 patients with benign ovarian lesion, the third 50 patients with endometrial cancer, and the fourth 28 patients with leiomyomas.ResultsThe highest concentration of HE4 protein was found in women with ovarian cancer, and it was statistically significantly higher compared to all other groups. Lower HE4 protein concentration than in women with ovarian cancer was reported in women with endometrial cancer, but it was statistically significantly higher compared to patients with uterine fibroids.ConclusionsThis marker may have significant clinical value in the differentiation of benign ovarian pathology from ovarian cancer. The study confirms the validity of using HE4 results in the assessment of potential malignancy of ovarian and endometrial lesions.

Evaluation of Serum HE4 in Ovarian Tumors, Its Comparison with Serum CA125 and Correlation with Histological Subtypes

Ovarian cancer is the seventh most common cancer in women and second most common female genital cancer in India. The high mortality is due to the fact that ovarian cancer is detected in later stages because of its non-specific symptoms like bloating, pain and increased size, gastrointestinal symptoms like indigestion, constipation or nausea with pelvic symptoms like bleeding. Cancer antigen 125 (CA125) has been useful for detection of ovarian cancer and also for follow-up. Recently, another tumor marker for ovarian cancer has been proposed, the Human Epididymis 4 protein (HE4), frequently over-expressed in ovarian cancers, especially in serous and endometrioid histology. Descriptive study on 64 patients was done over a period of 1 year using pre- and postoperative serum samples for CA125 and HE4 and comparing them with histological diagnosis. ELISA for HE4 (Quantikine® Human HE4/WFDC2 Immunoassay) and chemiluminescence (ARCHITECT CA125 II assay) were used to assess CA125 levels and in serum. Results were compared between the two tumor markers, and statistical analysis (SPSS package Windows version 15.0) was done to compare the results. CA125 and HE4 levels were increased in malignant cases more than in benign cases. HE4 was seen as more specific than CA125, but, however, it did not prove superior in sensitivity. Hence, we conclude that CA125 along with HE4 will prove both as sensitive and as specific markers and hence prevent benign lesions being over-diagnosed and operated unnecessarily.