Predictor For Ovarian Cancer Research Articles

Comparison of CA-125 and HE4 in ovarian cancer recurrence detection

Purpose: This study aims to comprehensively evaluate CA-125 and HE4 as predictors of ovarian cancer (OC) recurrence in the same patient population. Methods: We systematically searched the WOS, PubMed, and Scopus databases on May 8, 2024, for studies investigating both tumor markers CA-125 and HE4 in the same patient population of ovarian cancer recurrence. We calculated pooled values of AUC, sensitivity, specificity, and univariate or multivariate hazard ratios (HR) for both tumor markers in serum using a random effects model and StataMP 17.0 software. Results: Thirteen articles comprising 1026 patients satisfied the inclusion criteria. Liquid-biopsy-based HE4 and CA-125 measurements were both proven to have high predictive value for detecting OC recurrence with comparable AUC values (AUCHE4:0.78, 95% CI=0.73-0.83; AUCCA125:0.80, 95% CI=0.73-0.88). While sensitivity of HE4 tests was higher than their specificity (SensitivityHE4=80.7%; 95% CI=73-88.4; I²=77.05%; p

Involvement of Protease-Activated Receptor2 Pleckstrin Homology Binding Domain in Ovarian Cancer: Expression in Fallopian Tubes and Drug Design.

Studying primordial events in cancer is pivotal for identifying predictive molecular indicators and for targeted intervention. While the involvement of G-protein-coupled receptors (GPCRs) in cancer is growing, GPCR-based therapies are yet rare. Here, we demonstrate the overexpression of protease-activated receptor 2 (PAR2), a GPCR member in the fallopian tubes (FTs) of high-risk BRCA carriers as compared to null in healthy tissues of FT. FTs, the origin of ovarian cancer, are known to express genes of serous tubal intraepithelial carcinoma (STICs), a precursor lesion of high-grade serous carcinoma (HGSC). PAR2 expression in FTs may serve as an early prediction sensor for ovarian cancer. We show now that knocking down Par2 inhibits ovarian cancer peritoneal dissemination in vivo, pointing to the central role of PAR2. Previously we identified pleckstrin homology (PH) binding domains within PAR1,2&4 as critical sites for cancer-growth. These motifs associate with PH-signal proteins via launching a discrete signaling network in cancer. Subsequently, we selected a compound from a library of backbone cyclic peptides generated toward the PAR PH binding motif, namely the lead compound, Pc(4-4). Pc(4-4) binds to the PAR PH binding domain and blocks the association of PH-signal proteins, such as Akt or Etk/Bmx with PAR2. It attenuates PAR2 oncogenic activity. The potent inhibitory function of Pc(4-4) is demonstrated via inhibition of ovarian cancer peritoneal spread in mice. While the detection of PAR2 may serve as a predictor for ovarian cancer, the novel Pc(4-4) compound may serve as a powerful medicament in STICs and ovarian cancer. This is the first demonstration of the involvement of PAR PH binding motif signaling in ovarian cancer and Pc(4-4) as a potential therapy treatment.

Preoperative Serum Vascular Endothelial Growth Factor as a predictor of malignant ovarian tumor

Background: Effective biomarkers for accurate characterization of newly diagnosed ovarian tumors and adnexal masses are of paramount importance. The availability of an ideal serum marker is highly recommended. Vascular endothelial growth factor (VEGF) may be considered as a predictor of ovarian cancer. Objective: This study explored the efficacy of preoperative serum VEGF for detection of malignant ovarian tumor. Methods: This cross sectional analytical study was conducted among 86 patients who were enrolled for this study according to final histopathology report and who did not receive any kind of treatment. Serum levels of VEGF-A were determined by using ELISA method. ROC curve was plotted to achieve the best cutoff value of serum VEGF. The Mann-Whitney test was used to compare the VEGF distribution across sub-groups of patients. Result: A statistically significant difference in the levels of serum VEGF level was observed between benign and malignant ovarian tumor patients. Ovarian cancer patients had a higher preoperative median S. VEGF level of 753.8 pg/ml than that of benign ovarian masses (median 241.8 pg/ml; p value 0.001). The ability of serum VEGF to differentiate malignancy from benign masses at a cut-off value of 547.85 pg/ml gave a sensitivity of 90.1%, a specificity of 93.5%. Conclusion: This study revealed that preoperative serum VEGF may be used as a feasible vascular marker and predictor of malignant ovarian tumors. Bangladesh Med Res Counc Bull 2023; 49: 183-189

N6-methyladenosine Methyltransferase METTL3 Enhances PTGER2 Expression to Increase Ovarian Cancer Stemness and Chemoresistance.

Ovarian cancer is the second leading cause of gynecologic cancer-associated deaths. Cancer stemness and chemoresistance are responsible for ovarian cancer metastasis and the poor prognosis of patients. In this study, we determined the function of N6-methyladenine (m6A) RNA methylation and prostaglandin E receptor 2 (PTGER2) in ovarian cancer progression. The m6A RNA methylation-associated PTGER2 in ovarian cancer was identified using bioinformatics analysis. The role of PTGER2 in ovarian cancer was elucidated in cell lines and clinical samples with cellular and molecular experiments. In this investigation, bioinformatics analysis based on a public cancer database was used to elucidate the impact of m6A modification on the prognosis of patients with ovarian cancer. Moreover, PTGER2 was identified as a potential oncogene associated with the distant metastasis of ovarian cancer and poor patient prognosis. Interestingly, PTGER2 expression was experimentally shown to be enhanced by N6-adenosine-methyltransferase 70 kDa subunit (METTL3)-mediated m6A modification. In addition, PTGER2 enhanced cancer stem cell self-renewal properties, the epithelial-mesenchymal transition, and DNA damage repair, thus potentiating cell stemness, therapy resistance to carboplatin, proliferation, and metastasis of ovarian cancer. Importantly, PTGER2 expression in clinical samples was associated with distant metastasis, predicted poor patient prognosis, and independently served as a prognostic predictor in ovarian cancer. Our work defines PTGER2 as an oncogene and reveals that PTGER2 is a prognostic predictor and novel therapeutic target for the management of ovarian cancer.

C-Reactive Protein/Albumin (Crp/Alb) Ratio as a Predictor of Ovarian Cancer

Ovarian cancer is a type of cancer with a high incidence and mortality rate in Indonesia and worldwide. C-reactive protein (CRP) is an inflammatory marker meanwhile albumin is an indicator of nutritional deficiencies in ovarian cancer. This study is a diagnostic test for ovarian cancer in women aged >18 years and without previous history of ovarian cancer who underwent laparotomy or laparoscopy at Prof. Ngoerah General Hospital, Denpasar. Samples were taken by consecutive sampling. CRP examination was carried out in the laboratory by immunoturbidimetry method using the CRP Latex Kit (Roche) and measured using a Cobas integra 501 at a wavelength of 552 nm. The gold standard to diagnosed ovarian cancer was according to histopathological examination. A total of 69 women with ovarian tumors were recruited into the study which consisted of 40 ovarian cancers and 29 benign ovarian tumors. A significantly higher median CRP/Albumin ratio was found in ovarian cancer patients compared to benign ovarian tumors (6.9 vs 0.45; p=0.001). The optimal CRP/albumin ratio cut-off value was 1.34. The diagnostic capability of the CRP/Albumin ratio was found to be the best in diagnosing cancer at an advanced stage with a sensitivity of 86.9%, specificity of 68.9%, PPV of 68.9%, NPV of 86.9%, accuracy of 76.9%, positive likelihood ratio 2.8 and negative likelihood ratio 0.2. CRP/Albumin ratio can a potential diagnostic tool for ovarian cancer especially in advanced stage.

Construction and validation of a novel aging-related gene signature and prognostic nomogram for predicting the overall survival in ovarian cancer.

BackgroundOvarian cancer (OC) is the most lethal gynecological malignancy. The objective of this study was to establish and validate an individual aging‐related gene signature and a clinical nomogram that can powerfully predict independently the overall survival rate of patients with ovarian cancer.MethodsData on transcriptomic profile and relevant clinical information were retrieved from The Cancer Genome Atlas (TCGA) database as a training group, and the same data from three public Gene Expression Omnibus (GEO) databases as validation groups. Univariate Cox regression analysis, lasso regression analysis, and multiple multivariate Cox analysis were analyzed sequentially to select the genes to be included in the aging‐associated signature. A risk scoring model was established and verified, the predictive value of the model was evaluated, and a clinical nomogram was established.ResultsWe found eight genes that were most relevant to prognosis and constructed an eight‐mRNA signature. Based on the model, each OC patient's risk score was able to be calculated and patients were split into groups of low and high risks with a distinct outcome. Survival analysis confirmed that the outcome of patients in the high‐risk group was dramatically shorter than that of those in the low‐risk group, and the eight‐mRNA signature can be considered as a powerful and independent predictor that could predict the outcome of OC patient. Additionally, the risk score and age can be used to construct a clinical nomogram as a simpler tool for predicting prognosis. We also explored the association between the risk score and immunity and drug sensitivity.ConclusionThis study suggested that the aging‐related gene signature could be used as an intervention point and latent prognostic predictor in OC, which may provide new perceptions for postoperative treatment strategies.

Integrated Analysis of Prognostic and Immune Associated Integrin Family in Ovarian Cancer.

Human integrin receptors are important for cell-cell and cell-matrix adhesion in normal epithelial cells. Emerging evidences have indicated integrin members are involved in cancer development and progression as well. However, the expression patterns and clinical significance of the whole integrin family in ovarian cancer (OC) have not yet been well understood. In the present study, we utilized the public datasets including GEPIA, GEO, ONCOMINE, cBioPortal, Kaplan-Meier Plotter, TIMER databases, to analyze the expression and prognostic value of integrin members in OC. We found ITGA3/B4/B6/B7/B8 were abnormally overexpressed in OC; ITGA6 was good prognosis predictor in OC; ITGA3/ B4/B8 were poor prognosis predictor specially in advanced OC patients; elevated ITGA3/B4 might promote metastasis and elevated ITGA3/B8 might promote platinum resistance of OC; ITGA3 and ITGB4 might synergistically or independently regulate cell adhesion and proliferation; ITGA4/AL/AM/AX/B2/B7 showed strong correlations with various tumor immune infiltrates (TILs), especially with pro-tumor immunes cell types like monocyte, M2 macrophage and exhaustion T cells infiltration; ITGAL/AM/B2/B7 and residing memory CD8+ T cells marker ITGAE were specially associated with early OC patients outcome. Our results implied that ITGA3/B4 were important prognostic markers of advanced OC, ITGAL/AM/ B2/B7 were immune associated prognosis markers of early OC, together they might render important therapeutic targets for OC.

Effects of dynein light chain Tctex-type 3 on the biological behavior of ovarian cancer.

ObjectiveTo investigate dynein light chain Tctex-type 3 (DYNLT3) protein expression in ovarian epithelial lesions and explore the effects and related mechanisms of DYNLT3 in terms of the biological behavior of ovarian cancer.Materials and methodsInitially, expression of the DYNLT3 protein in ovarian epithelial lesions was detected by immunohistochemical staining, and the prognostic value of DYNLT3 mRNA expression in ovarian cancer patients was assessed using the Kaplan-Meier plotter database. Then, the mRNA and protein expression of DYNLT3 in IOSE80 normal ovarian epithelial cells and SKOV3 ovarian cancer cells was evaluated by quantitative real-time polymerase chain reaction and Western blotting respectively, and the proliferation, apoptosis, migration and invasion of SKOV3 cells after DYNLT3 over-expression and under-expression were investigated by CCK-8 assays and immunofluorescence staining, flow cytometry, wound healing assays and Transwell invasion assays, respectively. Furthermore, the expression of the proliferation-related proteins PCNA and Ki-67 and the invasion- and migration-related proteins Ezrin, Fascin, MMP2 and MMP9 in cells was examined by Western blotting.ResultsThe protein expression of DYNLT3 gradually increased during the progression of ovarian epithelial lesions, and was related to the development of ovarian cancer. High expression of DYNLT3 mRNA was related to poor overall survival and progression free survival, especially in serous ovarian cancer patients. In addition, overexpression of DYNLT3 promoted SKOV3 cell proliferation, invasion and migration. The corresponding results were also verified by a DYNLT3 knockdown assay. Moreover, DYNLT3 increased cell proliferation, which was related to Ki-67 expression. Besides, DYNLT3 enhanced cell invasion and migration through regulating Ezrin, but not Fascin, MMP2 or MMP9.ConclusionDYNLT3 exerts pro-tumoral effects on ovarian cancer through promoting cell proliferation, migration and invasion, possibly via regulating the protein expression of Ki-67 and Ezrin. DYNLT3 may be a potential prognostic predictor in ovarian cancer.

Peroxiredoxin-5 is a negative survival predictor in ovarian cancer.

Peroxiredoxins (PRDXs) constitute a family of antioxidant enzymes which are also involved in the process of carcinogenesis. They are composed of six identified isoforms (PRDX-1-6) and are supposed to play different roles in tumor progression, depending on type of cancer and member of the PRDX family. The aim of the study was to assess the prog- nostic value of PRDXs in ovarian cancer. a dataset of patients with ovarian cancer from The Cancer Genome Atlas was analyzed. Expression of PRDX-1 to 6 mRNA was evaluated in 260 samples. The prognostic value of PRDXs was assessed using the Cox regression model which included the following clinical and pathological data: age, clinical stage, tumor grade, and residual disease. Within the PRDXs family, only higher expression of PRDX-5 was associated with worse overall survival both, in unselected patients and > 50-year-olds. PRDX-5 expression and residual disease were independent negative prognostic factors of patient survival. PRDX-5 is a negative predictor of survival in ovarian cancer.

Prognostic values of DNA mismatch repair genes in ovarian cancer patients treated with platinum-based chemotherapy

PurposeDNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR has been reported as a prognostic marker in certain cancers; however, the results are controversial. Therefore, identification of the prognostic value of MMR genes in ovarian cancer based on a large sample size is pivotal.MethodsIn the current study, we systemically investigated the prognostic roles of seven MMR genes, MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2, in ovarian cancer patients treated with platinum-based chemotherapy through “The Kaplan–Meier plotter” (KM plotter) database, which contains gene expression data and survival information of ovarian cancer patients.ResultsAmong seven MMR genes, high mRNA levels of MSH6, MLH1 and PMS2 were significantly associated with a better overall survival for all ovarian cancer patients treated with platinum-based chemotherapy, especially in late-stage and poor-differentiated ovarian cancer patients. Increased MSH6 and PMS2 mRNA expression was correlated with a favorable overall survival in serous ovarian cancer patients.ConclusionsOur results indicate that sufficient MMR system is associated with an improved survival in ovarian cancer treated with platinum-based chemotherapy. MMR gene may be a potential prognosis predictor in ovarian cancer.

CD44 standard form expression is correlated with high-grade and advanced-stage ovarian carcinoma but not prognosis

Single-chain glycoprotein CD44 is a major cell surface receptor for hyaluronan and mediates epithelial cell adhesion by its involvement in cell-cell and cell-matrix interactions. Recently, CD44 has been identified as a biomarker of cancer stem cells in many malignancies including ovarian carcinoma. However, its clinical significance in human ovarian carcinoma has been controversial until recently. The aim of our current study was to clarify the clinical role of CD44 expression in human ovarian carcinoma. Immunohistochemical staining of 483 primary ovarian carcinoma and 27 paired primary and recurrent ovarian carcinoma samples for CD44 standard form (CD44s) was performed using tissue microarray. The associations between CD44s expression and clinical factors (histologic types, tumor grade, International Federation of Gynecology and Obstetrics stage, and response to chemotherapy), and overall or disease-free survivals were analyzed. We observed CD44s expression in 38% of the ovarian carcinoma samples. Results of the Fisher exact test suggested that CD44s expression was associated with high-grade carcinoma (P = .013), advanced International Federation of Gynecology and Obstetrics stage (III-IV; P < .001), age at diagnosis less than 60 years (P = .011), and transitional cell carcinoma (P = .039). However, CD44s expression was not associated with overall survival (P = .529) or disease-free survival (P = .218) by the log-rank test. Moreover, there was no statistical difference in CD44s expression between the primary and recurrent ovarian carcinomas. Our results showed that CD44s expression is not a prognostic predictor in ovarian cancer.

Myofibrillogenesis regulator 1 (MR-1) is a novel biomarker and potential therapeutic target for human ovarian cancer

BackgroundMyofibrillogenesis regulator 1 (MR-1) is overexpressed in human cancer cells and plays an essential role in cancer cell growth. However, the significance of MR-1 in human ovarian cancer has not yet been explored. The aim of this study was to examine whether MR-1 is a predictor of ovarian cancer and its value as a therapeutic target in ovarian cancer patients.MethodsReverse-transcription polymerase chain reaction (PCR) and quantitative real-time PCR were used to detect MR-1 mRNA levels in tissue samples from 26 ovarian cancer patients and 25 controls with benign ovarian disease. Anti-MR-1 polyclonal antibodies were prepared, tested by ELISA and western blotting, and then used for immunohistochemical analysis of the tissue samples. Adhesion and invasion of 292T cells was also examined after transfection of a pMX-MR-1 plasmid. Knockdown of MR-1 expression was achieved after stable transfection of SKOV3 cells with a short hairpin DNA pGPU6/GFP/Neo plasmid against the MR-1 gene. In addition, SKOV3 cells were treated with paclitaxel and carboplatin, and a potential role for MR-1 as a therapeutic target was evaluated.ResultsMR-1 was overexpressed in ovarian cancer tissues and SKOV3 cells. 293T cells overexpressed MR-1, and cellular spread and invasion were enhanced after transfection of the pMX-MR-1 plasmid, suggesting that MR-1 is critical for ovarian cancer cell growth. Knockdown of MR-1 expression inhibited cell adhesion and invasion, and treatment with anti-cancer drugs decreased its expression in cancer cells. Taken together, these results provide the first evidence of the cellular and molecular mechanisms by which MR-1 might serve as a novel biological marker and potential therapeutic target for ovarian cancer.ConclusionsMR-1 may be a biomarker for diagnosis of ovarian cancer. It may also be useful for monitoring of the effects of anti-cancer therapies. Further studies are needed to clarify whether MR-1 is an early diagnostic marker for ovarian cancer and a possible therapeutic target.

Global Role of the Immune System in Identifying Cancer Initiation and Limiting Disease Progression

The field of tumor immunology has undergone a significant scientific evolution during the last decade. We now know that human cancer is immunogenic, and we have identified a multitude of tumor-related proteins that stimulate immunity in cancer patients. Highly quantitative and reproducible methods for measuring immunity have been developed and have allowed a more complete delineation of the tumor-associated immune response. Functional antitumor immunity requires a response initiated by potent antigen-presenting cells, such as dendritic cells, and the engagement of a variety of effector cells—not only cytotoxic T cells, but also T-helper cells and B cells, which initiate antibody immunity. Finally, mechanisms of immune escape increasingly are being determined. Cancer evasion of the immune system is not only related to immunosuppressive factors secreted by the tumor and surrounding stroma, but is also aided by the fact that most tumor antigens are self-proteins. Self-proteins, as cancer antigens, impede the generation of robust immunity via toleragenic mechanisms, such as the elaboration of T-regulatory cells, which function to prevent autoimmunity and limit inflammation. The result of these advances in the laboratory is the development of immunotherapeutic strategies that are targeted, are tailored for specific disease burdens, and directly address mechanisms of immune system failure. The studies presented in this issue of the Journal of Clinical Oncology represent the diversity of clinical applications that are now possible when contemplating immune-based strategies for cancer patients. There is abundant evidence that tumor-specific immunity is present even in early-stage cancers. Human antibodies specific for tumor-related proteins, which are used to probe expression libraries developed from tumor cells, are an effective tool for identifying antigens. Recent data suggest that antibody immunity is so prevalent in cancer patients that an immunologic signature that would predict those who will develop cancer can be identified. Screening sera from prostate cancer patients and controls against 22 immunogenic peptides derived from prostate cancer tissue was a more sensitive test than the measurement of serum prostate-specific antigen levels for discriminating individuals with cancer from controls. Furthermore, evidence of an adaptive immune response at the site of a tumor has been shown to impact prognosis. Zhang et al demonstrated that infiltrating T cells observed in ovarian cancer tumors could be characterized as intratumoral or stromal. Those patients with T cells clearly invading the tumor bed had a significantly improved prognosis as compared with individuals whose T-cell infiltrates were located in the stroma. This survival benefit transcended optimal surgical debulking, a critical outcome predictor in ovarian cancer. Analysis of inflammatory infiltrates in non–small-cell lung cancer, presented in this issue of the Journal, demonstrates striking similarities to the observations in ovarian cancer, albeit with a measure of an innate immune response: the macrophage. Macrophage infiltrates could be detected in both tumor islets and the tumor stroma of non–small-cell lung cancers. Increasing macrophage density in tumor islets was an independent favorable prognostic indicator, whereas increasing macrophage stromal density was an independent predictor of reduced survival. The survival benefit associated with macrophage-infiltrating tumor cell islets was discernable even in those patients who had an incomplete resection of their tumor. These patients had a longer survival than those patients whose tumors were completely resected and had evidence of only low intratumoral macrophage infiltration. Such studies lay the foundation for diagnostic and prognostic approaches utilizing VOLUME 23 d NUMBER 35 d DECEMBER 1

Pelvic examination, transvaginal ultrasound and transvaginal color Doppler sonography as predictors of ovarian cancer

Objective: To assess and compare the efficacy of pelvic examination, transvaginal ultrasound and transvaginal color Doppler imaging in differentiating benign and malignant ovarian tumors. Methods: 34 patients with ovarian tumors scheduled for laparotomy underwent pelvic examination and a diagnosis of benign or malignant tumor was made. Transvaginal ultrasound was carried out to study the ovarian morphology followed by color Doppler imaging. A score of ≥9 on Sassone scoring system or a pulsatility index <1 was taken as suspicious for malignancy. Results: Of all the three indicators (pelvic examination, transvaginal sonography and Doppler) transvaginal sonography had the highest sensitivity (100%) and Doppler had maximum specificity (96.29%) for predicting malignancy. However, statistical analysis did not show any difference in the predicting ability of these three modalities. Conclusion: Pelvic examination, transvaginal sonography and Doppler all had similar ability to predict malignancy in an adnexal mass.