Detection of OPCML methylation, a possible epigenetic marker, from free serum circulating DNA to improve the diagnosis of early-stage ovarian epithelial cancer.
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ABSTRACT:
SUBMITTER: Wang B
PROVIDER: S-EPMC5494804 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:The aim of the study was to develop a new diagnostic biomarker for identifying serum exosomal miRNAs specific to epithelial ovarian cancer (EOC) and to find out target gene of the miRNA for exploring the molecular mechanisms in EOC. A total of 84 cases of ovarian masses and sera were enrolled, comprising EOC (n = 71), benign ovarian neoplasms (n = 13). We detected expression of candidate miRNAs in the serum and tissue of both benign ovarian neoplasm group and EOC group using real-time polymerase chain reaction. Immunohistochemistry were constructed using formalin fixed paraffin embedded (FFPE) tissue to detect expression level of suppressor of cytokine signaling 4 (SOCS4). In the EOC group, miRNA-1290 was significantly overexpressed in serum exosomes and tissues as compared to benign ovarian neoplasm group (fold change ≥ 2, p < 0.05). We observed area under the receiver operating characteristic curve (AUC) for miR-1290, using a cut-off of 0.73, the exosomal miR-1290 from serum had AUC, sensitivity, and specificity values of 0.794, 69.2 and 87.3, respectively. In immunohistochemical study, expression of SOCS4 in EOC was lower than that in benign ovarian neoplasm. Serum exosomal miR-1290 could be considered as a biomarker for differential diagnosis of EOC from benign ovarian neoplasm and SOCS4 might be potential target gene of miR-1290 in EOC.
| S-EPMC8928998 | biostudies-literature
Project description:BackgroundCirculating tumor DNA (ctDNA) is a promising diagnostic and prognostic marker for many cancers and has been actively investigated in recent years. Previous studies have already demonstrated the potential use of ctDNA methylation markers in the diagnosis and prognostication of colorectal cancer (CRC). This retrospective study validated the value of methylation biomarker MYO1-G (cg10673833) in CRC diagnosis and disease monitoring using digital droplet PCR (ddPCR), a biomarker selected from our previous study due to its highest diagnostic efficiency.MethodsBlood samples of CRC and control samples from tumor-free individuals at two institutions were collected to quantify the methylation ratio using ddPCR. Area under curve (AUC) was calculated after constructing receiver operating characteristic curve (ROC) for CRC diagnosis. Sensitivity and specificity were estimated and comparisons of methylation ratio in different groups were performed.ResultsWe collected 673 blood samples from 272 patients diagnosed with stage I-IV CRC and 402 normal control samples. The methylation biomarker discriminated patients with CRC from normal controls with high accuracy (area under curve [AUC] = 0.94) and yielded a sensitivity of 84.3% and specificity of 94.5%. Besides, methylation ratio of MYO1-G was associated with tumor burden and treatment response. The methylation ratio was significantly lower in patients after their radical operation than when compared with those before surgeries (P < 0.001). Methylation ratio was significantly higher in patients with disease progression than those with stable disease (P = 0.002) and those with complete response or partial response (P = 0.009).ConclusionsTogether, our study indicated that this methylation marker can serve as a potential biomarker for diagnosing and monitoring CRC.
| S-EPMC8713401 | biostudies-literature
Project description:BackgroundEsophageal cancer (ECa) is one of the most deadly cancers, with increasing incidence worldwide and poor prognosis. While endoscopy is recommended for the detection of ECa in high-risk individuals, it is not suitable for large-scale screening due to its invasiveness and inconvenience.MethodsIn this study, a novel gene methylation panel was developed for a blood-based test, and its diagnostic efficacy was evaluated using a cohort of 304 participants (203 cases, 101 controls). The assessment focused on the DNA methylation levels of SEPTIN9, tissue factor pathway inhibitor 2 (TFPI2), and the fragile histidine triad gene (FHIT) in patients with ECa, benign esophageal disease, and healthy controls. The receiver operating characteristic (ROC) curve was generated for the panel to calculate the area under the curve (AUC), sensitivity, specificity, and 95% confidence intervals (CIs), along with a comparison to the gold standard of pathological examination. The consistency between biomarker and pathological diagnosis was evaluated with kappa analysis conducted with IBM SPSS Statistics. The Chi-square test or Fisher's exact test was utilized to assess the association of test positivity with demographic characteristics.ResultsIn patients with ECa, SEPTIN9, TFPI2, and FHIT DNA methylation levels were significantly higher compared to those with benign esophageal disease or healthy controls. The panel demonstrated promising potential as a noninvasive tool for distinguishing malignant tumors from both healthy controls and benign esophageal diseases, achieving an area under the ROC curve of 0.925 (95% CI: 0.889-0.952), with a sensitivity of 79.8% [95% CI 73.6-85.1%] and specificity of 95.0% [95% CI 88.8-98.4%]. In particular, the panel showed exceptional diagnostic efficiency for stage 0, I, and II cancer patients with sensitivity at 69.0, 75.5%, and 78.9%, respectively. The comparison revealed a Kappa value of 0.725 between RT-PCR testing and the established gold standard of pathological examination, indicating a high level of consistency. Additionally, there was no bias in diagnostic efficiency based on age, gender, or the presence of other malignancies (non-esophageal cancers).ConclusionsThe study's findings suggested that the DNA methylation biomarkers panel holds promise as a non-invasive and convenient diagnostic test for ECa. The panel's ability to distinguish malignant tumors from benign esophageal diseases, coupled with its high sensitivity and specificity, presented opportunities to enhance the over-all diagnosis of high-risk population when in conjunction with existing detection methods.
| S-EPMC11670433 | biostudies-literature
Project description:BackgroundNo residual disease (CC 0) following cytoreductive surgery is pivotal for the prognosis of women with advanced stage epithelial ovarian cancer (EOC). Improving CC 0 resection rates without increasing morbidity and no delay in subsequent chemotherapy favors a better outcome in these women. Prerequisites to facilitate this surgical paradigm shift and subsequent ramifications need to be addressed. This quality improvement study assessed 559 women with advanced EOC who had cytoreductive surgery between January 2014 and December 2019 in our tertiary referral centre. Following implementation of the Enhanced Recovery After Surgery (ERAS) pathway and prehabilitation protocols, the surgical management paradigm in advanced EOC patients shifted towards maximal surgical effort cytoreduction in 2016. Surgical outcome parameters before, during, and after this paradigm shift were compared. The primary outcome measure was residual disease (RD). The secondary outcome parameters were postoperative morbidity, operative time (OT), length of stay (LOS) and progression-free-survival (PFS).ResultsR0 resection rate in patients with advanced EOC increased from 57.3% to 74.4% after the paradigm shift in surgical management whilst peri-operative morbidity and delays in adjuvant chemotherapy were unchanged. The mean OT increased from 133 + 55 min to 197 + 85 min, and postoperative high dependency/intensive care unit (HDU/ICU) admissions increased from 8.1% to 33.1%. The subsequent mean LOS increased from 7.0 + 2.6 to 8.4 + 4.9 days. The median PFS was 33 months. There was no difference for PFS in the three time frames but a trend towards improvement was observed.ConclusionsImproved CC 0 surgical cytoreduction rates without compromising morbidity in advanced EOC is achievable owing to the right conditions. Maximal effort cytoreductive surgery should solely be carried out in high output tertiary referral centres due to the associated substantial prerequisites and ramifications.
| S-EPMC10638711 | biostudies-literature
Project description:EphA8 is one of the Eph receptors in the Eph/ephrin receptor tyrosine kinase (RTK) subfamily. During tumorigenesis, EphA8 is involved in angiogenesis, cell adhesion and migration. In this study, we determined the mRNA and protein expression levels of EphA8 in cancerous and normal ovarian tissue samples by quantitative reverse transcription PCR (qRT-PCR) (N = 60) and tissue microarray immunohistochemistry analysis (TMA-IHC) (N = 223) respectively. EphA8 protein levels in cancer tissues were correlated with epithelial ovarian cancer (EOC) patients' clinical characteristics and overall survival. Both EphA8 mRNA and protein levels were significantly higher in EOC tissues than in normal or benign ovarian tissues (all P < 0.05). High EphA8 protein level was associated older age at diagnosis, higher FIGO stage, positive lymph nodes, presence of metastasis, positive ascitic fluid, and higher serum CA-125 level. High EphA8 protein level is an independent prognostic marker in EOC. We conclude that EphA8 acts as an oncogene in EOC development and progression. Detection of EphA8 expression could be a useful prognosis marker and targeting EphA8 represents a novel strategy for EOC treatment.
| S-EPMC4991493 | biostudies-literature
Project description:BackgroundOne fifth of patients with epithelial ovarian cancers (EOC) present at an early stage (FIGO stage I & II). However, there is scarcity of literature on the outcomes and its predictors. The aim of the study was to assess relapse free survival (RFS), overall survival (OS) and its predictors in early stage EOC.Patients and methodsIn this retrospectively study, we included all patients with early-stage EOC diagnosed between January 2010 and December 2018. Patients with synchronous malignancies were excluded. Clinical profile, clinico-pathological characteristics and treatment details were recorded. Patient underwent initial surgery followed by adjuvant chemotherapy in high-risk disease. Patients with stage IC, or stage II or clear cell histology or high-grade histology irrespective of stage/histological subtype were defined as high-risk disease. Fertility sparing surgery (FSS) [unilateral salpingo-oopherectomy with complete surgical staging] was performed in patient willing to preserve fertility. Primary objective was to assess RFS and OS in all patients with early stage EOC. Secondary objectives were to assess RFS and OS in early stage EOC with high-risk disease, predictors of RFS and OS, and outcomes of FSS. Survival probabilities were estimated according to Kaplan-Meier and compared by the log rank test. Cox's regression model was used to analyze the significance of various factors affecting relapse free survival (RFS) and overall survival (OS).Results195 patients with early stage EOC were recruited with median age of 47 years (range, 16-80 years). FIGO stage I and stage II were seen in 72 % and 18 % patients respectively. Serous subtype was reported in 58 % and high-grade histology in 66 %. 184 patients (94.0%) underwent optimal staging surgery, including 27 (14%) with fertility sparing surgery (FSS). 133 (91.7 %) of 145 patients with high-risk disease received adjuvant chemotherapy (paclitaxel and carboplatin), while 12 (8.3 %) patients opted to remain on observation. At median follow up of 56 months (95 % CI, 46-64 months), 49 (25 %) patients relapsed [including 3 of 27 (11.1 %) who underwent FSS], 18 patients died of progressive disease, while 31 patients were alive and disease free. Estimated OS at 5 years is 87.6 % (95 % CI 79.9-92.5) and RFS is 73.2 % (95 % CI 64.7-80.0). On multivariate analysis tumor grade was predictive of RFS (HR 2.9, p < 0.04) and OS (HR 9.4, p < 0.02).ConclusionsThis study confirms the excellent outcome for patients with early stage EOC. Histological grade of tumor is a significant predictor of OS and RFS. FSS is feasible in selected patients with early EOC.
| S-EPMC9583112 | biostudies-literature
Project description:We aimed to determine prognostic factors of early stage (I/II) epithelial ovarian carcinoma (EOC) including clinicopathologic and chemotherapeutic regimens. Four hundred and thirty-seven women who underwent primary staging surgery with adjuvant chemotherapy between January 1, 2000 and December 31, 2010 were retrospectively reviewed and analyzed from two medical centers. The prognostic factors were determined from multivariate survival analyses using Cox regression models. The majority of women were diagnosed with stage Ic (244/437, 55.8%). The histopathologic types were clear cell (37.5%), endometrioid (27.2%), serous (14.0%), and mucinous (13.3%). Fifty-seven percent (249/437) of the women received taxane-based (platinum plus paclitaxel) regimens and 43.0% received non-taxane (platinum plus cyclophosphamide) regimens as frontline adjuvant chemotherapy. Clear cell tumors (adjusted Hazard ratio (aHR) 0.37, 95% confidence interval (CI) 0.21⁻0.73, p = 0.001) showed better 5-year disease-free survival (DFS) than serous tumors. Women diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage II (aHR 5.97, 95% CI = 2.47⁻14.39, p < 0.001), grade 3 tumor without clear cell (aHR 2.28, 95% CI = 1.02⁻5.07, p = 0.004) and who received 3⁻5 cycles of non-taxane regimens (aHR 3.29, 95% CI = 1.47⁻7.34, p = 0.004) had worse 5-year overall survival (OS). Clear cell histology treated with taxane-based regimens showed significantly higher 5-year DFS (91.2% vs. 82.0%, aHR = 0.45, 95% CI = 0.21⁻0.93, p = 0.043) and 5-year OS (93.5% vs. 79.0%, aHR = 0.30, 95% CI = 0.13⁻0.70, p = 0.005) than those treated with non-taxane-based regimens. We conclude that stage, tumor grade, and chemotherapeutic regimens/cycles are independent prognostic factors for early stage ovarian cancer.
| S-EPMC6406698 | biostudies-literature
Project description:BackgroundMany tumor-derived endothelial cells (TECs) are shed into the blood and turn into circulating TECs (CTECs). Rare circulating non-hematologic aneuploid cells contain CTCs and CTECs, which are biologically and functionally different from each other. CD31 is one of the most representative endothelial cell (EC) markers, yet CD31 alone is not sufficient to detect malignant CTECs due to the existence of abundant normal ECs in circulation. Aneuploidy of chromosome 8 (CEP8) is an important criterion for the identification of malignant cells. Combined in situ phenotypic and karyotypic characterization, which includes an examination of both protein expression and aneuploid chromosomes, has demonstrated its unique advantage for both effective distinguishing and comprehensive detection of CTCs and CTECs.MethodsA total of 98 subjects were recruited in the current study, including healthy donors and patients with benign disease and early-stage non-small-cell lung cancer (NSCLC). SE-iFISH was performed to quantitatively analyze diverse subtypes of aneuploid CD31+ CTECs and CD31- CTCs classified upon the ploidy of chromosome 8 and tumor marker expression in the specimens collected from the recruited subjects.ResultsCD31- CTCs primarily consist of triploid CTCs with a small cell size (≤5 µm) and large hyperploid CTCs (≥ pentaploid), whereas CD31+ CTECs are mainly comprised of large hyperploid cells. Enumeration of the total numbers of both CTCs and CTECs might help identify malignant nodules with a high sensitivity, whereas quantification of tetraploid CTCs and CTECs specifically exhibited a high specificity for the identification of malignant nodules.ConclusionsCombined detection of the specific subtypes of aneuploid CD31+ CTECs and CD31- CTCs may help to effectively identify malignant nodules with a higher sensitivity and specificity in early stage NSCLC patients.
| S-EPMC7418803 | biostudies-literature
Project description:BACKGROUND:Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer. METHODS:We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1?, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNF?, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer. RESULTS:We observed a trend across quartiles for IL-2 (OR(Q4 vs. Q1): 1.57, 95% CI: 0.98-2.52, P = 0.07), IL-4 (OR(Q4 vs. Q1): 1.50, 95% CI: 0.95-2.38, P = 0.06), IL-6 (OR(Q4 vs. Q1): 1.63, 95% CI: 1.03-2.58, P = 0.03), IL-12p40 (OR(Q4 vs. Q1): 1.60, 95% CI: 1.02-2.51, P = 0.06), and IL-13 (OR(Q4 vs. Q1): 1.42, 95% CI: 0.90-2.26, P = 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (P trend = 0.01), IL-6 (P trend = 0.01), IL-12p40 (P trend = 0.01), and IL-13 (P trend = 0.04). ORs were not materially different after excluding cases diagnosed less than 5 years after blood donation or when limited to serous tumors. CONCLUSIONS AND IMPACT:This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development of this disease.
| S-EPMC3089656 | biostudies-literature
Project description:Failure to detect early-stage epithelial ovarian cancer (EOC) is a major contributing factor to its low survival rate. Increasing evidence suggests that different subtypes of EOC may behave as distinct diseases due to their different cells of origins, histology and treatment responses. Therefore, the identification of EOC subtype-specific biomarkers that can early detect the disease should be clinically beneficial. Exosomes are extracellular vesicles secreted by different types of cells and carry biological molecules, which play important roles in cell-cell communication and regulation of various biological processes. Multiple studies have proposed that exosomal miRNAs present in the circulation are good biomarkers for non-invasive early detection of cancer. In this review, the potential use of exosomal miRNAs as early detection biomarkers for EOCs and their accuracy are discussed. We also review the differential expression of circulating exosomal miRNAs and cell-free miRNAs between different biofluid sources, i.e., plasma and serum, and touch on the issue of endogenous reference miRNA selection. Additionally, the current clinical trials using miRNAs for detecting EOCs are summarized. In conclusion, circulating exosomal miRNAs as the non-invasive biomarkers have a high potential for early detection of EOC and its subtypes, and are likely to be clinically important in the future.
| S-EPMC8533168 | biostudies-literature