Diagnostic value of HE4+ circulating tumor cells in patients with suspicious ovarian cancer.
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ABSTRACT:
SUBMITTER: Guo YX
PROVIDER: S-EPMC5800921 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:tRNA-derived small non-coding RNAs (tsncRNAs), a class of newly defined small non-coding RNA, have been considered to be involved in various cellular biological processes through regulating gene expression at both transcriptional and post-transcriptional level. However, the presence of circulating tsncRNAs and their diagnostic potential is largely unclear. In this study, we investigate the serum-derived public transcriptome data from ovarian tumor patients and non-cancer controls, and find that circulating tsncRNAs cover a high proportion of total small RNA and are non-random degradation products in serum (ranging from 2.5-29.4%), which are enriched in several specific types of related tRNA (e.g., Gly-tRNA). Particularly, four tsncRNAs are differentially expressed in serum from cancer patients compared to those from healthy controls, and can predict abnormal cell proliferation with high accuracy. Our results reveal the ubiquitous presence of circulating tsncRNAs in serum, and diagnostic potential of specific tsncRNAs for ovarian tumor.
| S-EPMC6251159 | biostudies-literature
Project description:BackgroundThe prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer.Materials and methodsA literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted.ResultsThis meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22-2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18-1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34-3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45-2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62-1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87-8.85).ConclusionOur study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer.
| S-EPMC4476582 | biostudies-literature
Project description:ObjectiveSurvival in epithelial ovarian cancer (EOC) remains poor. Most patients are diagnosed in late stages. Early diagnosis increases the chance of survival. We used the proximity extension assay from Olink Proteomics to search for new protein biomarkers with the potential to improve the diagnostic performance of CA125 and HE4 in patients with ovarian tumors.Material and methodsPlasma samples were obtained from 180 women with ovarian tumors; 30 cases of benign tumor, 28 cases with borderline tumors, 25 early EOC cases (FIGO stage I) and 97 advanced EOC cases (FIGO stages II-IV). Proteins were measured using the Olink® Oncology II and Inflammation panels. For statistical analyses, patients were categorized into benign tumors versus cancer and benign tumors versus borderline + cancer, respectively.ResultsWe analyzed 177 biomarkers. Thirty-four proteins had ROC AUC > 0.7 for discrimination between benign tumors and cancer. Fifteen proteins had ROC AUC > 0.7 for discrimination between benign tumors and borderline tumors + cancer. HE4 ranked highest for both comparisons. A reference model with HE4, CA125 and age (AUC 0.838 for benign tumors vs. cancer and AUC 0.770 for benign tumors vs. borderline tumors + cancer) was compared to the reference model with the addition of each of the remaining proteins with AUC > 0.7. ITGAV was the only individual biomarker found to improve diagnostic performance of the reference model, to AUC 0.874 for benign tumors vs. cancer and AUC 0.818 for benign tumors vs. borderline tumors + cancer (p < 0.05). Cross-validation and LASSO regression was combined to select multiple biomarker combinations. The best performing model for discrimination between benign tumors and borderline tumors + cancer was a 6-biomarker combination (HE4, CA125, ITGAV, CXCL1, CEACAM1, IL-10RB) and age (AUC 0.868, sensitivity 0.86 and specificity 0.82, p = 0.016 for comparison with the reference model).ConclusionHE4 was the best performing individual biomarker for discrimination between benign ovarian tumors and EOC including borderline tumors. The addition of other carcinogenesis-related biomarkers in a multiplex biomarker panel can improve the diagnostic performance of the established biomarkers HE4 and CA125.
| S-EPMC7571712 | biostudies-literature
Project description:PurposeLow-dose computed tomography (LDCT) screening of high-risk patients decreases lung cancer-related mortality. However, high false-positive rates associated with LDCT result in unnecessary interventions. To distinguish non-small-cell lung cancer (NSCLC) from benign nodules, in the present study, we integrated cellular liquid biomarkers in patients with suspicious lung nodules (lung cancer screening reporting and data system [Lung-RADS] 4).MethodsProspectively, 7.5 mL of blood was collected from 221 individuals (training set: 90 nonscreened NSCLC patients, 74 high-risk screening patients with no/benign nodules [Lung-RADS 1-3], and 20 never smokers; validation set: 37 patients with suspicious nodules [Lung-RADS 4]). Circulating tumor cells (CTCs), CTC clusters, and tumor-macrophage fusion (TMF) cells were identified by blinded analyses. Screening patients underwent a median of two LDCTs (range, 1-4) with a median surveillance time of 30 (range, 11-50) months.ResultsIn the validation set of 37 Lung-RADS 4 patients, all circulating cellular biomarker counts (P < .005; Wilcoxon test) and positivity rates were significantly higher in 23 biopsy-proven NSCLC patients (CTCs: 23 of 23 [100%], CTC clusters: 6 of 23 [26.1%], and TMF cells: 15 of 23 [65.2%]) than in 14 patients with biopsy-proven benign nodules (6 of 14 [42.9%], 0 of 14 [0%], and 2 of 14 [14.3%]). On the basis of cutoff values from the training set, logistic regression with receiver operating characteristic and area under the curve analyses demonstrated that CTCs (sensitivity: 0.870, specificity: 1.0, and area under the curve: 0.989) and TMF cells (0.652; 0.880; 0.790) complement LDCT in diagnosing NSCLC in Lung-RADS 4 patients.ConclusionCellular liquid biomarkers have a potential to complement LDCT interpretation of suspicious Lung-RADS 4 nodules to distinguish NSCLC from benign lung nodules. A future prospective, large-scale, multicenter clinical trial should validate the role of cellular liquid biomarkers in improving diagnostic accuracy in high-risk patients with Lung-RADS 4 nodules.
| S-EPMC9012602 | biostudies-literature
Project description:Circulating tumor cells (CTCs) serve as valuable biomarkers. However, MutL homolog 1 (MLH1)-negative CTCs and their clinical significance in lung cancer are nearly unknown.Here, bioinformatic analysis of MLH1 expression and its clinical significance was conducted using the Oncomine, Ualcan, and Kaplan-Meier plotter websites. Size-based isolation and RNA in situ hybridization assays were used to identify CTCs and evaluate MLH1 and mesenchymal marker expression in CTCs. MLH1 was downregulated in lung cancer patients. Patients with lower MLH1 expression levels had worse prognoses. In a cohort of 32 randomly selected patients with lung cancer, the patients with poorer treatment responses had more MLH1-negative CTCs. The total CTCs, MLH1-negative CTCs and mesenchymal markers-expressing CTCs levels were negatively correlated with prognosis in the lung cancer patients.Our data showed the clinical significance of MLH1 expression in lung cancer tissues. The characterization and numeration of CTCs based on the expression of MLH1 and mesenchymal markers may be a convenient approach for predicting treatment response and prognosis in lung cancer.
| S-EPMC6636948 | biostudies-literature
Project description:Circulating tumour cells (CTCs) have potential utility in various clinical applications for cancer management. The present study focused on evaluating the diagnostic role of CTCs in colorectal cancer (CRC). A total of 89 blood samples from 59 patients diagnosed with CRC and 30 healthy individuals were collected for CTC detection. The Cyttel method is an improved CTC detection strategy, which combines negative enrichment with immunofluorescence and fluorescence in situ hybridization. This method effectively detected a significant increase in total CTCs in patients with CRC (49/59) compared with those in healthy controls (3/30). A cut-off value of 2 CTCs/3.2 ml blood yielded a sensitivity of 83.05% and a specificity of 100%. Additionally, three traditional serum tumour markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4, were examined by immunoassays. The diagnostic sensitivity of CTCs was much higher than that of CEA, CA19-9 and CA72-4 alone or in combination, particularly in patients with early stage CRC. The combined sensitivity of CTCs and CEA reached 91.53%, which was only slightly lower than the sensitivity of all four markers combined (CTCs + CEA + CA19-9 + CA72-4). CTCs with aneuploidy of chromosome 7 or 8 were carefully distinguished, and the associations among different types of CTCs, clinicopathological characteristics and overall survival were statistically analysed. Total CTCs were revealed to be significantly associated with tumour differentiation and nerve invasion. CTCs were more likely to be detected in poorly differentiated CRC tumours than in well- and moderately-differentiated tumours (P=0.026). Furthermore, to the best of our knowledge, the present study was the first to report that CTCs with multiploidy of chromosome 7 were significantly associated with TNM stage. These CTCs exhibited a high chance of being identified in the peripheral blood of patients with late-stage CRC (stage III-IV; P=0.031). The present study suggests that the combination of CTCs and CEA may serve as an effective potential diagnostic and prognostic indicator in patients with CRC. Detection of CTCs with aneuploidy may have increased specificity in predicting highly malignant and invasive tumours in CRC management.
| S-EPMC7285991 | biostudies-literature
Project description:Circulating tumor cells (CTCs) are promising biomarkers for diagnosis and therapy in systemic cancer. However, their infrequent and unreliable detection, especially in nonmetastatic cancer, currently impedes the clinical use of CTCs. Because leukapheresis (LA) targets peripheral blood mononuclear cells, which have a similar density to CTCs, and usually involves processing the whole circulating blood, we tested whether LA could substantially increase CTC detection in operable cancer patients. Therefore, we screened LA products generated from up to 25 L of blood per patient in two independent studies, and found that CTCs can be detected in more than 90% of nonmetastatic breast cancer patients. Interestingly, complete white blood cell sampling enabled determining an upper level for total CTC numbers of about 100,000 cells (median, 7,500 CTCs) per patient and identified a correlation of CTC numbers with anatomic disease spread. We further show that diagnostic leukapheresis can be easily combined with the US Food and Drug Administration-approved CellSearch system for standardized enumeration of CTCs. Direct comparison with 7.5 mL of blood revealed a significantly higher CTC frequency in matched LA samples. Finally, genomic single-cell profiling disclosed highly aberrant CTCs as therapy-escaping variants in breast cancer. In conclusion, LA is a clinically safe method that enabled a reliable detection of CTCs at high frequency even in nonmetastatic cancer patients, and might facilitate the routine clinical use of CTCs as in the sense of a liquid biopsy. Combined with technologies for single-cell molecular genetics or cell biology, it may significantly improve prediction of therapy response and monitoring of early systemic cancer.
| S-EPMC3799344 | biostudies-literature
Project description:Lung cancer is the leading cause of cancer-related deaths globally. Early detection of lung cancer can lead to more effective treatment and improved survival. Circulatory abnormal cells (CACs) with specific chromosomal variation may be used to diagnose lung cancer and to differentiate benign from malignant nodules. The value of CAC in precancer diagnosis, however, remains controversial. In this study, a systematic review and meta-analysis are conducted to clarify the diagnostic value of CAC in early-stage lung cancer. A systematic literature search was conducted using the following medical topic title terms and text-free words: "circulating genetically abnormal cells", "CACs", "liquid biopsy", "early lung cancer", "non-small cell lung cancer", "diagnostic accuracy", "sensitivity" and "specificity" in Science Direct, CNKI and Wanfang databases, respectively. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve were analyzed by STATA15.0 (MP) software. Deek funnel plots were used to assess potential publication bias. Heterogeneity was tested using the I2 statistic and the Cochrane Q test. 7 major studies were included in this meta-analysis, and a total of 53728 participants were analyzed. In the diagnosis of early lung cancer, CAC had pooled sensitivity, specificity, and receiver operating characteristics of 0.80 (95% CI: 0.73-0.86), 0.85 (95% CI: 0.69-0.94), and 0.87 (95% CI: 0.84-0.90). The combined positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and diagnostic score were 23.36 (95% CI: 7.33-74.46), 5.42 (95% CI: 2.37-12.43), 0.23 (95% CI: 0.16-0.35) and 3.15 (95% CI: 1.99-4.31) respectively. Publication bias was not detected. The CAC is effective at detecting lung cancer in its early stages.
| S-EPMC10164803 | biostudies-literature
Project description:Selective overexpression of Human epididymal secretory protein E4 (HE4) points to a role in ovarian cancer tumorigenesis but little is known about the role the HE4 gene or the gene product plays. Here we show that elevated HE4 serum levels correlate with chemoresistance and decreased survival rates in EOC patients. HE4 overexpression promoted xenograft tumor growth and chemoresistance against cisplatin in an animal model resulting in reduced survival rates. HE4 displayed responses to tumor microenvironment constituents and presented increased expression as well as nuclear translocation upon EGF, VEGF and Insulin treatment and nucleolar localization with Insulin treatment. HE4 interacts with EGFR, IGF1R, and transcription factor HIF1α. Constructs of antisense phosphorothio-oligonucleotides targeting HE4 arrested tumor growth in nude mice. Collectively these findings implicate increased HE4 expression as a molecular factor in ovarian cancer tumorigenesis. Selective targeting directed towards the HE4 protein demonstrates therapeutic benefits for the treatment of ovarian cancer.
| S-EPMC3880958 | biostudies-literature
Project description:Background: Studies have shown that circulating tumor DNA (ctDNA) indicates a poor prognosis in ovarian cancer. In this study, meta-analysis was used to assess the relationship between ctDNA and the prognosis of patients with epithelial ovarian cancer. Methods: The clinical trials included in this study were obtained via a search of PubMed, the Cochrane Library, the Web of Science and Embase between the period of establishment and March 2020. We selected clinical studies using qualitative or quantitative ctDNA methods to analyse the prognosis of ovarian epithelial cancer, screened the studies according to the determined inclusion and exclusion criteria, and used the modified JADAD score scale and NOS scale for evaluation, with OS (overall survival) and PFS (progression-free survival) as end events. The Cochrane Evaluation Tool was used to evaluate the quality of the randomized controlled trials. Stata 15.0 software was used to combine the effect ratio (hazard ratio, HR) and its 95% confidence interval (CI). In addition, a source analysis of ctDNA specimens, an analysis of ctDNA detection methods and a subgroup and sensitivity analysis of FIGO staging were performed. Results: A total of 8 studies were included in this meta-analysis, and ctDNA was found to be an independent risk factor for patients with epithelial ovarian cancer (OS: HR = 2.36, 95% CI [1.76,3.17], P < .001; PFS: HR = 2.51, 95% CI [1.83,3.45]). Conclusions: The results of our analysis suggested that ctDNA is a potential biomarker that can be used to evaluate the prognosis of patients with ovarian cancer.
| S-EPMC8649094 | biostudies-literature