scholarly journals Clinical Relevance of Soluble Forms of Immune Checkpoint Molecules sPD-1, sPD-L1, and sCTLA-4 in the Diagnosis and Prognosis of Ovarian Cancer

Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 189
Author(s):  
Janina Świderska ◽  
Mateusz Kozłowski ◽  
Katarzyna Nowak ◽  
Małgorzata Rychlicka ◽  
Dorota Branecka-Woźniak ◽  
...  

It is crucial to find new diagnostic and prognostic biomarkers. A total of 80 patients were enrolled in the study. The study group consisted of 37 patients with epithelial ovarian cancer, and the control group consisted of 43 patients with benign ovarian cystic lesions. Three proteins involved in the immune response were studied: PD-1, PD-L1, and CTLA-4. The study material was serum and peritoneal fluid. The ROC curve was plotted, and the area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The cut-off level of CTLA-4 was 0.595 pg/mL, with the sensitivity and specificity of 70.3% and 90.7% (p = 0.000004). Unfavorable prognostic factors determined in serum were: PD-L1 (for PFS: HR 1.18, 95% CI 1.11–1.21, p = 0.016; for OS: HR 1.17, 95% CI 1.14–1.19, p = 0.048) and PD-1 (for PFS: HR 1.01, 95% CI 0.91–1.06, p = 0.035). Unfavorable prognostic factors determined in peritoneal fluid were: PD-L1 (for PFS: HR 1.08, 95% CI 1.01–1.11, p = 0.049; for OS: HR 1.14, 95% CI 1.10–1.17, p = 0.045) and PD-1 (for PFS: HR 1.21, 95% CI 1.19–1.26, p = 0.044). We conclude that CTLA-4 should be considered as a potential biomarker in the diagnosis of ovarian cancer. PD-L1 and PD-1 concentrations are unfavorable prognostic factors for ovarian cancer.

2020 ◽  
Author(s):  
Zhi-Cheng Liu ◽  
Yan-Qing Li ◽  
Yan Jiao ◽  
Yue-Chen Zhao

Abstract Background: Liver cancer (LC) is a common malignancy with very high morbidity. Pyruvate dehydrogenase kinases (PDKs) are regulators of mitochondrial pyruvate dehydrogenase complexes (PDCs) and play an important role in regulating cellular energy metabolism. In this study, The Cancer Genome Atlas (TCGA) database was used to analyze the expression of PDK2 mRNA in LC, and to explore the value of PDK2 in the diagnosis and prognosis of LC.Methods: The TCGA database, containing the clinical data of 373 LC patients, includes information on PDK2 expression values. The receiver operating characteristic (ROC) curve of PDK2 was drawn to evaluate its diagnostic ability. Patients were divided into PDK2 high- and low-expressing groups by threshold levels. The Chi-square test was used to evaluate the correlation between PDK2 levels and clinicopathological characteristics. The Kaplan-Meier estimator and Cox regression analysis were performed to assess the effect of PDK2 levels on survival outcomes.Results: PDK2 expression in LC tissue was lower than that in normal liver tissues. According to the area under the curve (AUC) value calculated by ROC, PDK2 has a considerable diagnostic value for LC prognosis. The decreased expression of PDK2 is associated with clinical parameters, such as histologic grade ( P =0.0001), radiation therapy ( P =0.0490), vital status ( P =0.0240), and overall survival (OS) ( P =0.0222). Multivariate analysis shows that decreased PDK2 level is an independent risk factor for predicting poor prognosis in LC.Conclusions: PDK2 has a significant impact on the prognosis of LC and is a potential biomarker for the diagnosis and prognosis of LC.


2021 ◽  
Vol 10 (14) ◽  
pp. 3058
Author(s):  
Aleksandra Mielczarek-Palacz ◽  
Celina Kruszniewska-Rajs ◽  
Marta Smycz-Kubańska ◽  
Jarosław Strzelczyk ◽  
Wojciech Szanecki ◽  
...  

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.


2010 ◽  
Vol 2 ◽  
pp. BIC.S6040 ◽  
Author(s):  
Yulia A. Savitskaya ◽  
Genaro Rico ◽  
Luis Linares ◽  
Roberto González ◽  
René Téllez ◽  
...  

Background Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis. Objectives To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers. Methods Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)–IgM directly in the peripheral blood sera of humans. Results Serum ANG–IgM levels are significantly higher in osteosarcoma patients than in healthy individuals ( P < 0.005). Serum ANG–IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG–IgM in the sera of 85% of newly diagnosed osteosarcoma patients and ANG–IgM levels were significantly higher in osteosarcoma patients compared to any other tumors ( P < 0.001). Conclusions These results demonstrated that the combined biomarker ANG–IgM has greater sensitivity and specificity in early diagnosis of osteosarcoma patients than the traditional biomarkers (ANG and vascular endothelial growth factor). Circulating ANG–IgM immune complexes can potentially serve as a biomarker for increased risk of osteosarcoma, because relatively high serum levels were also detected in otherwise healthy individuals with a first degree family history of osteosarcoma and in patients with a diagnosis of benign conditions. Immunological aspects of angiogenesis for managing osteosarcoma will have a practical value in early diagnosis, prognosis and monitoring response to antiangiogenic therapy.


2018 ◽  
Author(s):  
Shoufeng Zhao ◽  
Zhipeng Wang

ABSTRACTOvarian cancer (OC) is commonly diagnosed at an advanced stage due to a lack of effective biomarkers and specificity required for accurate clinical diagnosis. The purpose of this study was to estimate the diagnosis and prognosis of the NaPi- II b in ovarian cancer. Herein, by performing data mining using the databases of Oncomine and Cancer Cell Line Encyclopedia (CCLE), we are for the first time to report that the expression level of NaPi- II b transcripts in a variety of tumor types compared with the normal controls. Based on Kaplan-Meier plotter, we investigated the prognostic values of NaPi- II b specifically high expressed in OC patients. The results of the Oncomine analysis showed that relative expression of NaPi- II b was distinctly high in OC tissues vs. normal tissues. CCLE analysis indicated that the expression of NaPi- II b in OC cell lines expressed the highest level in all cancer lines. In overall survival (OR) analysis, NaPi- II b mRNA high expressions were correlated to worse OR in OC patients. These results indicate that NaPi- II b may be a novel potential biomarker for determining the diagnosis and predicting the prognosis of OC.


2016 ◽  
Vol 40 (3-4) ◽  
pp. 707-715 ◽  
Author(s):  
Ruyi Huang ◽  
Xiaochen Wang ◽  
Wenjie Zhang ◽  
Guangyan Zhangyuan ◽  
Kangpeng Jin ◽  
...  

Background/Aims: Long non-coding RNAs (lncRNAs) have been reported to play pivotal roles in multiple tumors and can act as tumor biomarkers. In this study, we explored the association of the expression of an lncRNA, DGCR5 with clinicopathological features and prognosis in HCC. Methods: Expression levels of DGCR5 were detected by quantitative real-time PCR (qRT-PCR) and the clinical data was obtained, including basic information, data of clinicopathology and cancer specific survival rate. Receiver operating characteristic (ROC) curve, Kaplan-Meier methods and multivariable Cox regression models were used to analyze predictive efficiency, long-term survival outcomes and risk factors. Results: DGCR5 was found down-regulated in HCC tissues (P<0.001) and serum (P = 0.0035) and low expression of DGCR5 was correlated with a poor cancer specific survival (CSS) (P = 0.0019), as the overall 5-year CSS rates were 10.3% (low expression group) and 36.6% (high expression group), respectively. A stratified analysis demonstrated that low DGCR5 expression was an independent negative prognostic factor for HCC. In addition, the area under the ROC curve was 0.782 with a sensitivity of 0.633 and a specificity of 0.833. Conclusions: Our results suggest that DGCR5 may be a participator in HCC and can serve as potential biomarker for the diagnosis and prognosis in HCC.


2004 ◽  
Vol 22 (4) ◽  
pp. 678-685 ◽  
Author(s):  
Andreas Scorilas ◽  
Carla A. Borgoño ◽  
Nadia Harbeck ◽  
Julia Dorn ◽  
Barbara Schmalfeldt ◽  
...  

PurposeHuman kallikrein 13 (hK13; encoded by the KLK13 gene) is a secreted serine protease expressed in endocrine tissues, including the prostate, testis, breast, and ovary. We have previously reported steroid hormone regulation of the KLK13 gene and its clinical value as a marker of favorable prognosis in breast cancer at the mRNA level. We hypothesized that hK13 may represent a potential biomarker for ovarian carcinomas.Patients and MethodsUsing a newly developed enzyme-linked immunosorbent assay (ELISA), hK13 levels were quantified in 131 ovarian tumor extracts and correlated with various clinicopathological variables and outcome (progression-free survival [PFS], overall survival [OS]), over a median follow-up period of 42 months.ResultshK13 concentration in ovarian tumor cytosols ranged from 0 to 18.4 ng/mg of total protein. An optimal cutoff value of 0.13 ng/mg (67thpercentile) was selected, based on the ability of hK13 values to predict the PFS of the study population, to categorize tumors as hK13-positive or negative. Women with hK13-positive tumors most often had early stage (stage I/II) disease, no residual tumor after surgery and optimal debulking success (P < .05). Univariate and multivariate Cox regression analyses revealed that patients with hK13-positive tumors had a significantly longer PFS and OS than hK13-negative patients (P < .05). Kaplan-Meier survival curves further confirmed a reduced risk of relapse and death in women with hK13-positive tumors (P = .007 and P = .002, respectively).ConclusionThese results indicate that hK13 is an independent marker of favorable prognosis in ovarian cancer.


2020 ◽  
Author(s):  
Nan Zhang ◽  
Zhiyou Yang ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Jiani Yang ◽  
...  

Abstract Background Ovarian cancer remains one of the most lethal malignancies in women which is typically diagnosed at a late stage and has no effective screening strategy. It is essential to explore novel biomarkers for the diagnosis and prognosis of ovarian cancer, as well as therapeutic targets. Recent studies have shown that circRNAs participate in ovarian cancer progression by regulating various processes and being able to act as potential biomarkers for ovarian cancer diagnosis and prognosis. In the present study we aimed to explore the prognostic role of circ_0078607 in high-grade serous ovarian cancer. Results The expression of circ_0078607 in 49 high-grade serous ovarian cancer and adjacent non-cancerous tissue samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We noticed that circ_0078607 expression was significantly downregulated in ovarian cancer tissues compared with adjacent non-cancerous tissues. Besides, patients with low circ_0078607 expression exhibited parameters associated with poor prognosis, including advanced FIGO stage and higher serum CA125 level. Kaplan-Meier survival curve analysis showed that both progression-free survival and overall survival were significantly shortened in patients with low circ_0078607 expression. Cox regression model analysis showed that low expression of circ_0078607 was an adverse prognostic indicator for high-grade serous ovarian cancer patients. Conclusions Low expression of circ_0078607 might be an adverse prognostic indicator for high-grade serous ovarian cancer patients.


Author(s):  
Arsalan Majeed Adam ◽  
Muhammad Armughan Ali ◽  
Arshad Ali Shah ◽  
Ather Hasan Rizvi ◽  
Aiman Rehan ◽  
...  

Background: The diagnosis and management of acute coronary syndrome (ACS) have improved significantly over the past few decades; however, the recognition of myocardial ischemia still proves to be a dilemma for cardiologists. The aim of this study was to determine the role of hematological and coagulation parameters in the diagnosis and prognosis of patients with ACS. Methods: This prospective study recruited 250 patients with ACS and 250 healthy controls. The diagnostic role of hematological and coagulation parameters was assessed by comparing the patients with ACS with the control group. The relationships between these parameters and mortality were determined by dividing the patients into 2 groups: Group A (discharged) and Group B (patients who died within 30 days of follow-up). Multivariate Cox regression analysis was performed to calculate the hazard ratio (HR). Results: The mean age of the patients was 55.14±10.71 years, and 65.2% of them were male.  Prothrombin time (P<0.001), activated partial thromboplastin time (P<0.001), mean platelet volume (MPV) (P<0.001), white blood cell (WBC) count (P<0.001), and red blood cell distribution width (RDW) (P<0.001) were significantly higher in the case group than in the control group. WBC count (P<0.001), RDW (P<0.001), and MPV (P<0.001) were significantly higher in the controls than in the case group. The Cox regression model showed that RDW above 16.55% (HR=6.8), MPV greater than 11.25 fL (HR=2.6), and WBC higher than 10.55×103/μL (HR=6.3) were the independent predictors of mortality. Conclusion: In addition to being the independent predictors of short-term mortality, RDW, WBC, and MPV when used together with the coagulation profile may aid in the diagnosis of ACS in patients presenting with chest pain.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1080
Author(s):  
Radu-Stefan Miftode ◽  
Daniela Constantinescu ◽  
Corina Maria Cianga ◽  
Antoniu Octavian Petris ◽  
Amalia-Stefana Timpau ◽  
...  

Background: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians’ interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value. Methods: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach. Results: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 (r(120) = 0.20, p < 0.002). Conclusions: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF.


2012 ◽  
Vol 22 (7) ◽  
pp. 1106-1112 ◽  
Author(s):  
Li Wu ◽  
Zhi-Yuan Dai ◽  
Yong-Hong Qian ◽  
Yan Shi ◽  
Feng-Ju Liu ◽  
...  

ObjectiveHuman epididymis protein 4 (HE4), a precursor of human epididymis protein, has been recently identified as a new promising serum biomarker for ovarian carcinoma. We performed a systematic review of studies that investigated the use of HE4 in the diagnosis of ovarian cancer in patients with pelvic or gynecological masses. We also evaluated the diagnostic performance of HE4 for differentiating between patients with benign gynecological disease and those with ovarian cancer.MethodsWe searched PubMed database (1990–2011) to collect articles in English that evaluated the diagnostic value of HE4 in patients with gynecological or pelvic masses. Two reviewers independently assessed the methodological quality of each study using the quality assessment of diagnostic accuracy studies tool. The data were analyzed using Meta-Disc1.4 software. Meta-analysis of the reported sensitivity and specificity of each study and summary receiver operating characteristic (SROC) curve were performed.ResultsA total of 9 studies involving 1807 women were included. When the control group was composed of healthy women, the pooled sensitivity and specificity for HE4 in diagnosing ovarian cancer were 83% (95% confidence interval [CI], 77%–88%) and 90% (95% CI, 87%–92%), respectively. The area under the SROC curve was 0.9271. When the control group was composed of women with benign disease, the pooled sensitivity and specificity for HE4 were 74% (95% CI, 69%–78%) and 90% (95% CI, 87%–92%). The area under the SROC curve was 0.8853.ConclusionThe current analysis indicated that HE4 may be a valuable marker in the diagnosis of ovarian carcinoma. Serum HE4 detection is not only a useful preoperative test for predicting the benign or malignant nature of pelvic masses but has a potential to be used as an initial step in ovarian cancer screening strategy.


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