Utility of Alpha-Fetoprotein-L3 and Golgi Protein 73 for Diagnosis of Hepatocellular Carcinoma

2020 ◽  
Vol EJMM29 (4) ◽  
pp. 9-15
Author(s):  
Rania A. El-Kady ◽  
Mohammed M. El-Naggar ◽  
ehab A. Abd El-Shakour ◽  
Monir H. Bahgat

Background: Hepatocellular carcinoma (HCC) is amongst the most common malignant tumors that carries a poor prognosis. Clinically, alpha-fetoprotein (AFP) is the most extensively used serum biomarker for diagnosing HCC. Objectives: The current study was conducted to explore the diagnostic value of serum levels of alpha-fetoprotein-L3 (AFP-L3) and Golgi protein 73 (GP73) regarding HCC, and to determine the diagnostic accuracy of these biomarkers when used individually as well as in combination with AFP. Methodology: Blood samples were collected from 50 patients with HCV-related cirrhosis (25 subjects with HCC and 25 without HCC) recruited from the outpatient clinics of the Specialized Internal Medicine Hospital, Mansoura University, Egypt. Serum concentrations of AFP-L3 and GP73 were evaluated using enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of AFP-L3 and GP73 was determined by receiver operating characteristic (ROC) curve analysis. Results: Overall, the median serum level of AFP-L3 was higher in the HCC group compared to the cirrhotic group (p=0.05). Moreover, a statistically-significant difference was observed between the median serum value of GP73 in HCC patients compared to those with cirrhosis (p < 0.001). The ROC curve analysis showed that the area under the ROC curve (AUROC) values for AFP, AFP-L3 and GP73 were 0.88, 0.67 and 0.83, respectively. Of the 3 biomarkers, GP73 demonstrated the highest sensitivity (88%). The AUROC for AFP and AFP-L3 combination was 0.85, whereas that for AFP and GP73 was 0.90. Conclusion: Our findings indicate that GP73 is more sensitive than AFP and AFP-L3 in diagnosing HCC. Furthermore, the combined determination of GP73 and AFP could improve the diagnostic ability of HCC.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiajia Liu ◽  
Xiaoyi Tian ◽  
Yan Wang ◽  
Xixiong Kang ◽  
Wenqi Song

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.


2018 ◽  
Vol 33 (4) ◽  
pp. 439-446 ◽  
Author(s):  
Yunsheng Zhao ◽  
Lina Zhang ◽  
Lijing Huo ◽  
Liu Pei ◽  
Qiuping Li ◽  
...  

Objective: To investigate the clinical value of fucosylated GP73 (Fuc-GP73) levels for differential diagnosis of hepatocellular carcinoma from other liver diseases. Methods: Serum specimens were collected from 50 patients with hepatocellular carcinoma, 60 patients with other digestive system diseases (ODSD), and 40 normal controls. Lectin affinity chromatography column combining with the enzyme-linked immunosorbent assay (ELISA) using the ELISA index was utilized to measure the level of Fuc-GP73. By receiver operating characteristic (ROC) curve analysis its sensitivity and specificity were used to evaluate the diagnostic significance of Fuc-GP73 in hepatocellular carcinoma. Results: The median serum Fuc-GP73 level of hepatocellular carcinoma (20.4 μg/L) was much higher than that of ODSD patients (1.8 μg/L) and the normal controls group (0.3 μg/L), significantly ( P <0.01). There was no significant correlation between serum Fuc-GP73 level and sex, age, and tumor size in the hepatocellular carcinoma group ( P > 0.05); however, it was related to tumor, node, metastasis stage and lymph node metastasis ( P <0.05). The area under the ROC curve (AUC) of Fuc-GP73 to detect hepatocellular carcinoma alone was 0.885; with the prespecified specificity of 95%, the sensitivity and the cutoff value were 82% and 3.1 μg/L. In addition, the combined test of Fuc-GP73 with other biomarkers can improve the clinical diagnostic efficiency; the AUC can reach to 0.983; and with the prespecified specificity of 95% its sensitivity increased to 94%. Conclusion: Fuc-GP73 can act as a superior glycobiomarker for the differential diagnosis of hepatocellular carcinoma; its combined detection with other biomarkers can improve diagnostic accuracy.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Xin Wang ◽  
Ming-ming Li ◽  
Ye Niu ◽  
Xin Zhang ◽  
Ji-bin Yin ◽  
...  

Background. The gut microbiota is involved in the occurrence and development of chronic liver diseases. Zonulin is considered a marker of intestinal permeability. The purpose of this study was to assess zonulin levels in patients with chronic hepatitis B (CHB), HBV-associated liver cirrhosis (LC), and HBV-associated hepatocellular carcinoma (HCC). Materials and Methods. The study population consisted of 90 HBV-associated HCC patients, 90 HBV-associated LC patients, 90 CHB patients, and 90 healthy subjects. Serum levels of zonulin and AFP were determined. The diagnostic accuracy of each marker was evaluated using receiver operating characteristic (ROC) curve analysis (AUC). Results. Serum zonulin levels were significantly higher in patients with HCC than in patients with LC or CHB or healthy subjects (p<0.001). Moreover, the zonulin levels were increased in the advanced stage of LC and HCC. ROC curve analysis revealed that serum zonulin could be used to differentiate CHB from cirrhosis. In addition, the combination of zonulin and AFP exhibited a significantly larger AUC compared with zonulin or AFP alone. Conclusions. Serum zonulin levels were significantly increased both in LC and in HCC and correlated with the advanced stage of LC and HCC. Moreover, the combination of zonulin and AFP confers significant benefit to diagnostic accuracy in differentiating LC from HCC.


2020 ◽  
Vol 8 (1) ◽  
pp. 32
Author(s):  
Waseem A. Shoda

Background: Evaluation of diagnostic ability of preoperative estimation of serum thyroglobulin (TG) to detect malignant thyroid nodules (TN) in comparison to the American College of Radiology, Thyroid imaging reporting and data system (ACR-TIRADS), fine needle aspiration cytology (FNAC) and intraoperative frozen section (IO-FS).Methods: 34 patients with ACR-TIRADS 2-4 TN were evaluated preoperatively for identification of malignancy and all underwent total thyroidectomy with bilateral neck block dissection if indicated. Results of preoperative investigations were statistically analyzed using the Receiver operating characteristics (ROC) curve analysis as predictors for malignancy in comparison to postoperative paraffin sections.Results: Preoperative serum TG levels had 100% sensitivity and negative predictive value, while ACR-TIRADS scoring had 100% specificity and positive predictive value with accuracy rates of 95.35% and 97.67% for TG and TIRADS, respectively. ROC curve analysis defined preoperative ACR-TIRADS class and serum TG as highly diagnostic than FNAC for defining malignancy with non-significant difference between areas under curve for TIRADS and TG. For cases had intermediate risk of malignancy on TIRADS, IO-FS had missed 3, FNAC missed 4, while serum TG levels were very high in the 13 cases and were defined by ROC curve as the only significant predictor for malignancy.Conclusions: Preoperative estimation of serum TG showed higher diagnostic validity than FNAC, high predictability of cancer and ability to verify the intermediate findings on TIRADS. Combined preoperative TIRADS and TG estimation could accurately discriminate malignant TN with high accuracy and spare the need for preoperative FNAC or IO-FS. 


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S273-S273
Author(s):  
Amy C Sherman ◽  
Teresa C Smith ◽  
Daniel Espinoza ◽  
Yerun Zhu ◽  
Jessica Howard-Anderson ◽  
...  

Abstract Background Sensitive and specific SARS-CoV-2 antibody diagnostics are urgently needed to estimate the seroprevalence of SARS-CoV-2 infection in both the general population and special risk groups. Moreover, validated serologic assays are critical to understanding immunity to SARS-CoV-2 infection over time and identifying correlates of protection. Methods An enzyme-linked immunosorbent assay (ELISA) protocol to detect antibodies (IgG) that bind the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was validated and ROC curve analysis performed by testing a large panel of pre-pandemic sera (n=162) and convalescent sera from RT-PCR-confirmed COVID-19 cases (n=60). We then applied this test in two cohorts: 1) Healthcare personnel (HCP) that were enrolled in a longitudinal surveillance cohort just after peak local transmission and 2) Mildly ill patients being tested for SARS-CoV-2 infection by RT-PCR from NP swabs in an ambulatory testing clinic. Demographics of mildly symptomatic patients tested for SARS-CoV-2 with RT-PCR Results ROC curve analysis yielded an AUC of 0.9953, with a sensitivity and specificity at 91.67% and 99.38% at the optimal OD normalization threshold of 0.20. In 240 HCP surveilled at enrollment, 5.83% had positive IgG results. Of 19 symptomatic patients who presented to the ambulatory clinic, 5/19 had a positive PCR. In convalescence (13–74 days post symptom onset), 3 of those 5 were positive for IgG. Validation of the SARS-CoV-2 RBD ELISA ROC Curve Analysis Conclusion We demonstrated high sensitivity and specificity of the SARS-CoV-2 RBD ELISA. This simple assay is an efficient way to track seroconversion and duration of antibody responses to SARS-CoV-2 for different populations, particularly since RBD-binding antibodies have been shown to correlate with neutralization activity and may be useful to determine protective immunity following natural infection or vaccination. Ongoing work will assess variation in magnitude, character and duration of antibody responses in key populations and seek to maximize deployability of large-scale SARS-CoV-2 serology. Disclosures Jessica Howard-Anderson, MD, MSc, Antibacterial Resistance Leadership Group (ARLG) (Other Financial or Material Support, The ARLG fellowship provides salary support for ID fellowship and mentored research training) Nadine Rouphael, MD, Lilly (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Quidel (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)


2021 ◽  
Author(s):  
Wenqing Shi ◽  
Shinan Wu ◽  
Tie Sun ◽  
Huiye Shu ◽  
Qichen Yang ◽  
...  

Abstract Background: Gastric cancer (GC) is one of the most common malignancies in the population. Although the incidence of GC has reduced, patient prognosis remains poor. Ocular metastases (OM) from GC are rare, and the occurrence of OM is often indicative of severe disease. The purpose of this study was to explore the risk factors for OM of GC.Methods: A total of 1165 older adult patients with GC were enrolled in this study from June 2003 to May 2019 and divided into OM and non-ocular metastasis (NOM) groups. Chi-square and independent samples t tests were used to determine whether differences in demographic characteristics and serological indicators (SI) between the two groups were significant. In addition, binary logistic regression was used to analyze the value of various SI as risk factors for OM in patients with GC. The statistical threshold was set as P < 0.05. Finally, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of various SI in differentiating the occurrence of OM in patients with GC. Results: The incidence of OM in older adults with GC was 1.1%. Adenocarcinoma was the most common type of GC in both groups, and there was no significant difference in demographic characteristics, including sex and age between the groups. Low-density lipoprotein (LDL), carbohydrate antigen-724 (CA724), and carcinoembryonic antigen levels were significantly higher in the OM group than the NOM group, while those of apolipoprotein A1 (ApoA1) were significantly lower in the OM than the NOM group. Binary logistic analysis showed that LDL, ApoA1, and CA724 were independent risk factors for OM in patients with GC (P < 0.001,P = 0.033, and P = 0.008, respectively). ROC curve analysis generated area under the curve (AUC) values of 0.881, 0.576, and 0.906 for LDL, ApoA1, and CA724, respectively. In addition, combined analysis of LDL, ApoA1, and CA724 generated the highest AUC value of 0.924 (P < 0.001).Conclusion: Among SI, LDL, ApoA1, and CA724 have predictive value for the occurrence of OM in GC, with the three factors combined having the highest value.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Huandi Zhou ◽  
Le Jiang ◽  
Guohui Wang ◽  
Linlin Su ◽  
Liubing Hou ◽  
...  

Object. Hepatocellular carcinoma is one of the most common malignant tumors worldwide owing to its complicated molecular and cellular heterogeneity and its high incidence rate every year. It is an urgent need to search for new efficient molecular markers of HCC to reduce mortality and improve HCC prognosis. In this article, MCM4, a member of a family of proteins closely related to DNA replication and cell proliferation, was selected as a potential biomarker of HCC prognosis. Methods. MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort. Results. It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA ( AU C MCM 4 = 0.9461 , AU C AFP = 0.7056 ) and GEO (GSE19665: AU C MCM 4 = 0.8800 , AU C AFP = 0.5100 ; GSE64041 AU C MCM 4 = 0.8038 , AU C AFP = 0.6304 ). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC. Conclusion. MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.


2021 ◽  
pp. 1-7
Author(s):  
Meng-Lin Zhang ◽  
Wen-Juan Huang ◽  
Chen-Xi Yue ◽  
Ming-Ming Li ◽  
Na Li ◽  
...  

BACKGROUND: Platelets play a key role in tumor progression and metastasis. C-type lectin-like receptor 2 (CLEC-2) is the receptor expressed on platelets and the marker of platelet activation. OBJECTIVE: This study aims to determine whether soluble CLEC-2 levels differ between patients with benign colorectal polyps and those with colorectal cancer (CRC). METHODS: We measured plasma soluble CLEC-2 by enzyme-linked immunosorbent assay in 150 patients with colorectal polyps, 150 CRC patients without metastasis, 150 CRC liver metastasis, and 150 control subjects. RESULTS: The CRC patients had higher soluble CLEC-2 levels than patients with colorectal polyps (p< 0.001). Moreover, CRC patients with liver metastases displayed higher CLEC-2 levels than those in CRC patients without metastases (p< 0.001). In the CRC patients, CLEC-2 levels were correlated with lymph node metastasis and advanced stage. In the patients with polyps, there was a significant difference in CLEC-2 levels among patients with hyperplastic polyp, sessile serrated adenoma, and traditional serrated adenoma (p< 0.001). The ROC curve analysis revealed CLEC-2 had an optimal sensitivity of 77.3% and specificity of 94.6% for the screening of CRC, and sensitivity of 71.0% and specificity of 76.7% for the differential diagnosis of colorectal polyps and CRC. CONCLUSIONS: CRC patients have higher CLEC-2 levels than patients with colorectal polyps and healthy controls. Moreover, there is a significant difference in CLEC-2 levels among polyp subtypes. Further research is warranted.


2022 ◽  
Vol 21 ◽  
pp. 153303382110658
Author(s):  
Wen-Qing Shi ◽  
Shi-Nan Wu ◽  
Tie Sun ◽  
Hui-Ye Shu ◽  
Qi-Chen Yang ◽  
...  

Objective: The purpose of this study was to explore the risk factors for Ocular metastasis (OM) of Gastric cancer (GC). Methods: This is a retrospective cohort study. A total of 1165 patients with GC were enrolled in this study and divided into OM and non-ocular metastasis (NOM) groups. Chi-square and independent samples t tests were used to determine whether differences in demographic characteristics and serological indicators (SI) between the two groups were significant. In addition, binary logistic regression was used to analyze the value of various SI as risk factors for OM in patients with GC. The statistical threshold was set as P < .05. Finally, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of various SI in differentiating the occurrence of OM in patients with GC. Results: The incidence of OM in older adults with GC was 1.1%. Adenocarcinoma was the most common type of GC in both groups, and there was no significant difference in demographic characteristics between the groups. Low-density lipoprotein (LDL), carbohydrate antigen-724 (CA724), and carcinoembryonic antigen levels were significantly higher in the OM group than the NOM group, while those of apolipoprotein A1 (ApoA1) were significantly lower in the OM than the NOM group. Binary logistic analysis showed that LDL, ApoA1, and CA724 were independent risk factors for OM in patients with GC ( P < .001, P = .033, and P = .008, respectively). ROC curve analysis generated area under the curve (AUC) values of 0.881, 0.576, and 0.906 for LDL, ApoA1, and CA724, respectively. In addition, combined analysis of LDL, ApoA1, and CA724 generated the highest AUC value of 0.924 ( P < .001). Conclusion: Among SI, LDL, ApoA1, and CA724 have predictive value for the occurrence of OM in GC, with the three factors combined having the highest value.


2019 ◽  
Author(s):  
Jing Li ◽  
Min Ming ◽  
Yonghong Han

Abstract Background This study aimed to investigate the predictive value of JNK pathway-associated phosphatase (JKAP) level for severe acute pancreatitis (SAP) risk, and its association with disease severity, inflammation and in-hospital mortality in SAP patients. Methods Our study recruited 50 SAP patients, 50 moderate-severe acute pancreatitis (MSAP) patients, 50 mild acute pancreatitis (MAP) patients and 50 healthy controls. And the serum samples were obtained from all acute pancreatitis patients within 24 hours after admission and from health controls at their enrollment to detect JKAP level by enzyme-linked immunosorbent assay. Results JKAP level was decreased in SAP patients compared with healthy controls, MSAP and MAP patients. And receiver operating characteristics (ROC) curve analysis revealed that JKAP could not only distinguish SAP patients from healthy controls (AUC: 0.914, 95%CI: 0.857-0.971), but also differentiate SAP patients from MAP patients (AUC: 0.869, 95%CI: 0.802-0.937) and MSAP patients (AUC: 0.712, 95%CI: 0.610-0.813). In SAP patients, JKAP was negatively correlated with Ranson score, acute physiology and chronic health care evaluation II (APACEH II) score, sequential organ failure assessment (SOFA) score and C-reactive protein (CRP). And lower JKAP level, higher CRP level, Ranson score, APACEH II score and SOFA score were associated with increased in-hospital mortality in SAP patients. Additionally, ROC curve analysis showed that JKAP could predict decreased in-hospital mortality in SAP patients (AUC: 0.720, 95%CI: 0.526-0.914). Conclusions JKAP might serve as a biomarker for disease risk and management for SAP.


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