Pleomorphic adenoma gene 1 expression is associated with the diagnosis of hepatocellular carcinoma

2020 ◽  
Author(s):  
Xianfeng Zhang ◽  
Xianjun Zhang ◽  
Xinguo Li ◽  
Hongbing Bao ◽  
Guang Li ◽  
...  

Abstract Background: The pleomorphic adenoma gene 1 (PLAG1)) has been reported to be overexpressed in pleomorphic adenoma (PA). However, its expression and clinical significance in hepatocellular carcinoma (HCC) has not been investigated.Methods: PLAG1 protein levels in HCC serum and benign liver diseases (BLD) controls were measured by Western Blot, and α-fetoprotein (AFP) concentration was analyzed by enzyme-linked immunosorbent assay (ELISA). The relevance of PLAG1expression with the clinicopathological factors was assessed by Chi-square test. Furthermore, the receiver operating characteristic (ROC) curve was performed to investigate the values of the markers in diagnosis of HCC.Results: Serum PLAG1 protein level was significantly elevated in HCC group compared to that in controls (P<0.001). Furthermore, a significant association was found between PLAG1 expression and clinical factors, such as tumor size (P=0.000), differentiation (P=0.014) and metastasis (P=0.001). ROC analysis showed that PLAG1 could distinguish HCC patients from BLD controls with the area under the ROC curve (AUC) of 0.852 (95 % CI: 0.782-0.922; 78.8% sensitivity, 83.3% specificity; P<0.001), which had significantly superior discriminative ability than AFP (AUC=0.694, 67.3% sensitivity and 62.1 % specificity) or the combination of PLAG1 and AFP (AUC=0.706, 69.2% sensitivity and 63.6 % specificity).Conclusions: This study suggested that serum PLAG1 might be a potential noninvasive tumor biomarker in the diagnosis of HCC.

2020 ◽  
Author(s):  
Zhong Dai ◽  
Ke-Qing Yao ◽  
Xing-Sheng Hu ◽  
Yi-Qun Li ◽  
Yu-Tao Liu ◽  
...  

Abstract Background: Sperm-associated antigen 9 (SPAG9) has been proposed as a novel biomarker for early diagnosis of human tumors. This study was aimed to assess the clinical value of serum SPAG9 for HCC diagnosis.Methods: Serum SPAG9 was measured by quantitative real-time ploymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Chi-square test was applied to evaluate the association between serum SPAG9 mRNA level and clinical characteristics. The diagnostic accuracy of the serum SPAG9 mRNA was assessed using receiver operating characteristic (ROC) curve.Results: Serum SPAG9 level was significantly higher in HCC patients than that in healthy controls at both mRNA and protein levels (P<0.01 for all). Furthermore, serum SPAG9 mRNA level was positively correlated with TNM stage (P=0.047), tumor size (P=0.044), and lymph node metastasis (P=0.014). The area under the curve (AUC) of the ROC curve was 0.794, with a sensitivity of 71.4%, a specificity of 80.4%, suggesting the high diagnostic accuracy of serum SPAG9 mRNA for HCC. The cutoff value was 1.030.Conclusions: Serum SPAG9 is significantly increased in HCC, and positively correlated with aggressive clinical characteristics. SPAG9 may serve as a diagnostic biomarker for HCC.


2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 91-91 ◽  
Author(s):  
David James Pinato ◽  
Francesco A Mauri ◽  
Paolo Spina ◽  
Owen Cain ◽  
Abdul Siddique ◽  
...  

91 Background: Programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) enriches for responses to PD-1/PD-L1 inhibitors, however its role as a predictive biomarker in hepatocellular carcinoma (HCC) is inconclusive, with no consensus on any particular assay. We evaluated the performance of 4 different PD-L1 detection assays previously published in landmark clinical studies. Methods: PD-L1 IHC was performed on 4 serial sections from tissue microarray (TMA) blocks containing 100 archival cases of HCC that included tumour and surrounding non-tumorous tissue. Antibody clones E1LN3, 28-8, 22c3, SP263 were compared on the basis of percentage and intensity of staining in malignant cells (M) to generate an H-score (range 0-300). Immune cells infiltrating (ICI) and at the periphery, in non-tumorous tissue (ICP) were scored on a 4-tier system (0-3). Results: Patients were 76% males, 20% HCV-positive, 64% cirrhotic with a median age of 67 years. Median tumour size was 4 cm, 70% of patients had T1-T2 tumours and 48% were of grade 2. The proportion of PD-L1 positive cases according to M-ICI-ICP pattern was 2-6-2% for E1LN3, 10-18-19% for 28-8, 9-22-18% for 22c3 and 5-14-13% for SP263. Pairwise comparison of M H-scores revealed heterogeneity across antibodies, with highest concordance between E1L3N/SP263 (R2 = 0.95), E1L3N/22c3 (R2 = 0.65), 22c3/SP263 (R2 = 0.66) and increasing discordance for 28-8/22c3 (R2 = 0.44), E1L3N/28-8 (R2 = 0.29), and 28-8/SP263 (R2 = 0.26). Detection of PD-L1-positive immune infiltrates using a semi-quantitative scoring system revealed significantly different scores in pairwise non-parametric comparisons of ICI (p < 0.05) but not ICP (p > 0.05 for chi-square test). Conclusions: In the Blueprint-HCC study we demonstrated that quantification of PD-L1 protein levels in tumour cells, intra-tumoural and peri-tumoural infiltrate is characterised by inter-assay discordance in HCC. This has profound implications in the clinical development of predictive correlates of efficacy to immunotherapy in HCC. Sources of such discordance should be explored.


2020 ◽  
Author(s):  
Xianfeng Zhang ◽  
Xianjun Zhang ◽  
Xinguo Li ◽  
Hongbing Bao ◽  
Guang Li ◽  
...  

Abstract Background: This study was designed to investigate the serum level of HIV-1 Tat interactive protein 2 (HTATIP2) mRNA in hepatocellular carcinoma (HCC) patients and its diagnostic significance in the disease.Methods: The serum HTATIP2 mRNA level was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between HTATIP2 expression and clinical parameters was analyzed using Chi-square test. Receiver operating characteristics (ROC) curve was adopted to estimate the diagnostic role of serum HTATIP2 in HCC.Results: HCC patients showed a significantly lower serum level of HTATIP2 than the healthy control (P<0.001). The level of HTATIP2 was closely associated with venous invasion (P=0.011), lymph node metastasis (P=0.007) and TNM stage (P=0.016). ROC curve demonstrated that HTATIP2 could discriminate between HCC patients and healthy individuals at the optimal cutoff point of 2.39. Besides, the AUC was 0.892, with the corresponding sensitivity and specificity of 83.90% and 84.37%, respectively. Conclusions: HTATIP2 is negatively expressed in HCC and may be a diagnostic biomarker for this disease.


2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.


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.


2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  

Abstract Background Cholangiocarcinoma (CCA) is one of the most aggressive malignancies. Late diagnosis may be responsible for the high mortality. MicroRNA-106b (MiR-106b) is accepted as an important regulator in various human malignancies. The current study was aimed to investigate the diagnostic value of miR-106b in CCA. Methods Serum levels of miR-106b in CCA patients and healthy control were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was used to analyze the association of miR-106b with the clinicopathological features. To evaluate the diagnostic value of miR-106b in CCA, the ROC curve was constructed. Results The expression of miR-106b was significantly increased in CCA samples compared with the healthy controls (P < 0.001). The overexpression of miR-106b was remarkable correlated with the lymphatic node metastasis (P = 0.038), clinical stage (P = 0.017) and differentiation (P = 0.009). ROC curve suggested that miR-106b was an effective diagnostic biomarker in CCA with the AUC of 0.913. The optimal cutoff value was 2.525, with the sensitivity of 89.7% and the specificity of 79.3%. Conclusions MiR-106b functions as an oncogene in CCA, which may be an potential diagnostic biomarker for CCA.


2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Junjie Jiang ◽  
Hui-Ju Wang ◽  
Xiao-Zhou Mou ◽  
Huanqing Zhang ◽  
YiZhen Chen ◽  
...  

Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC. Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly. Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues. Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.


2021 ◽  
Author(s):  
Siqi Xu ◽  
hongsheng Li ◽  
xiaoyan Wu ◽  
jianwei Guo ◽  
jiaoli Zhang ◽  
...  

Abstract ObjectiveThis study aimed to evaluate the necessity of Western blotting (WB) in samples with inconsistent results in detecting anti-treponema pallidum (TP) antibodies by enzyme-linked immunosorbent assay (ELISA) and Treponema pallidum granule agglutination assay (TPPA). MethodsSpecific anti-TP test results in our clinical laboratory were retrospectively analyzed. The specimens with a positive or a negative result, but with colored ELISA plates, were retested by TPPA. WB was used to confirm the suspicious results between ELISA and TPPA. The chi-square test was used to analyze whether the difference was statistically significant. ResultsA total of 106,757 anti-TP specimens were screened by ELISA from August 2018 to December 2019; 3972 were retested by TPPA, and 3809 were positive by TPPA. ELISA and TPPA showed different results in 163 specimens. Among them, 29 specimens were negative and 134 were positive by ELISA; 76 were negative, 23 were positive, and 64 were “reserve” by TPPA; 93 were negative, 31 were positive, and 39 were suspicious by the WB confirmation test. Compared with WB, the difference in the results of ELISA and TPPA was statistically significant. ConclusionsTPPA is an effective retest method for anti-TP antibody detection. If the results of anti-TP antibodies by ELISA and TPPA are inconsistent, it is necessary to use WB for confirmation.


2021 ◽  
Author(s):  
Cai Xin ◽  
Tang Dongling ◽  
Chen Juanjuan ◽  
Li Huan ◽  
Hu Yuanhui ◽  
...  

Abstract Background There is an urgent need for new serum biomarkers for early screening of HBV-related hepatocellular carcinoma (HCC). Fibrinogen like protein 1 (FGL1) may develop the potential diagnostic value of alpha fetoprotein (AFP) in HBV-related HCC. Methods The TCGA database was used to screen out genes related to liver cancer and perform differential expression analysis. Enzyme-linked immunosorbent assay and chemiluminescence immunoassay were used to detect concentrations of FGL1 and AFP. Using immunofluorescence semi-quantitative method to detect the mean fluorescence intensity of FGL1. Result FGL1 is lower in tumor tissues than in normal tissues. The serum levels of FGL1 and AFP in patients with HBV-related HCC are significantly higher than others for each group. Compared with other groups, the area under the receiver operating curve (AUC) of FGL1 is higher than that of AFP when compared with the normal group, and the AUC of other groups is lower than that of AFP. The combination of the two can increase the AUC to 0.862 (95%CI, 0.786 ~ 0.918) in distinguishing benign liver disease from HBV-related HCC. The specificity of FGL1 and AFP in the diagnosis of HBV-related HCC is 98.39% and 70.97%, respectively. The specificity of the combination was 93.55%. In distinguishing the A and B stages in the BCLC staging, the combination of the two increased the AUC from 0.584 to 0.647. When distinguishing benign liver disease from HBV-related HCC, the AUC of FGL1 reached 0.849, with a specificity of 100%. Conclusion FGL1 can be used as a non-invasive biomarker for HCC. When combined with AFP, the diagnostic efficiency and specificity were improved.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 289-289
Author(s):  
Kit Man Wong ◽  
Jonghun John Lee ◽  
Amy Wong ◽  
Geoffrey Liu ◽  
Morris Sherman ◽  
...  

289 Background: Studies have demonstrated clinical differences in hepatocellular carcinoma (HCC) between Asians (AS) and non-Asians (NAS). In the US, AS are less likely to undergo liver transplant compared to Caucasians. Despite the large immigrant population in Canada, there has been no prior comparison of HCC in AS and NAS in the context of the Canadian universal health care system. We retrospectively evaluated the ethnic differences in HCC at the largest cancer centre in Canada. Methods: We analyzed 268 patients who enrolled in a Genetic Epidemiology Study of HCC (April 2010 to February 2013), where patients were asked to complete a questionnaire and give a blood sample at their first visit. Relevant clinical data were extracted and analyzed by descriptive statistics, t-test or Chi-square test. Results: The study population had a mean age of 61 years and 83% males. There were 45% AS, 49% Caucasians, and 6% other ethnicities. Etiologies of HCC included: Hepatitis B (HBV) 34%, Hepatitis C (HCV) 32%, non-alcoholic steatohepatitis 15%, alcohol 18%. Compared to NAS, HCC patients of Asian ancestry had significantly higher rates of HBV (60% vs. 12%, p<0.001). At diagnosis, 83% of patients were Child-Pugh A (mean MELD score 9.2). Ethnicity had no impact on Child-Pugh class, multifocal disease or macrovascular invasion. However, MELD scores were lower in AS (p=0.02). Overall, 71% of cases were initially treated with curative intent. Patients underwent various treatment modalities: liver transplant 13%, resection 31%, radiofrequency ablation 39%, transarterial chemoembolization (TACE) 21%, radiation 17%, systemic therapy 27%. AS had higher resection rates (41% vs. 22%, p<0.001), while no differences were observed for other treatments. Duration of response was 11.7 months for TACE (AS 14.2, NAS 10.5), 7.5 months for sorafenib (AS 6.8, NAS 8.1). Rate of intolerance to sorafenib was 24% (AS 27%, NAS 22%, p=0.63). This analysis was limited by inherent bias in the selection of study patients. Conclusions: AS with HCC tend to have HBV and lower MELD scores, and to undergo resection in a public health care setting with no differences in the uptake of other therapies. An analysis of survival based on ethnicity will be reported.


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