Quantitative comparison of PD-L1 immuno-histochemical assays in hepatocellular carcinoma: The Blueprint-HCC study.

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.

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

10.21203/rs.3.rs-28761/v1 ◽

2020 ◽

Author(s):

Xianfeng Zhang ◽

Xianjun Zhang ◽

Xinguo Li ◽

Hongbing Bao ◽

Guang Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Pleomorphic Adenoma ◽

Roc Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Tumor Biomarker ◽

Chi Square ◽

Discriminative Ability ◽

Protein Levels ◽

Chi Square Test ◽

Benign Liver

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.

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Prognostic Significance of NBEAL2 in Liver hepatocellular carcinoma

10.21203/rs.3.rs-471663/v1 ◽

2021 ◽

Author(s):

Yanghui Wen ◽

Hui Su ◽

Wuke Wang ◽

Feng Ren ◽

Haitao Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Expression Profiles ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Clinicopathological Parameters ◽

Chi Square ◽

Kaplan Meier ◽

Chi Square Test ◽

Liver Hepatocellular Carcinoma ◽

The Relationship

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.

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RELATION OF GRADES OF HYPONATREMIA ON SEVERITY OF BRONCHIOLITIS

International Journal of Medical Science and Diagnosis Research ◽

10.32553/ijmsdr.v5i3.774 ◽

2021 ◽

Vol 5 (3) ◽

Author(s):

Nirmal Georgie Ninan ◽

Sanjeev Kumar TM

Keyword(s):

Bacterial Infections ◽

Severe Disease ◽

Pairwise Comparison ◽

Cross Sectional Study ◽

Significant Relation ◽

Electrolyte Abnormality ◽

Chi Square ◽

Cross Sectional ◽

Chronic Disorder ◽

Chi Square Test

Background and objectives: Hyponatremia often occurs among children with bronchiolitis. It is the most common electrolyte abnormality associated with severe disease course. Aim was to study relation between sodium levels and severity of bronchiolitis Methodology: Cross-sectional study was conducted on 72 infants admitted with bronchiolitis to Pediatrics ward/ICU, JMMC. Infants with recurrent respiratory or super added bacterial infections, born <34weeks gestation, any chronic disorder or medications that can influence electrolyte levels or parents unwilling for consent were excluded. Severity of bronchiolitis was scored and classified into mild, moderate, severe. Sodium levels were determined and grouped (in mmol/L) into normonatremia (135-145) and hyponatremia (mild (130-134), moderate (125-129) and severe (≤124). The grade of hyponatremia with severity of bronchiolitis was compared. Chi square test was used to test the association of severity of bronchiolitis and category of hyponatremia. ANOVA test was done to compare the severity of bronchiolitis with sodium levels. Results: Hyponatremia was seen in 50% of cases admitted with severe bronchiolitis, which when compared to mild and moderate bronchiolitis, was statistically significant (p<0.001). ANOVA showed mean sodium levels of mild, moderate and severe bronchiolitis were 138.44±1.81, 137.37±1.76 and 135.43±3.93 respectively; these were statistically significant (p<0.001). A pairwise comparison between mild and moderate bronchiolitis with hyponatremia was not found to be statistically significant (p-0.769) but comparison between mild and severe bronchiolitis with hyponatremia was statistically significant (p<0.001) Conclusion: There is statistically significant relation between hyponatremia and severity of bronchiolitis. Hyponatremia could be considered as a marker to assess the severity of bronchiolitis. Keywords: Bronchiolitis, Hyponatremia, Respiratory distress

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Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/15330338211033063 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110330

Author(s):

Junjie Jiang ◽

Hui-Ju Wang ◽

Xiao-Zhou Mou ◽

Huanqing Zhang ◽

YiZhen Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Normal Liver ◽

Clinicopathological Parameters ◽

Expression Array ◽

Chi Square ◽

Normal Tissues ◽

Kaplan Meier ◽

Chi Square Test ◽

The Relationship ◽

Liver Tissues

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.

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Differences in clinical characteristics and treatment in hepatocellular carcinoma between Asians and non-Asians.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.289 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 289-289

Author(s):

Kit Man Wong ◽

Jonghun John Lee ◽

Amy Wong ◽

Geoffrey Liu ◽

Morris Sherman ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Health Care ◽

Liver Transplant ◽

Meld Score ◽

Public Health Care ◽

Treatment Modalities ◽

Chi Square ◽

Curative Intent ◽

Chi Square Test ◽

Multifocal Disease

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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Sperm-Associated Antigen 9 Assumes Signifying Capacity in Hepatocellular Carcinoma Diagnosis

10.21203/rs.3.rs-52891/v1 ◽

2020 ◽

Author(s):

Zhong Dai ◽

Ke-Qing Yao ◽

Xing-Sheng Hu ◽

Yi-Qun Li ◽

Yu-Tao Liu ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Roc Curve ◽

Clinical Characteristics ◽

Mrna Level ◽

Area Under The Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Clinical Value ◽

Chi Square ◽

Protein Levels ◽

Chi Square Test

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.

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Gene Polymorphism of MUC15, MMP14, BRAF, and COL1A1 Is Associated with Capsule Formation in Hepatocellular Carcinoma

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2021/9990305 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Wei Sun ◽

Yongchao Zhang ◽

Bozhi Liu ◽

Youjia Duan ◽

Wei Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Logistic Regression ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Nucleotide Polymorphisms ◽

Chi Square ◽

Capsule Formation ◽

Host Interaction ◽

Chi Square Test ◽

Single Locus Analysis

Background. The presence of a capsule is an important prognostic factor in hepatocellular carcinoma (HCC). Capsule formation is affected by tumor-host interaction, which may include collagen deposition and extracellular matrix (ECM) degradation. Purpose. This study aimed to examine whether single-nucleotide polymorphisms (SNPs) in the genes for COL1A1 MUC15, MMP14, CD97, SMYD3, BRAF, and transforming growth factor beta 1 (TGF-β) are related to capsule formation. Methods. We prospectively recruited and analyzed 185 patients with HCC with or without a capsule between 2019 and 2020. The SNPs involved were analyzed by polymerase chain reaction. Differences in the allele and genotype frequency between the cases and controls were evaluated using the chi-square test. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis with adjustment for age and sex. Stratification analyses were also performed with preselected variables. Results. The single-locus analysis showed that the presence of a capsule was significantly associated with five SNPs : MUC15 rs17309195 P = 0.01 , rs12271124 P = 0.02 , rs10430847 P = 0.04 , MMP14 rs17884816 P = 0.01 , and BRAF rs74512895 P = 0.03 . Adjusted logistic regression revealed that the decreased capsule formation was statistically significantly associated with BRAF rs76603725, COL1A1 rs2269336, and MUC15 rs17309195, while MMP14 rs17884816 and MUC15 rs10430847, rs2063278, and rs967490 were associated with increased capsule formation. The MUC15 block 2 haplotype was associated with increased capsule formation. Conclusions. MUC15, MMP14, BRAF, and COL1A1 gene polymorphisms are associated with capsule formation in HCC. Studies involving larger samples are needed to confirm our results.

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Chronic Periodontitis and RANKL/OPG Ratio in Peri-Implant Mucosae Inflammation

Brazilian Dental Journal ◽

10.1590/0103-6440201801241 ◽

2018 ◽

Vol 29 (1) ◽

pp. 14-22 ◽

Cited By ~ 2

Author(s):

Lucas Carneiro Costa ◽

Marcos Alexandre da Fonseca ◽

Aristides da Rosa Pinheiro ◽

Telma Regina da Silva Aguiar ◽

Aldir Nascimento Machado ◽

...

Keyword(s):

Chronic Periodontitis ◽

Test Evaluation ◽

Continuous Variables ◽

Chi Square ◽

Protein Levels ◽

Rankl Mrna ◽

Chi Square Test ◽

History Of ◽

Single Blind ◽

Nominal Variables

Abstract tHistory of chronic periodontitis (CP) is a risk factor for oseointegration failure. The osteoclastogenesis system (RANK, RANKL and OPG) is critical for bone homeostatic control. We investigated the levels of OPG and RANKL in peri-implant tissues from volunteers with and without a history of CP and their association with mucosae inflammation. This is a single-blind case-contro study. Diagnosis of a history of CP and peri-implant examination was performed on 46 volunteers, divided into control (without history of CP, n=26) and CP group (with history of CP, n=20). Gingival biopsies were harvested during implant exposure. Quantitative PCR evaluated OPG/RANKL mRNA expressions. OPG and RANKL proteins were analyzed by western blot and immunohistochemistry assay. The chi-square test analyzed the significance of nominal variables between groups while continuous variables were analyzed by T-test or Mann-Whitney test, after Shapiro-Wilk test evaluation. The 2-ΔΔCT Livak method calculation evaluated the gene expression. Values of p<0.05 were considered statistically significant. Volunteers with CP history had 23 times higher chance of developing mucosae inflammation. High mucosae levels of RANKL (p=0.04) and RANKL/OPG (p=0.001) mRNA expressions were observed in CP group. CP volunteers showed increased RANKL protein levels in opposition to decreased OPG expression. Even without active periodontitis, volunteers with a history of CP had elevated gingival levels of RANKL/OPG and higher correlation with peri-implant mucosae inflammation and implant loss.

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RETRACTED: MicroRNA-367 promotes progression of hepatocellular carcinoma through PTEN/PI3K/AKT signaling pathway

Bioscience Reports ◽

10.1042/bsr20182466 ◽

2019 ◽

Cited By ~ 1

Author(s):

Zhihua Wang ◽

Yu Luo

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Akt Pathway ◽

Migration And Invasion ◽

Chi Square ◽

Western Blot Assay ◽

Functional Roles ◽

Elevated Expression ◽

Chi Square Test

The study aimed to investigate the functional roles of micorRNA (miR)-367 in progression of hepatocellular carcinoma (HCC), as well as its regulation on PI3K/AKT pathway. The relative expression of miR-367 in HCC tissues and cell line was detected using quantitative real-time polymerase chain reaction (qRT-PCR) method. Chi-square test was applied to analyze the relationship between miR-367 expression and clinical characterizes of HCC patients. The influences of miR-367 expression on cell proliferation, migration and invasion were analyzed using MTT and transwell assays respectively. Western blot assay was performed to for protein analysis. HCC tissues and cell lines exhibited significant up-regulation of miR-367. Moreover, the elevated expression of miR-367 was positively correlated with tumor size (P=0.005), metastasis (P=0.004) and TNM stage (P<0.001). Knockdown of miR-367 expression could inhibit cell proliferation, migration and invasion in vitro. While, enhanced miR-367 expression exhibited opposite effects. Besides, inhibition of miR-367 might enhance PTEN expression, reduce the levels of p-GSK3β and p-AKT. PTEN might be a target of miR-367 in HCC. The inhibition of PTEN could reverse the anti-tumor action caused by the knockdown of miR-367. MiR-367 serves as an oncogene in HCC through activating the PI3K/AKT pathway by targeting PTEN.

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Rab25 Acts as a Promising Novel Bio-Marker in the Prognosis of Patients with Hepatocellular Carcinoma

10.21203/rs.3.rs-43510/v1 ◽

2020 ◽

Author(s):

Zhong Dai ◽

Ke-Qing Yao ◽

Xing-Sheng Hu ◽

Yi-Qun Li ◽

Yu-Tao Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Value ◽

Cox Regression ◽

Rank Test ◽

Chi Square ◽

Cox Regression Analysis ◽

Normal Tissues ◽

Kaplan Meier ◽

Chi Square Test ◽

The Relationship

Abstract Background: Rab25 was indicated to be involved in several human tumors. However, the clinical significance of Rab25 in hepatocellular carcinoma (HCC) was still unclear. The purpose of this study was to investigate the expression and prognostic value of Rab25 in HCC.Methods: The relative mRNA expression levels of Rab25 in HCC tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was used to analyze the relationship between Rab25 expression and clinical characteristics of patients. The prognostic value of Rab25 in HCC was estimated through Kaplan-Meier method and cox regression analysis.Results: Rab25 gene expression level was significantly higher in HCC tissues than that in normal tissues (P<0.001). Importantly, the increased Rab25 expression was closely associated with TNM stage (P=0.024), metastasis (P=0.022) and invasion classification (P=0.039). Moreover, patients with high Rab25 expression tended to have obviously shorter overall survival than those with low expression of Rab25 (log rank test, P<0.001) via Kaplan-Meier analysis. Univariate and multivariate cox regression analyses revealed that Rab25 was an independent prognostic factor of HCC.Conclusions: Rab25 is up-regulated in HCC and contributes to the progression of this tumor. What’s more, Rab25 may be a potential bio-marker for the prognosis of HCC.

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