scholarly journals PIVKA-II serves as a potential biomarker that complements AFP for the diagnosis of hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Honglei Feng ◽  
Bole Li ◽  
Ze Li ◽  
Qian Wei ◽  
Li Ren

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels. Methods Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients. Results Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection. Conclusions PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.

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.


2021 ◽  
Author(s):  
Zhiyi Han ◽  
Wenxing Feng ◽  
Rui Hu ◽  
Qinyu Ge ◽  
Wenfeng Ma ◽  
...  

Abstract Background: Hepatocellular carcinoma with extremely high morbidity and mortality is one of the most common malignant tumors. Although many existing studies focus on the study of its biomarkers, little information has been released on the PBMC RNA profile of hepatocellular carcinoma. Methods: We tried to make a profile throughout this analysis with the expression of Peripheral Blood Mononuclear Cells (PBMCs) RNA by using RNA-seq technology and compared the transcriptome between hepatocellular carcinoma patients and the healthy controls. 17 patients and 17 healthy controls involved in this study, PBMCs RNA were sequenced. The sequencing data were analyzed with bioinformatics tools and qRT-PCR was used for selected differential expressed gene validation. Results: It is showed that 1578 dysregulated genes found including 1334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG studies showed that hepatocellular carcinoma is a closely linked source of the most differentially expressed genes (DEGs), implicated in the immune response. Expression of the 6 selected genes (SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) were confirmed by qRT-PCR, and higher sensitivity and specificity obtained by ROC analysis of the 6 genes. CALM1 was found gradually decreasing along with the tumor enlarged. Conclusions: It is suggested potential biomarker for diagnosis of hepatocellular carcinomas. This study provided new perspectives for liver cancer development and possible future successful clinical diagnosis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhiyi Han ◽  
Wenxing Feng ◽  
Rui Hu ◽  
Qinyu Ge ◽  
Wenfeng Ma ◽  
...  

AbstractHepatocellular carcinoma (HCC) is one of the most common malignant tumors and has extremely high morbidity and mortality. Although many existing studies have focused on the identification of biomarkers, little information has been uncovered regarding the PBMC RNA profile of HCC. We attempted to create a profile throughout using expression of peripheral blood mononuclear cell (PBMC) RNA using RNA-seq technology and compared the transcriptome between HCC patients and healthy controls. Seventeen patients and 17 matched healthy controls were included in this study, and PBMC RNA was sequenced from all samples. Sequencing data were analyzed using bioinformatics tools, and quantitative reverse transcription PCR (qRT-PCR) was used for selected validation of DEGs. A total of 1,578 dysregulated genes were found in the PBMC samples, including 1,334 upregulated genes and 244 downregulated genes. GO enrichment and KEGG studies revealed that HCC is closely linked to differentially expressed genes (DEGs) implicated in the immune response. Expression of 6 selected genes (SELENBP1, SLC4A1, SLC26A8, HSPA8P4, CALM1, and RPL7p24) was confirmed by qRT-PCR, and higher sensitivity and specificity were obtained by ROC analysis of the 6 genes. CALM1 was found to gradually decrease as tumors enlarged. Nearly the opposite expression modes were obtained when compared to tumor sequencing data. Immune cell populations exhibited significant differences between HCC and controls. These findings suggest a potential biomarker for the diagnosis of HCC. This study provides new perspectives for liver cancer development and possible future successful clinical diagnosis.


2021 ◽  
Author(s):  
Fei Liu ◽  
Ye Han ◽  
Dongbao Li ◽  
Jun Zhou ◽  
Jingjing Xu ◽  
...  

Abstract Gastric cancer (GC) is one of the most common malignant tumors with a leading cause of cancer-related mortality worldwide. Exosomal miRNAs are considered as promising non-invasive biomarkers for the diagnosis of malignant tumors. In this study, we aimed to investigate the expression of exosomal miR-17-92 cluster and develop a potential biomarker for the diagnosis of GC. Exosomal RNAs were extracted and the expression profile of miR-17-92 cluster was detected using quantitative polymerase chain reaction (qRT-PCR). The ROC (receiver-operating characteristic) curve and AUC (area under the ROC curve) analysis were used to explore the diagnostic utility of miRNAs. Statistical was used to analyze the expression of serum exosomal miR-17-92 cluster with the clinical pathological parameters of GC patients. The results showed that the expressions of four members of the exosomal miR-17-92 cluster in the serum samples of GC patients were significantly upregulated compared with those of healthy controls. The AUC for serum exosomal miR-17, miR-18, miR-19a and miR-92 was 0.750 (95%CI=0.626-0.874, sensitivity=84.7%, specificity=70.0%), 0.736 (95%CI=0.590-0.881, sensitivity=88.9%, specificity=65.0%), 0.700 (95%CI=0.562-0.838, sensitivity=62.5%, specificity=80.0%), 0.689 (95%CI=0.567-0.811, sensitivity=45.8%, specificity=90.0%), respectively. The AUC for the newly combined panel consisting of miR-17, miR-18, miR-19a and miR-92 was 0.808 (95%CI=0.680-0.937), with sensitivity of 90.3% and specificity of 70.0%, which showed much higher clinical diagnostic value for GC than any of the four alone or any pair. Besides, the AUC for the newly developed panel consisting of the two traditional tumor biomarkers including CEA (carcinoembryonic antigen) and CA19-9 (carbohydrate antigen 19-9) and the four miR-17-92 cluster members was 0.881 (95%CI, 0.765-0.998) with sensitivity of 91.7% and specificity of 90.0%, which showed the greatest powerful clinical diagnostic value for GC. Moreover, the elevated exosomal miR-17-92 expressions were closely correlated with tumor size, tumor depth, lymph node metastasis, distant metastasis and TNM stage of GC patients. In conclusion, our findings revealed that circulating exosomal miR-17-92 cluster may be used as a novel potential non-invasive biomarker to improve the diagnostic efficiency in GC.


Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1247
Author(s):  
Anne Worthington ◽  
Alise Kalteniece ◽  
Maryam Ferdousi ◽  
Luca Donofrio ◽  
Shaishav Dhage ◽  
...  

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2–4 and 2–5 at 1 Hz, AUC = 0.84 (95%CI 0.76–0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.


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.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jinlan Huang ◽  
Yansong Zheng ◽  
Xialin Xiao ◽  
Can Liu ◽  
Jinpiao Lin ◽  
...  

Background. Circulating long noncoding RNAs (lncRNAs) have been demonstrated to serve as diagnostic biomarkers for various cancers. We aimed to elucidate the diagnostic efficacy of eight serum lncRNAs HULC, MALAT1, Linc00152, PTENP1, PTTG3P, SPRY4-IT1, UBE2CP3, and UCA1 and their combinations for the diagnosis of hepatocellular carcinoma (HCC). Methods. A total of 129 patients with HCC, 49 patients with liver cirrhosis, 27 patients with chronic hepatitis B, and 93 healthy controls were enrolled in this study. The levels of serum lncRNAs were assessed by quantitative real-time polymerase chain reaction. The correlations between serum lncRNAs and clinicopathological characteristics were further analyzed. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to estimate the diagnostic capacity of serum lncRNAs and their combination with AFP for HCC. A logistic regression model was performed to establish a multiple-lncRNA panel. Results. The levels of serum HULC, MALAT1, Linc00152, PTTG3P, SPRY4-IT1, UBE2CP3, and UCA1 were significantly higher in HCC patients than in patients with benign liver diseases and healthy controls, whereas serum PTENP1 was significantly decreased in HCC patients compared with healthy participants. Positive correlations between serum Linc00152 and GGT, serum PTTG3P and GGT, and serum SPRY4-IT1 and ALT were noted in HCC patients. ROC analysis revealed that all these lncRNAs had a significantly predictive value for HCC except for PTENP1. The best performance of single lncRNA was obtained by Linc00152 with an AUC of 0.877. When combined with AFP, the combination of Linc00152 and AFP gained the highest accuracy, yielding an AUC of 0.906. Through logistic regression analysis, the panel consisting of serum linc00152, UCA1, and AFP provided the greatest predictive ability, obtaining an AUC of 0.912 with 82.9% sensitivity and 88.2% specificity. Conclusion. The panel of serum Linc00152, UCA1, and AFP demonstrates a novel and noninvasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.


2020 ◽  
Vol 6 (5) ◽  
Author(s):  
Hubert Blum

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not significantly improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and the limited therapeutic options. The therapeutic options fall into several categories: (i) surgical interventions including tumor resection and liver transplantation, (ii) percutaneous interventions including ethanol injection and radiofrequency thermal ablation, (iii) transarterial interventions including embolization, chemoembolization and selective internal radiotherapy, (iv) external radiation therapy and (v) systemic strategies with cytotoxic agents and molecularly targeted therapies as well as immunotherapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for actual therapeutic recommendations. While surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, <5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% of patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care (BSC). In order to reduce the morbidity and mortality from HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including cytotoxic agents, molecular targeted and immunotherapies is most important. New analytical technologies, including gene expression profiling and proteomic analyses and others, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiuhua Liu ◽  
Cuijie Zhou ◽  
Bo Zhang

Abstract Background Hepatocellular carcinoma (HCC) is a common human malignant cancer due to a high metastatic capacity and the recurrence rate is also high. This study is aim to investigate the role of musashi1 as a potential biomarker for therapy of HCC. Methods The mRNA and protein expression levels of musashi1 were detected in HCC samples and cell lines. The malignant properties of HCC cells, including proliferation, invasion and migration were measured by overexpressing or knocking down expression of musashi1. Additionally, the correlation between musashi1 and clinicopathological indexes and prognosis were analyzed. The expression of CD44 was measured and the correlation between CD44 and musashi1 was analyzed. Results In vitro cytological experiments demonstrated that musashi1 was elevated in HCC samples and cell lines and this increased expression affected cancer cell viability, migration and invasive capacity by activating of the Wnt/β-catenin signaling pathway. Analysis of clinicopathological characteristics suggested that up-regulation of musashi1 was related to metastasis potential and a poor prognosis. Besides, there was a positive correlation between CD44 and musashi1 expression. Upregulation of musashi1 in malignant liver tumors may have contributed to the maintenance of stem-cell like characteristics of HCC cells. Conclusions Upregulation of musashi1 could enhance malignant development of HCC cells and thus might be a novel marker for HCC therapy.


2017 ◽  
Vol 10 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Puth Muangpaisarn ◽  
Kanisa Jampoka ◽  
Sunchai Payungporn ◽  
Naruemon Wisedopas ◽  
Chalermrat Bunchorntavakul ◽  
...  

Abstract Background MicroRNA-34a (miR-34a) contributes to liver injury through an apoptosis pathway. Objective To determine the correlation between serum miR-34a and liver inflammation as assessed by nonalcoholic fatty liver disease (NAFLD) activity score (NAS). Method We included a cross-selectional study of 50 patients with NAFLD in this observational study and confirmed diagnosis by liver biopsy, with NAS grading. A control group comprised 23 healthy individuals without chronic liver disease. Serum miR-34a was assayed using a real-time quantitative PCR (Applied Biosystems). Result The mean age of NAFLD patients was 46.0 ± 13.7 years, and 52% were female. Metabolic syndrome was found in 76%. Liver histopathology showed that 54% of patients had NAS ≥4 and significant fibrosis (≥2) was found in 22%. Serum levels of miR-34a were significantly correlated with NAS (r = 0.39, P = 0.005), and the degree of steatosis (r = 0.28, P = 0.049), ballooning (r = 0.30, P = 0.034), and fibrosis (r = 0.39, P = 0.005). Serum miR-34a in patients with NAS ≥4 was significantly higher than in those with NAS <4 (P = 0.011) and controls (P < 0.001). There was no significant correlation between serum miR-34a and other variables. The area under receiver operating characteristic curve for serum miR-34a comparing patients with NAS ≥4 and with NAS <4 was 0.67 (95% CI 0.52, 0.82). Conclusion Serum level of miR-34a has a significant fair to good correlation with NAS and may serve as a biomarker of liver inflammation and fibrosis in patients with NAFLD.


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