scholarly journals Serum long noncoding RNA urothelial carcinoma-associated 1: A novel biomarker for diagnosis and prognosis of hepatocellular carcinoma

2017 ◽  
Vol 46 (1) ◽  
pp. 348-356 ◽  
Author(s):  
Zhi-kun Zheng ◽  
Cui Pang ◽  
Yang Yang ◽  
Qiong Duan ◽  
Ju Zhang ◽  
...  

Objective Long noncoding RNAs (lncRNAs) offer great potential as cancer biomarkers. This study was performed to assess the applicability of serum lncRNA urothelial carcinoma-associated 1 (UCA1) as a diagnostic and/or prognostic biomarker for hepatocellular carcinoma (HCC). Methods We examined UCA1 expression in serum samples from 105 patients with HCC, 105 patients with benign liver disease (BLD), and 105 healthy volunteers using reverse-transcription polymerase chain reaction and analyzed the relationship between serum UCA1 and clinicopathological parameters of HCC as well as survival. Results Expression of serum UCA1 was significantly higher in patients with HCC and allowed for discrimination of HCC from BLD and healthy controls. High expression of serum UCA1 was significantly associated with a high tumor grade, large tumor size, positive vascular invasion, and advanced TNM stage. Multivariate analysis revealed that a high serum UCA1 level was an independent unfavorable prognostic factor for HCC. Conclusions Our results confirm the upregulation of serum UCA1 expression in HCC and indicate its clinical value as a noninvasive biomarker for HCC screening and prognostic prediction.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li Zhang ◽  
Hao Niu ◽  
Ping Yang ◽  
Jie Ma ◽  
Bao-Ying Yuan ◽  
...  

Abstract Background Early screening and intervention therapies are crucial to improve the prognosis of hepatocellular carcinoma (HCC) patients with bone metastasis. We aimed to identify serum lncRNA as a prediction biomarker in HCC bone metastasis. Methods The expression levels of lnc34a in serum samples from 157 HCC patients were detected by quantitative real-time polymerase chain reaction (PCR). Univariate analysis and multivariate analysis were performed to determine statistically significant variables. Results Expression levels of lnc34a in serum from HCC patients with bone metastasis were significantly higher than those without bone metastasis. The high expressions of lnc34a, vascular invasion and Barcelona Clinic Liver Cancer (BCLC) stage were associated with bone metastasis by analysis. Moreover, lnc34a expression was specifically associated with bone metastasis rather than lung or lymph node metastasis in HCC. Conclusions High serum lnc34a expression was a independent risk factor for developing bone metastasis in HCC.


2018 ◽  
Vol 64 (8) ◽  
pp. 1230-1238 ◽  
Author(s):  
Hyunsoo Kim ◽  
Areum Sohn ◽  
Injoon Yeo ◽  
Su Jong Yu ◽  
Jung-Hwan Yoon ◽  
...  

Abstract BACKGROUND Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) is a serum biomarker for hepatocellular carcinoma (HCC). AFP-L3 is typically measured by liquid-phase binding assay (LiBA). However, LiBA does not always reflect AFP-L3 concentrations because of its low analytical sensitivity. Thus, we aimed to develop an analytically sensitive multiple reaction monitoring–mass spectrometry (MRM-MS) assay to quantify AFP-L3 in serum. METHODS The assay entailed the addition of a stable isotope-labeled internal standard protein analog, the enrichment of AFP using a monoclonal antibody, the fractionation of AFP-L3 using L. culinaris agglutinin lectin, deglycosylation, trypsin digestion, online desalting, and MRM-MS analysis. The performance of the MRM-MS assay was compared with that of LiBA in 400 human serum samples (100 chronic hepatitis, 100 liver cirrhosis, and 200 HCC). Integrated multinational guidelines were followed to validate the assay for clinical implementation. RESULTS The lower limit of quantification of the MRM-MS assay (0.051 ng/mL) for AFP-L3 was less than that of LiBA (0.300 ng/mL). Thus, AFP-L3, which was not observed by LiBA in HCC samples (n = 39), was detected by the MRM-MS assay, improving the clinical value of AFP-L3 as a biomarker by switching to a more analytical sensitive platform. The method was validated, meeting all the criteria in integrated multinational guidelines. CONCLUSIONS Because of the lower incidence of false-negative findings, the MRM-MS assay is more suitable than LiBA for early detection of HCC.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yu-Ling Chen ◽  
Chien-Hung Chen ◽  
Rey-Heng Hu ◽  
Ming-Chih Ho ◽  
Yung-Ming Jeng

Serum levels of the tumor marker CA19-9 have been reported to be elevated in patients with hepatocellular carcinoma (HCC), but its clinicopathologic significance is still unknown. A cohort of 304 patients undergoing surgical resection for HCC and having preoperative CA19-9 data was enrolled in this study. Serum CA19-9 levels were correlated with clinicopathologic factors. Univariate and multivariate analyses were performed to determine the predictors of patient survival. On receiver operating characteristic curve analysis, the cut off value of CA19-9 was determined to be 27 U/mL. One hundred and six patients had preoperative CA19-9 values >27 U/mL. High serum CA19-9 levels did not correlate with patient age, sex, viral status,α-fetoprotein level, tumor size, tumor grade, tumor stage, multiplicity, and vascular invasion. Patients with elevated preoperative CA19-9 levels had lower 10-year survival than those without CA19-9 elevation. Multivariate analysis revealed that CA19-9 level, tumor grade, and tumor size are independent prognostic factors for long-term survival. In conclusion, a preoperative CA19-9 value >27 U/mL is associated with poor prognosis after resection for HCC.


2018 ◽  
Vol 7 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Yang Lv ◽  
Xu Han ◽  
Chunyan Zhang ◽  
Yuan Fang ◽  
Ning Pu ◽  
...  

Purpose Chromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs). Patients and Methods In this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers’ concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as P value less than 0.05. Results Among the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 μg/L (P < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, P < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration (P < 0.001); changes in CgA and NSE concentrations also reflect treatment response (P < 0.001). Conclusion CgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.


Author(s):  
Henk te Velthuis ◽  
Ingrid Knop ◽  
Peter Stam ◽  
Monic van den Broek ◽  
Hannie Klaasse Bos ◽  
...  

AbstractHigh serum concentrations of monoclonal free light chain (FLC) kappa or lambda are markers of plasma cell dyscrasia.We developed new, latex-enhanced, specific nephelometric assays based on monoclonal antibodies for the determination of FLC kappa and lambda in serum, EDTA plasma and Li-heparin plasma for use on the Siemens BN™ systems.Reference ranges were determined from 369 samples: FLC kappa 6.7–22.4 mg/L, FLC lambda 8.3–27.0 mg/L and kappa/lambda ratio 0.31–1.56. Protection from falsely low results due to antigen excess is obtained with a built-in pre-reaction in the assay protocols. Lot-to-lot consistency between three different lots of reagent, calibrators and supplementary reagent lots showed normalized differences <7.5%. The reproducibility of serum samples varied between 4% and 7%. The method comparison with Freelite™ assays showed normalized differences of 19.7%, 32.7% and 21.7%, respectively, for FLC kappa, lambda and ratio, correlations of 0.94, 0.77 and 0.73, and concordance rates of 99.2%, 94.2% and 95%.N Latex FLC demonstrates high precision, good lot-to-lot consistency and freedom from a high-dose hook effect. The method comparison between Freelite™ and the N Latex FLC assays showed good clinical concordance. Further studies need to reveal the clinical value of the new FLC assays.


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.


2021 ◽  
Vol 10 ◽  
Author(s):  
Juanni Li ◽  
Kuan Hu ◽  
Dongren He ◽  
Lei Zhou ◽  
Zhiming Wang ◽  
...  

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with no curative treatments. Plexin D1 (PLXND1) is a cellular receptor whose functions have been explored in several human cancers; however, the critical roles of PLXND1 in HCC have rarely been probed. Therefore, the present study attempted to elucidate the expression pattern, prognostic significance, and potential roles of PLXND1 in HCC. We found that PLXND1 expression in HCC tissues was significantly higher compared with normal liver tissue from Gene Expression Profiling Interactive Analysis (GEPIA) and Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB) databases. This result was further validated by immunohistochemistry staining (IHC) using tissue microarrays, which contained 216 HCC cases collected from our hospital. Additionally, PLXND1 expression showed a significant correlation with several clinical characteristics, including tumor grade and tumor hemorrhage (TH). Moreover, TISIDB and GEPIA databases were used to investigate the roles of PLXND1 in tumor-immune system interactions in HCC. As an immunoinhibitor, transforming growth factor-beta (TGF-β1) displayed the greatest correlations with PLXND1 in HCC. Finally, Kaplan-Meier curves and Cox analysis were conducted to further examine the potential clinical value of PLXND1 in HCC. We described a subclassification of HCC based on PLXND1 and TGF-β1 expression, which could be used to predict clinical outcomes and patient prognosis. Taken together, the results of this study indicate that PLXND1 might be a promising prognostic biomarker and potential therapeutic target in HCC.


Epigenomics ◽  
2021 ◽  
Author(s):  
Yanlin Feng ◽  
Souraka Tapara Dramani Maman ◽  
Xinyu Zhu ◽  
Xuefang Liu ◽  
Christian Cedric Bongolo ◽  
...  

This study aimed to unveil the functional roles of LINC00221 in hepatocellular carcinoma (HCC). A discovery cohort and a validation cohort were respectively used to identify and verify the clinical value of LINC00221 in HCC. Bioinformatics analysis was performed to explore its potential mechanisms. LINC00221 was upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve further revealed its prognostic and diagnostic roles. Exploration of the mechanism showed that LINC00221 might exert a pro-cancer role via the lncRNA–miRNA–mRNA network. Our study reveals that upregulated LINC00221 can serve as a potential diagnostic and prognostic biomarker and provides novel clues as to the role of LINC00221 in HCC.


2020 ◽  
Vol 16 (13) ◽  
pp. 827-835
Author(s):  
Ye Ding ◽  
Wei Feng ◽  
Jian-kang Ge ◽  
Lu Dai ◽  
Ting-ting Liu ◽  
...  

Aim: Long noncoding RNA (lncRNA) B3GALT5-AS1 has been reported as a biomarker for cancer monitoring. This research aims to identify serum long noncoding RNA B3GALT5-AS1 as a new biomarker for the diagnosis of colorectal cancer (CRC) and evaluate its clinical value. Materials & methods: Serum B3GALT5-AS1 expression levels were measured by quantitative real-time PCR. Results: The level of B3GALT5-AS1 in CRC patients was significantly lower than that of healthy patients (p < 0.0001). Further exploration validated that high serum B3GALT5-AS1 level was related to tumor node metastasis (TNM) stage (p = 0.008) and histological differentiation (p = 0.027). Compared with the healthy control group, AUCROC of serum B3GALT5-AS1 in the CRC group was 0.762 with 95% CI: 0.698–0.826 (p < 0.0001). Conclusion: B3GALT5-AS1 may be served as a diagnostic marker for distinguishing CRC patients from healthy people.


2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Jie Ma ◽  
Li Zhang ◽  
Hai-Rong Bian ◽  
Zheng-Guo Lu ◽  
Lian Zhu ◽  
...  

Background and Objectives. Lymph node metastasis (LNM) is common in hepatocellular carcinoma (HCC). In order to intervene HCC LNM in advance, we developed a prediction nomogram based on serum long noncoding RNA (lncRNA). Methods. Serum samples from 242 HCC patients were gathered and randomly enrolled into the training and validation cohorts. LncRNAs screened out from microarray were quantified with qRT-PCR. Univariate and multivariate analyses were applied for screening independent risk factors. A prediction nomogram was ultimately developed for HCC LNM. The nomogram was estimated by discrimination and calibration tests in the validation cohort. The effects of the candidate lncRNA on the malignant phenotypes of HCC cells were further explored by wound healing assay and colony formation assay. Results. ENST00000418803, lnc-ZNF35-4:1, lnc-EPS15L1-2:1, BCLC stage, and vascular invasion were selected as components of the nomogram according to the adjusted multivariate analysis. The nomogram effectively predicted the HCC LNM risk among the cohorts with suitable calibration fittings and displayed high discrimination with C-index of 0.89 and 0.85. Moreover, the abnormally high expression of lnc-EPS15L1-2:1 in HCC cell lines showed significant carcinogenic effects. Conclusions. The noninvasive nomogram may provide more diagnostic basis for treatments of HCC. The biomarkers identified can bring new clues to basic researches.


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