Faculty Opinions recommendation of EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma.

Author(s):  
Malcolm Alison
BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongdong Zhou ◽  
Xiaoli Liu ◽  
Xinhui Wang ◽  
Fengna Yan ◽  
Peng Wang ◽  
...  

Abstract Background Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. Methods A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. Results The C-index of nomogram1was 0.708 (95%CI: 0.673–0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606–0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690–0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691–0.813; AUC: 0.784, 95%CI: 0.709–0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. Conclusions Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.


2021 ◽  
Author(s):  
Masatoshi Kudo ◽  
Masafumi Ikeda ◽  
Peter R. Galle ◽  
Tatsuya Yamashita ◽  
Richard S. Finn ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Abd El-Fattah F. Hanno ◽  
Fatma M. Abd El-Aziz ◽  
Akram A. Deghady ◽  
Ehab H. El-Kholy ◽  
Aborawy I. Aborawy

Abstract Background Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Early stages of hepatocellular carcinoma (0&A) can be treated with curative procedures. The aim of this work was to evaluate the role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis C virus patients. Methods The study was carried out on 80 patients classified into two groups. Group A had 40 chronic hepatitis C patients without hepatocellular carcinoma, while group B had 40 chronic hepatitis C patients with early hepatocellular carcinoma (stages; 0&A). All patients were subjected to thorough history taking, clinical examination, liver function tests, renal function tests, serum alpha-fetoprotein, serum osteopontin, and serum annexin A2. Results Serum alpha-fetoprotein was found to be statistically significantly higher in patients with the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for alpha-fetoprotein for detection of HCC was significant, its diagnostic performance was 0.818* (p < 0.001*), and the cutoff point for predicting the probability for HCC was 6.0 (ng/ml) with sensitivity of 77.50%, specificity of 82.50%, positive predictive value of 81.60%, negative predictive value of 78.6%, and accuracy of 80%. Serum osteopontin was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for osteopontin was significant, its diagnostic performance was 0.739* (p < 0.001*), the cutoff point was 13.2 (ng/ml) with sensitivity of 65.0%, specificity of 90.0%, positive predictive value of 86.70%, negative predictive value of 72.0%, and accuracy of 77.0%. Serum annexin A2 was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for annexin A2 was significant, its diagnostic performance was 0.927* (p < 0.001*), the cutoff point was 10.1(ng/ml) with sensitivity of 85.0%, specificity of 85.0%, positive predictive value of 85.0%, negative predictive value of 85.0%, and accuracy of 85.0%. Conclusions Osteopontin had better specificity but lower sensitivity than serum alpha-fetoprotein for early diagnosis of hepatocellular carcinoma. Annexin A2 had better diagnostic sensitivity and specificity than alpha-fetoprotein for early diagnosis of hepatocellular carcinoma.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kung-Hao Liang ◽  
Ming-Wei Lai ◽  
Yang-Hsiang Lin ◽  
Yu-De Chu ◽  
Chih-Lang Lin ◽  
...  

Abstract Background Predicting imminent hepatocellular carcinoma (HCC) in liver cirrhotic patients is an unmet medical need. We aimed to investigate circulatory biomarkers and their optimum combinations in a prospective study. Methods We investigated plasma interleukin 17 (IL-17) concentrations, quantified using enzyme-linked immunosorbent assay (ELISA), for the prediction of HCC in a large cohort of 404 HCC-naïve liver cirrhotic patients regularly followed after recruitment. Additionally, IL-17 in surgically resected tumor tissues were evaluated using immunohistochemistry staining. Results IL-17 was detected in HCC tissues. The IL-17 concentrations in the peripheral blood do not have correlation with an extensive list of 31 common demographic, metabolic and liver function variables in the cohort of liver cirrhotic patients. Furthermore, patients stratified by IL-17 and alpha-fetoprotein (AFP) showed distinctive cumulative incidence of HCC. Imminent HCC, defined here as HCC occurrence within 1 year, can be predicted by IL-17 alone with an area under the receiver operating characteristic curve [AUC] of 0.762 (P = 0.002). An multivariate analysis showed that age, hepatitis C viral infection, AFP and IL-17 were four independent factors associated with imminent HCC (adjusted P = 0.03, 0.041, 0.024 and 0.008 respectively). An explicit risk score (R) combining the concentrations of two plasma biomarkers, AFP and IL-17, achieved a high AUC of 0.933 (95% confidence interval 0.893–0.972, P < 0.001) in predicting imminent HCC, with 100% sensitivity and 79.9% specificity at the optimum cutoff. The score is defined as: $${\text{R}} = (2.6914)*{\text{IL-17}} + (0.3909)*{\text{AFP}} - (0.80812875)*{\text{IL-17}}^{2} + (0.10288876884)*{\text{IL-17}}^{2} *{\text{AFP}}.$$ R = ( 2.6914 ) ∗ IL-17 + ( 0.3909 ) ∗ AFP - ( 0.80812875 ) ∗ IL-17 2 + ( 0.10288876884 ) ∗ IL-17 2 ∗ AFP . Conclusions The circulatory IL-17 concentration is a predictor of subsequent HCC occurrence in liver cirrhotic patients. The combination of AFP and IL-17 is highly effective in predicting imminent HCC within 1 year.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shanshan Wang ◽  
Rilu Feng ◽  
Ying Shi ◽  
Dexi Chen ◽  
Honglei Weng ◽  
...  

AbstractRetinoic acid and retinoid acid receptor (RA-RAR) signaling exhibits suppressive functions in the progression of hepatocellular carcinoma (HCC) through multiple mechanisms. However, whether RA-RAR signaling induces autophagy that contributes its anti-tumor activity in HCC remains elusive. In the current study, the effects of RA-RAR pathway on autophagy were investigated in two HCC cell lines: alpha-fetoprotein (AFP) positive PLC/PRF/5 and AFP negative HLE cells. Cell autophagy was analyzed with western blot for detection of LC3 conversion and p62/SQSTM1 degradation while autophagy flux was assayed using the mRFP-GFP-LC3 reporter. Cell apoptosis and viability were analyzed by caspase-3 activity, TdT-mediated dUTP nick end labeling (TUNEL) assay, and Cell Counting Kit (CCK)-8, respectively. Chromatin immunoprecipitation (ChIP) was employed to detect the binding of RAR onto the promoter of autophagy-relevant 7 (ATG7), and co-immunoprecipitation (CoIP) was used to analyze the interaction of AFP and RAR. The results showed that ATRA dosage and time-dependently induced high levels of cell autophagy in both the PLC/PRF/5 and HLE cells, which was accompanied with up-regulation of ATG7. ChIP assay showed that RAR was able to bind to its responsive elements on ATG7 promoter. Impairment of ATG7 induction or blockade of autophagy with chloroquine aggravated ATRA induced apoptosis of HCC cells. Furthermore, intracellular AFP was able to complex with RAR in PLC/PRF/5 cells. Knockdown of AFP in PLC/PRF/5 cells augmented the up-regulation of ATG7 by ATRA while overexpression of AFP in HLE cells attenuated ATRA induced ATG7 expression and autophagy. Thus, ATRA induced ATG7 and autophagy participated in its cytotoxicity on HCC cells and AFP interfere with the induction of ATG7 and autophagy through forming complex with RAR.


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