Combined Detection of mRNA Expression of Alpha-Fetoprotein in Peripheral Blood and Telomerase Activity of Monocytes in Hepatocellular Carcinoma Patients

Author(s):  
Yu-Kun Huang ◽  
Xue-Gong Fan ◽  
Fu Qiu ◽  
Zhi-Ming Wang
2013 ◽  
Vol 35 ◽  
pp. 915-923 ◽  
Author(s):  
Zhuqingqing Cui ◽  
Xin Yu ◽  
Limin Guo ◽  
Yuhua Wei ◽  
Shengmin Zheng ◽  
...  

We investigated the feasibility of the combined detection of HLA-A2/MAGE-A3 epitope-specific cytotoxic T lymphocytes (CTLs) and serum alpha-fetoprotein (AFP) for specific diagnosis of hepatocellular carcinoma (HCC). We detected the frequency of MAGE-A3 epitopes (p112–120, KVAELVHFL) in spontaneous CTLs in the peripheral blood of HCC patients, liver cirrhosis patients, and healthy subjects with HLA-A2/polypeptide complex (pentamer) detection technology. Eighty-five HCC cases, 38 liver cirrhosis cases, and 50 healthy cases who were HLA-A2-positive were selected from 175 HCC patients, 80 patients with liver cirrhosis, and 105 healthy volunteers, respectively. The frequency of HLA-A2-specific MAGE-A3+CTLs in the HCC group was significantly higher than that in the other groups. Combined detection of MAGE-A3+CTL frequency and serum AFP value had a higher specificity than either of the two indicators alone. The pentamer technique is helpful in distinguishing benign lesions and malignant lesions in the liver. Combined with serum AFP, it can improve the diagnosis performance for HCC, especially for AFP-negative cancer.


MedPharmRes ◽  
2021 ◽  
Vol 5 (4) ◽  
pp. 12-26
Author(s):  
Rita Ammoury ◽  
Roula Tahtouh ◽  
Nadine Mahfouz ◽  
Raia Doumit ◽  
Charbel Khalil ◽  
...  

Protein kinase C (PKC) family has been an alluring objective for new cancer drug discovery. It has been reported to regulate telomerase in several cancer types. Our team had previously used telomerase to elucidate alpha-fetoprotein (AFP) modulation in hepatocellular carcinoma (HCC). The aim of this study was to investigate the interrelationships among PKC isoforms, telomerase and AFP in HCC. PKCα and PKCδ were the most expressed isoforms in HepG2/C3A, PLC/PRF/5, SNU-387 and SKOV-3 cells. Following the upregulation of AFP using pCMV3-AFP and the human telomerase reverse transcriptase (hTERT) using a construct expressing a wild-type hTERT, and after their inhibition with all-trans retinoic acid and hTERT siRNA each respectively, we found that the expression of PKCα, PKCβI, PKCβII and PKCδ was affected by the variation of AFP and hTERT mRNA levels. An increase in AFP expression and secretion was observed after gene silencing of PKCα, PKCβ, PKCδ, and PKCε in HepG2/C3A. A similar pattern was observed in transfected PLC/PRF/5 cells, however PKCδ isoform silencing decreased AFP expression. Furthermore, telomerase activity was quantified using quantitative telomeric repeat amplification protocol. The variations in hTERT expression and telomerase activity were similar to those of AFP. Further investigation showed that PKC isoforms regulate AFP and hTERT expression levels through PI3K/AKT/mTOR pathway in HepG2/C3A and PLC/PRF/5 cells. Thus, these results show for the first time a possible interrelationship that links PKC isoforms to both AFP and hTERT via PI3K/AKT/mTOR pathway in HCC.


2011 ◽  
Vol 18 (8) ◽  
pp. 2200-2209 ◽  
Author(s):  
Shigeru Marubashi ◽  
Hiroaki Nagano ◽  
Hiroshi Wada ◽  
Shogo Kobayashi ◽  
Hidetoshi Eguchi ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Shao Wei Hu ◽  
Meng Zhang ◽  
Ling Xue ◽  
Jian Ming Wen

Aim. To investigate the relationship between alpha-fetoprotein and zinc fingers and homeoboxes 2 in hepatocellular carcinoma.Materials and Methods. The expressions of zinc fingers and homeoboxes 2, nuclear factor-YA, and alpha-fetoprotein mRNA in 63 hepatocellular carcinoma were detected by reverse transcriptase-polymerase chain reaction and compared with the clinical parameters of the patients. Selectively, silence of zinc fingers and homeoboxes 2 in HepG2 cells was detected by RNA interference technique.Results. Alpha-fetoprotein mRNA expression was detected in 60.3% of hepatocellular carcinoma cases. Zinc fingers and homeoboxes 2 mRNA expression (36.5%) was significantly negatively correlated with serum alpha-fetoprotein concentration and mRNA expression. A strong positive correlation was found between zinc fingers and homeoboxes 2 and nuclear factor-YA mRNA expression (42.9%), while the latter was negatively correlated with serum alpha-fetoprotein concentration and mRNA expression. Treatment with zinc fingers and homeoboxes 2 small interfering RNA led to 85% and 83% silence of zinc fingers and homeoboxes 2 mRNA and protein expression and 60% and 61% reduction of nuclear factor-YA mRNA and protein levels in the HepG2 cells, respectively. Downregulation of zinc fingers and homeoboxes 2 also induced a 2.4-fold increase in both alpha-fetoprotein mRNA and protein levels.Conclusions. Zinc fingers and homeoboxes 2 can regulate alpha-fetoprotein expression via the interaction with nuclear factor-YA in human hepatocellular carcinoma and may be used as an adjuvant diagnostic marker for alpha-fetoprotein-negative hepatocellular carcinoma.


2021 ◽  
Author(s):  
Huaxiang Wang ◽  
Fengfeng Feng Xu ◽  
Lizhi Lv ◽  
Ruling Wang ◽  
Bin Jiang ◽  
...  

Abstract Background Chaperonin containing TCP1 subunit 7 (CCT7), a member of the chaperonin containing TCP1 complex (CCT), has been reported regulating the expression of many tumor-related proteins. In this study, we investigated the diagnostic and prognostic value of CCT7 expression for hepatocellular carcinoma (HCC). Methods We investigated the CCT7 expression in HCC in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and our cohort. The diagnostic and prognostic value were verified by receiver operating characteristic curve (ROC) analysis and Kaplan-Meier analysis, respectively. The association between CCT7 expression with DNA methylation status was investigated in the TCGA database. Gene ontology (GO), The Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analysis were employed to identify the potential pathway in which CCT7 is involved in tumorigenesis and progression. Results CCT7 expression in HCC was significantly higher than adjacent normal tissues, and elevated CCT7 expression correlated with tumor stages and tumor grade. Furthermore, the ROC curve showed CCT mRNA expression has a better diagnostic value for HCC with early-stage and low alpha-fetoprotein expression. Positive predictive value (PPV) of CCT7 was higher than alpha-fetoprotein both in the GEO and TCGA database. The Multivariate Cox Regression analysis of clinicopathologic characteristics revealed that both high mRNA and protein expression of CCT7 were independent risk factors for overall survival (OS) and recurrence-free survival (RFS). High DNA methylation of CpG site(cg19515186) was associated with low CCT7 expression and better OS in HCC. The GO, KEGG and GSEA analysis demonstrated that CCT7 mRNA expression was associated with Spliceosome signaling pathway. Conclusions The findings of this study demonstrated that CCT7 has diagnostic and prognostic value for HCC.


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