scholarly journals Decreased Expression of KPNA2 in Hepatocellular Carcinoma Infers Favorable Prognosis and High Immune Infiltrating Level

Author(s):  
kangming zhu ◽  
yvndi zhang ◽  
hui yvan ◽  
jing li

Abstract BackgroundLiver hepatocellular carcinoma (LIHC) is an important pathological type of liver cancer. The immune infiltration of the tumor microenvironment is negatively correlated with the overall survival rate of LIHC. At present , the role and molecular mechanism of KPNA2 in LIHC have not been elucidated, and the prognostic correlation between the two and the immune infiltration of LIHC are still unclear. Our study evaluated the role of KPNA2 in LIHC through TCGA data.MethodGene expression profiling interactive analysis (GEPIA) is used to analyze the expression of KPNA2 in LIHC. We evaluated the impact of KPNA2 on the survival of LIHC patients through the survival module. Then, We downloaded the LIHC data set from TCGA. Logistic regression was used to analyze the correlation between clinical information and KPNA2 expression. Cox regression analysis was used to analyze the clinicopathological characteristics related to the overall survival rate of TCGA patients. In addition, we used the "correlation" modules of CIBERSORT and GEPIA to explore the correlation between KPNA2 and cancer immune infiltrate. Western blotting was used to detect the expression of KPNA2.ResultUsing logistic regression for univariate analysis, increased KPNA2 expression was significantly correlated with pathological stage, tumor status, and lymph node status. In addition, multivariate analysis showed that down-regulation of KPNA2 expression, negative pathological stage and distant metastasis are independent prognostic factors for good prognosis. Specifically, CIBERSORT analysis was used to establish a negative correlation between the up-regulated expression of KPNA2 and the level of immune infiltration of B cells, NK cells, mast cells, and T cells. In addition, we confirmed this in the "Association" module of GEPIA. The expression of KPNA2 in LIHC tissues was significantly lower than that in adjacent normal tissues by western blotting.ConclusionThe down-regulation of KPNA2 expression is associated with a good prognosis and an increase in the proportion of immune cells in LIHC. These conclusions indicate that KPNA2 is related to the level of immune infiltration of LIHC and can be used as a potential prognostic biomarker of LIHC and a potential target for clinical tumor treatment.

Liver Cancer ◽  
2021 ◽  
Author(s):  
Jinli Zheng ◽  
Wei Xie ◽  
Yunfeng Zhu ◽  
Li Jiang

Hepatectomy is still as the first-line treatment for the early stage HCC, but the complication rate is higher than p-RFA and the overall survival rate is comparable in these two treatments. Therefore, the patients with small single nodular HCCs could get more benefit from p-RFA, and we need to do further research about p-RFA.


2011 ◽  
Vol 30 (6) ◽  
pp. 325-333 ◽  
Author(s):  
Mei-Lin Chen ◽  
Chee-Yin Chai ◽  
Kun-Tu Yeh ◽  
Shen-Nien Wang ◽  
Chia-Jung Tsai ◽  
...  

C-Src activity is regulated by tyrosine phosphorylation at two distinct sites, Tyr416 and Tyr527, with opposite effects. However, the clinical roles of these sites in human cancers are not well defined. This study aims to determine whether the alterations and crosstalk of these two sites may contribute to hepatocellular carcinoma (HCC). Specimens from 85 patients who had undergone curative hepatectomy were collected for this study. The patterns of p-Tyr416-Src and p-Tyr527-Src, as well as the non-phosphorylated status for each site, were determined using immunohistochemistry and statistically correlated with clinicopathological characteristics and overall survival rate. The active state of c-Src, p-Tyr416-c-Src, was positively correlated with tumour grade (P= 0.062) but inversely correlated with vascular invasion (P= 0.071). Its non-phosphorylated status, non-p-Tyr416-c-Src, was positively correlated with tumour stage and grade (P= 0.041 and 0.020). The inactive state of c-Src, p-Tyr527-c-Src, was decreased in male patients but increased HCV-infected patients (P= 0.044 and 0.033). The Kaplan-Meier survival curve further showed that increased p-Tyr416-c-Src and decreased non-p-Tyr527-c-Src expression were associated with a poor patient survival rate (P= 0.004 and 0.025). Interestingly, the expression of non-p-Tyr416-c-Src was positively correlated with that of p-Tyr527-c-Src in the HCC lesions (P= 0.040). In addition, the patients with concomitantly low p-Tyr416-c-Src and non-p-Tyr527-c-Src expression had a prolonged overall survival rate (P= 0.030). A multivariable COX regression model showed that p-Tyr416-c-Src expression was an effective predictor for patient survival in HCC [OR = 3.78, 95%CI = 1.46–9.76;P= 0.006]. Our results suggest that the active state of c-Src, p-Tyr416-c-Src, may serve as an independent prognostic marker of patient survival in HCC. Relative levels of other phosphorylated or non-phosphorylated c-Src kinases may also present different statuses during HCC development and require further investigation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shuaiqun Wang ◽  
Dalu Yang ◽  
Wei Kong

The autophagy cell, which can inhibit the formation of tumor in the early stage and can promote the development of tumor in the late stage, plays an important role in the development of tumor. Therefore, it has potential significance to explore the influence of autophagy-related genes (AAGs) on the prognosis of hepatocellular carcinoma (HCC). The differentially expressed AAGs are selected from HCC gene expression profile data and clinical data downloaded from the TCGA database, and human autophagy database (HADB). The role of AAGs in HCC is elucidated by GO functional annotation and KEGG pathway enrichment analysis. Combining with clinical data, we selected age, gender, grade, stage, T state, M state, and N state as Cox model indexes to construct the multivariate Cox model and survival curve of Kaplan Meier (KM) was drawn to estimate patients’ survival between high- and low-risk groups. Through an ROC curve drawn by univariate and multivariate Cox regression analysis, we found that seven genes with high expression levels, including HSP90AB1, SQSTM1, RHEB, HDAC1, ATIC, HSPB8, and BIRC5 were associated with poor prognosis of HCC patients. Then the ICGC database is used to verify the reliability and robustness of the model. Therefore, the prognosis model of HCC constructed by autophagy genes might effectively predict the overall survival rate and help to find the best personalized targeted therapy of patients with HCC, which can provide better prognosis for patients.


2017 ◽  
Vol 28 ◽  
pp. x75
Author(s):  
K. Waren ◽  
A.D. Vatvani ◽  
D. Widjaja ◽  
M. Leonardo ◽  
I D G K Thobias Adiya ◽  
...  

2017 ◽  
Vol 9 (10) ◽  
pp. 615-626 ◽  
Author(s):  
Sung Won Lee ◽  
Hae Lim Lee ◽  
Nam Ik Han ◽  
Jung Hyun Kwon ◽  
Soon Woo Nam ◽  
...  

Background: More than one-third of hepatocellular carcinoma (HCC) patients are diagnosed at advanced stage with portal vein tumor thrombosis (PVTT) or extrahepatic metastasis. However, the outcomes of current therapeutic approaches are unsatisfactory. As a novel therapeutic strategy for unresectable HCC with PVTT, we analyzed the outcomes of transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil (TAC-ECF) and compared its therapeutic effects and toxicity with transarterial chemoembolization (TACE) using doxorubicin (DOX). Methods: A total of 540 consecutive HCC patients who received TACE at the Catholic Medical Center between January 2007 and November 2013 were enrolled. Of these patients, we retrospectively analyzed 129 Barcelona clinic liver cancer stage C HCC patients with PVTT who received either TAC-ECF or TACE using DOX. Results: The objective tumor response rate was higher in the TAC-ECF group, with 31.3% objective response rate after TAC-ECF compared to 10% after DOX treatment ( p = 0.004). Median follow-up period was 7 months (range, 1–57 months). The overall survival rate was also significantly higher in the TAC-ECF group compared to the DOX group (median 9.3 versus 4.6 months, p < 0.0001). Multivariate analysis revealed that TAC-ECF and extrahepatic metastasis were independent predictive factors for overall survival ( p < 0.0001 and p = 0.002 respectively). No serious adverse effects developed in both groups. Conclusions: TAC-ECF therapy was tolerable and showed higher overall survival rate and tumor response compared to the conventional TACE DOX in advanced stage HCC patients with PVTT. Therefore, TAC-ECF may be considered as an effective treatment option for patients with unresectable HCC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shuying Chen ◽  
Zile Fu ◽  
Shuzhan Wen ◽  
Xiaoyi Yang ◽  
Chengxuan Yu ◽  
...  

ObjectiveSerum microRNAs (miRNAs) may serve as biomarkers in various cancers. Our study aims to explore the roles of miR-497 and miR-1246 in hepatocellular carcinoma (HCC).MethodsThe expression levels of miR-497 and miR-1246 were measured by RT-PCR. A correlation analysis was conducted between the expression levels of miR-497 and miR-1246 and clinicopathological characteristics of patients. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic efficacy in HCC. In addition, bioinformatics tools were also utilized to predict the potential targets of miR-497 and miR-1246.ResultsThe expression level of miR-497 in HCC was significantly down-regulated compared with the control group while the miR-1246 revealed a significantly higher expression level in HCC. There was a significant correlation demonstrated between the expression levels of miR-497 and miR-1246 in preoperative serum of HCC and the differentiation degree, Tumor Node Metastasis (TNM) classification, and metastasis. The expression levels of serum miR-497 and miR-1246 were significantly associated with the diagnosis, prognosis, and overall survival rate of patients with HCC. Moreover, the potential target genes of miR-497 in HCC include ARL2, UBE2Q1, PHF19, APLN, CHEK1, CASK, SUCO, CCNE1, and KIF23. The low expression of these nine genes is associated with a better prognosis of HCC patients. AUTS2 is a novel target gene of miR-1246, and its low expression is significantly related to the low overall survival rate of HCC patients.ConclusionsmiR-497 and miR-1246 are possibly involved in the progression of HCC by regulating target genes, respectively, and could serve as biomarkers in HCC.


PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0171269 ◽  
Author(s):  
Chun-San Tai ◽  
Yan-Ren Lin ◽  
Tsung-Han Teng ◽  
Ping-Yi Lin ◽  
Siang-Jyun Tu ◽  
...  

Medicina ◽  
2019 ◽  
Vol 55 (12) ◽  
pp. 780
Author(s):  
Angel Yordanov ◽  
Martin Karamanliev ◽  
Milena Karcheva ◽  
Assia Konsoulova ◽  
Mariela Vasileva-Slaveva ◽  
...  

Background and objectives: Lymphoepithelioma-like carcinoma (LELC) is a histological type of malignant tumor arising from the uncontrolled mitosis of transformed cells originating in epithelial tissue. It is a rare subtype of squamous cell carcinoma of the uterine cervix. There are significant differences in frequency, mean age, viral status, and outcomes in Asian or Caucasian patients. Materials and Methods: A retrospective study of all cases of lymphoepithelioma-like carcinoma of the cervix at the Clinic of Oncogynecology, University Hospital, Pleven, Bulgaria between 1 January 2007 and 31 December 2016 was performed. All patients were followed-up till March 2019. We analyzed some clinical characteristics of the patients, calculated the frequency of lymphoepithelioma-like carcinoma of the cervix from all patients with stage I cervical cancer, and looked at the overall survival rate, the 5-year survival rate, and the correlation between overall survival, lymph node status, and the size of the tumor. Results: The frequency of lymphoepithelioma-like carcinoma was 3.3% for all cases with cervical carcinoma at stage I. The mean age of the patients with LELC was 49.6 years (range 32–67). Fourteen patients (82.4%) were in the FIGO IB1 stage, three patients (17.6%) were in the FIGO IB2 stage. Lymph nodes were metastatic in three patients (17.6%), non-metastatic in 13 patients (76.5%), and unknown in one patient. The overall survival rate was 76.47% for the study period and the 5-year survival rate of the patients that were followed-up until the 5th year (14 patients) was 69.23%. Conclusions: Lymphoepithelioma-like carcinoma is a rare SCC subtype, but it could be more frequent among western patients than previously thought. Our results do not confirm the data showing low risk of lymph metastasis and good prognosis of LELC, which is why we think that the treatment in these cases has to be more aggressive than is reported in the literature.


2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110294
Author(s):  
Jihan Wang ◽  
Yangyang Wang ◽  
Jing Xu ◽  
Qiying Song ◽  
Jingbo Shangguan ◽  
...  

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The landscape of HCC’s molecular alteration signature has been explored over the last few decades. Even so, more comprehensive research is still needed to improve understanding of tumorigenesis and progression of HCC, as well as to identify potential biomarkers for the malignancy. In this research, a comprehensive bioinformatics analysis was conducted based on the publicly available databases from both the Cancer Genome Atlas (TCGA) program and the gene expression omnibus (GEO) database. R/Bioconductor was used to analyze differentially expressed genes (DEGs) between HCC tumor and normal control (NC) samples, and then a protein-protein interaction (PPI) network of DEGs was established through the STRING platform. Finally, the application of specific candidate genes as diagnostic or prognostic biomarkers of HCC was explored and evaluated by ROC and survival analysis. A total of 310 DEGs were detected in the HCC tumor samples. Thirty-six hub DEGs in the PPI network and 10 candidates of the 36 genes showed significant alterations in tumor expression, including CDKN3, TOP2A, UBE2C, CDC20, PBK, ASPM, KIF20A, NCAPG, CCNB2, CYP3A4. The 10-gene signature had relatively significant effects when distinguishing tumors from normal samples (sensitivity >70%, specificity >70%, AUC >0.8, p <  0.001). Eight candidate genes were negatively correlated with the overall survival rate of the patients ( p <  0.05) and were all up-regulated in HCC tumor samples. The age and gender factors had no significant impact on the overall survival rate of HCC patients ( p >  0.05), and the TNM stage status factor had a significant negative prognosis correlation ( p <  0.05). This research provides evidence for a better understanding of tumorigenesis and progression of HCC and helps to explore candidate targets for disease diagnosis and treatment.


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