scholarly journals Overexpression of Ubiquitin-Specific Protease15 (USP15) Promotes Tumor Growth and Inhibits Apoptosis and Correlated With Poor Disease-Free Survival in Hepatocellular Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382096745
Author(s):  
Xue-Qing Yao ◽  
Ling Li ◽  
Long-Zhen Piao ◽  
Guang-Jian Zhang ◽  
Xue-Zhu Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Profile ◽  
Regulatory Mechanism ◽  
Multivariate Analyses ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Free Survival ◽  
Cirrhotic Tissue ◽  
Primary Tissue ◽  
Disease Free

USP15 is a member of ubiquitin-specific proteases (USPs, the largest subfamily of deubiquitinases) and functions as a stabilize factor of target proteins in reversible ubiquitiantion progression. Dysregulated expression of USP15 has been observed in various cancers. However the expression profile and regulatory mechanism of USP15 in hepatocellular carcinoma (HCC) remains largely elusive. To exam the USP15 expression changes in the progression of HCC, we performed IHC analysis to test USP15 expression in a series of cancer-prone diseases including 2 normal liver tissues, 6 liver cirrhosis, 16 primary liver lesions and 15 metastases of hepatocellular carcinoma. The expression of USP15 was upregulated in various liver diseases in compared with normal tissue significantly (p < 0.05). Although no significant different of USP15 expression were discovered between cirrhotic tissue and primary tissue, its expression in HCC metastatic tissue was upregulated. Subsequently, we test the USP15 expression profile in a cohort of 66 HCC patients. USP15 expression was positively correlated with the recurrence of HCC significantly (p = 0.004). HCC patients with high USP15 expression had shorter disease free survival time in compare with those with low USP15 expression (56.9% VS 26.7%, P = 0.012). Subsequently, Cox multivariate analyses of clinical factors associated with disease free survival were performed and USP15 expression (p = 0.008) together with tumor size (p = 0.034) were proved to be independent predict factors in HCC. Then, we silenced USP15 expression in HCC cells and the results showed that downregulated USP15 expression resulting proliferation inhibition and apoptosis induction. In conclusion, our results suppose USP15 to be a potential target in HCC.

scholarly journals Comparison of Staging Systems of Hepatocellular Carcinoma

HPB Surgery ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Yongyut Sirivatanauksorn ◽  
Chutwichai Tovikkai
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Multivariate Analyses ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Patient Data ◽  
Free Survival ◽  
Staging Systems ◽  
Univariate Analyses ◽  
Disease Free

Many staging systems of hepatocellular carcinoma (HCC) were established; however, there is no consensus on which is proper in predicting prognosis. This study aims to evaluate various commonly used staging systems of HCC. Patients who underwent surgery during 2001–2007 were included. All patient data were retrospectively staged using six staging systems, that are American Joint Committee on Cancer (AJCC) Tumour-Node-Metastasis (TNM), Okuda staging, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), Chinese University Prognostic Index (CUPI), and Japan Integrated Staging (JIS). Child-Pugh classification was also evaluated. The staging systems were compared by mean of overall and disease-free survival. Total of 99 patient data were enrolled in the analyses. All staging systems except Okuda were significant in determining overall survival in univariate analyses. In multivariate analyses, TNM and Child-Pugh demonstrated better predictive power for overall survival. In terms of disease-free survival, univariate analyses revealed that TNM, CLIP, BCLC, CUPI, and JIS were significant, and TNM was the best predictive staging system in multivariate analyses. In our study, TNM and Child-Pugh are the representative systems in predicting survival of HCC patients who undergo surgical resection. Moreover, they are practical and easily assessable in clinical practice.

scholarly journals Evaluation of X-Ray Repair Cross-Complementing Family Members as Potential Biomarkers for Predicting Progression and Prognosis in Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Mei ◽  
Huiyu Wang ◽  
Runjie Wang ◽  
Jiadong Pan ◽  
Chaoying Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Characteristics ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Free Survival ◽  
X Ray ◽  
The Relationship ◽  
Disease Free ◽  
Potential Biomarkers

The X-ray repair cross-complementing (XRCC) gene family has been revealed to participate in the carcinogenesis and development of numerous cancers. However, the expression profiles and prognostic values of XRCCs (XRCC1-6) in hepatocellular carcinoma (HCC) have not been explored up to now. The transcriptional levels of XRCCs in primary HCC tissues were analyzed by UALCAN and GEPIA. The relationship between XRCCs expression and HCC clinical characteristics was evaluated using UALCAN. Moreover, the prognostic values of XRCCs expression and mutations in HCC patients were investigated via the GEPIA and cBioPortal, respectively. Last but not least, the functions and pathways of XRCCs in HCC were also predicted by cBioPortal and DVAID. The transcriptional levels of all XRCCs in HCC tissues were notably elevated compared with normal liver tissues. Meanwhile, upregulated XRCCs expression was positively associated with clinical stages and tumor grades of HCC patients. Survival analysis using the GEPIA database revealed that high transcription levels of XRCC2/3/4/5/6 were associated with lower overall survival (OS) and high transcription levels of XRCC1/2/3/6 were correlated with poor disease-free survival (DFS) in HCC patients. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated the possible mechanisms of XRCCs and their associated genes participating in the oncogenesis of HCC. Our findings systematically elucidate the expression profiles and distinct prognostic values of XRCCs in HCC, which might provide promising therapeutic targets and novel prognostic biomarkers for HCC patients.

scholarly journals Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chih-Wen Lin ◽  
Tsung-Chin Wu ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Pei-Min Hsieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Free Survival ◽  
Before And After ◽  
Disease Free

Abstract Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

scholarly journals Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2810
Author(s):  
Muhammad Yogi Pratama ◽  
Alessia Visintin ◽  
Lory Saveria Crocè ◽  
Claudio Tiribelli ◽  
Devis Pascut
Keyword(s):  
Hepatocellular Carcinoma ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Therapy Response ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Free Survival ◽  
Microarray Profiling ◽  
Disease Free ◽  
Arterial Chemoembolization

The clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD. The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p = 0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC.

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