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23. Comprehensive analysis of the clinical significance, immune infiltration, and biological role of MARCH ligases in HCC

Author

Cao, Jun, Tu, Dao-yuan, Zhou, Jie, Jiang, Guo-qing, Jin, Sheng-jie, Su, Bing-bing, Tang, Hao, Tang, Yu-hong, Wang, Ao-qing, Wang, Qian, Liu, Ren-jie, Zhang, Chi, and Bai, Dou-sheng

Subjects
Minor Histocompatibility Antigens, Amino Acid Transport System ASC, Carcinoma, Hepatocellular, Aryldialkylphosphatase, Ubiquitin-Protein Ligases, Liver Neoplasms, Immunology, Tumor Microenvironment, Humans, Immunology and Allergy, Chemoembolization, Therapeutic, Ubiquitins, Cytochrome P-450 CYP2C9
Abstract

The membrane‐associated RING‐CH (MARCH) family, a member of the E3 ubiquitin ligases, has been confirmed by a growing number of studies to be associated with immune function and has been highlighted as a potential immunotherapy target. In our research, hepatocellular carcinoma (HCC) patients were divided into C1 and C2 MARCH ligase-related patterns by the non-negative matrix factorization (NMF) algorithm. Multiple analyses revealed that the MARCH ligase-related cluster was related to prognosis, clinicopathological characteristics, and the tumor immune microenvironment (TIME). Next, the signature (risk score) of the MARCH prognosis was constructed, including eight genes associated with the MARCH ligase (CYP2C9, G6PD, SLC1A5, SPP1, ANXA10, CDC20, PON1, and FTCD). The risk score showed accuracy and stability. We found that the correlations between risk score and TIME, tumor mutation burden (TMB), prognosis, and clinicopathological characteristics were significant. Additionally, the risk score also had important guiding significance for HCC treatment, including chemotherapy, immunotherapy, and transarterial chemoembolization (TACE).

Published
2022

33. RNF128 Promotes Malignant Behaviors via EGFR/MEK/ERK Pathway in Hepatocellular Carcinoma

Author

Bai, Xue-Song, Zhang, Chi, Peng, Rui, Jiang, Guo-Qing, Jin, Sheng-Jie, Wang, Qian, Ke, Ai-Wu, and Bai, Dou-Sheng

Subjects
RNF128, EGFR/MEK/ERK signaling pathway, hepatocellular carcinoma, prognosis, ubiquitination, neoplasms, digestive system diseases, OncoTargets and Therapy, Original Research
Abstract

Xue-Song Bai,1,* Chi Zhang,2,* Rui Peng,2,* Guo-Qing Jiang,2 Sheng-Jie Jin,2 Qian Wang,2 Ai-Wu Ke,3 Dou-Sheng Bai2 1The First Clinical Medical College, Dalian Medical University, Dalian, Liaoning 116044, People’s Republic of China; 2Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225009, Jiangsu, People’s Republic of China; 3Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dou-Sheng BaiClinical Medical College, Yangzhou University, 98 West Nantong Road, Yangzhou, Jiangsu 225000, People’s Republic of ChinaTel +86-514-87373385Fax +86-514-87990188Email drbaidousheng@163.comBackground: The ubiquitin-proteasome system participates in the pathogenesis and progression of hepatocellular carcinoma (HCC). As an E3 ubiquitin ligase, RNF128 has been proved vital in carcinogenesis, whereas, little is known about the oncogenic mechanisms of RNF128 in HCC.Materials and Methods: Through tissue microarray from HCC patients, we analyzed RNF128 expression and its relationship with clinical outcomes in HCC. Western blot and quantitativerealtime polymerase chain reaction (qRT-PCR) were performed to examine expression levels of RNF128 in HCC tissues and cell lines. Effects of RNF128 on HCC cellular biological functions and the potential mechanism were evaluated through knockdown and overexpression assays in vitro and in vivo methods.Results: RNF128 expression was found to be remarkably elevated in HCC tissues compared with adjacent normal tissues. Furthermore, the overexpression of RNF128 enhanced hepatoma cells proliferation, colony formation, migration, invasion, and apoptotic resistance both in vitro and in vivo. Mechanistically, RNF128 activated EGFR/MEK/ERK signaling pathway and the EGFR inhibitor, gefitinib partially reversed RNF128-enhanced proliferation, invasion, and migration in hepatoma cells.Conclusion: RNF128 promotes HCC progression by activating EGFR/MEK/ERK signaling pathway, which might function as a novel prognostic molecular signature with the potential to be a candidate therapeutic target for HCC patients.Keywords: hepatocellular carcinoma, RNF128, ubiquitination, EGFR/MEK/ERK signaling pathway, prognosis

Published
2020

34. RNF128 Promotes Malignant Behaviors via EGFR/MEK/ERK Pathway in Hepatocellular Carcinoma

Author

Bai,Xue-Song, Zhang,Chi, Peng,Rui, Jiang,Guo-Qing, Jin,Sheng-Jie, Wang,Qian, Ke,Ai-Wu, Bai,Dou-Sheng, Bai,Xue-Song, Zhang,Chi, Peng,Rui, Jiang,Guo-Qing, Jin,Sheng-Jie, Wang,Qian, Ke,Ai-Wu, and Bai,Dou-Sheng

Abstract

Xue-Song Bai,1,* Chi Zhang,2,* Rui Peng,2,* Guo-Qing Jiang,2 Sheng-Jie Jin,2 Qian Wang,2 Ai-Wu Ke,3 Dou-Sheng Bai2 1The First Clinical Medical College, Dalian Medical University, Dalian, Liaoning 116044, People’s Republic of China; 2Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225009, Jiangsu, People’s Republic of China; 3Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dou-Sheng BaiClinical Medical College, Yangzhou University, 98 West Nantong Road, Yangzhou, Jiangsu 225000, People’s Republic of ChinaTel +86-514-87373385Fax +86-514-87990188Email drbaidousheng@163.comBackground: The ubiquitin-proteasome system participates in the pathogenesis and progression of hepatocellular carcinoma (HCC). As an E3 ubiquitin ligase, RNF128 has been proved vital in carcinogenesis, whereas, little is known about the oncogenic mechanisms of RNF128 in HCC.Materials and Methods: Through tissue microarray from HCC patients, we analyzed RNF128 expression and its relationship with clinical outcomes in HCC. Western blot and quantitative realtime polymerase chain reaction (qRT-PCR) were performed to examine expression levels of RNF128 in HCC tissues and cell lines. Effects of RNF128 on HCC cellular biological functions and the potential mechanism were evaluated through knockdown and overexpression assays in vitro and in vivo methods.Results: RNF128 expression was found to be remarkably elevated in HCC tissues compared with adjacent normal tissues. Furthermore, the overexpression of RNF128 enhanced hepatoma cells proliferation, colony formation, migration, invasion, and apoptotic resistance both in vitro and in vivo. Mechanistically, RNF128 activated EGFR/MEK/ERK signaling pathway and the EGFR inhibitor, gefitinib partially reversed RNF128-enhanced proliferation, invasion, and m

Published
2020

46. A practical nomogram and risk stratification system predicting the cancer‐specific survival for patients with early hepatocellular carcinoma.

Author

Yan, Bing, Su, Bing‐Bing, Bai, Dou‐Sheng, Qian, Jian‐Jun, Zhang, Chi, Jin, Sheng‐Jie, and Jiang, Guo‐Qing

Subjects
NOMOGRAPHY (Mathematics), RECEIVER operating characteristic curves, DECISION making
Abstract

Background: Our purpose was to establish and validate a nomogram model in early hepatocellular carcinoma (HCC) patients for predicting the cancer‐specific survival (CSS). Methods: We extracted eligible data of relevant patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Further, we divided all patients into two groups (training and validation cohorts) at random (7:3). Nomogram was established using effective risk factors based on univariate and multivariate analysis. The effective performance of nomogram was evaluated using concordance index (C‐index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic curve (ROC). Results: We selected 3620 patients with early HCC including the training cohort (70%, 2536) and the validation cohort (30%, 1084). The nomogram‐related C‐indexes were 0.755 (95% CI: 0.739–0.771) and 0.737 (95% CI: 0.712–0.762), in the training and validation cohorts, respectively. The calibration plots showed good consistency of 3‐and 5‐year CSS between the actual observation and the nomogram prediction. The 3‐, 5‐year DCA curves also indicated that the nomogram has excellent clinical utility. The 3‐, 5‐year area under curve (AUC) of ROC in the training cohort were 0.783, 0.779, respectively, and 0.767, 0.766 in the validation cohort, respectively. With the establishment of nomogram, a risk stratification system was also established that could divide all patients into three risk groups, and the CSS in different groups (i.e., low risk, intermediate risk, and high risk) had a good regional division. Conclusions: We developed a practical nomogram in early HCC patients for predicting the CSS, and a risk stratification system follow arisen, which provided an applicable tool for clinical management. [ABSTRACT FROM AUTHOR]

Published
2021
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