EGFR and SYNE2 are associated with p21 expression and SYNE2 variants predict post-operative clinical outcomes in HBV-related hepatocellular carcinoma

Han, Chuangye; Liao, Xiwen; Liu, Yu; Liu, Xiaoguang; Chen, Gang; Liu, Zhengtao; Lu, Sicong; Chen, Zhiwei; Su, Hao; Zhu, Guangzhi; Lu, Zili; Liu, Zhiming; Qin, Xue; Ying, Gui Shuang; Mo, Zengnan; Li, Le‐Qun; Peng, Tao

doi:10.1038/srep31237

Cited by 20 publications

(22 citation statements)

References 71 publications

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“…Immunohistochemical staining for MKI67 and p53 was performed on all samples by eligible full-time pathologists from aforementioned subjects according to previous criteria [24, 25]. To measure the MKI67 labeling index, up to 10 randomly selected ×40 high-power fields were analyzed when at least 1000 tumor cells were counted.…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China

Yang¹,

Yu²,

Han³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Hepatocellular carcinoma (HCC) is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of proliferation Ki-67 (MKI67) is used to assess proliferation activity of HCC The regulation of MKI67 expression remains unclear in HCC This study aims to explore the association between MKI67 expression and gene variants. Methods: A total of 195 hepatitis B virus (HBV)-related HCC patients were genotyped using Illumina HumanExome BeadChip-12-1_A (242,901 markers). An independent cohort (97 subjects) validated the association of polymorphism determinants and candidate genes with MKI67 expression. The relationships between MKI67 with p53 and variants of candidate genes in the clinical outcomes of HCC patients were analyzed. Results: We found that MKI67 combined with p53 was associated with a 3-year recurrence-free survival and five variants near TTN and CCDC8 were associated with MKI67 expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable outcome for HCC patients. Conclusion: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients.

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Section: Methodsmentioning

confidence: 99%

Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China

Yang¹,

Yu²,

Han³

et al. 2017

Cell Physiol Biochem

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“…Sorafenib as an anticancer drug is transported into the cell through SLC proteins (e.g., OCT1). Inside the cell, the drug is broken-down via phase 1 cytochrome P450 3A4 (CYP3A4) and phase 2 UDP glucuronosyltransferase 1A9 (UGT1A9) mediated metabolism to form the M1-M8 metabolites [84]. Sorafenib glucuronide (SG) is excreted out of the cell by a process mediated by ABC transporters.…”

Section: Discussionmentioning

confidence: 99%

“…The extent of sorafenib inhibition to the ERK phosphorylation (pERK) was significantly based on cell basal pERK expression level [83]. Variants of EGFR played an important role in p21 regulation and were associated with the clinical outcome of HBV-related HCC in a TP53-independent manner [84]. EGFR variants are reported to be correlated with drug sensitivity.…”

Section: Alteration Of Signaling Pathwaysmentioning

confidence: 99%

Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity

Cabral

Tiribelli

Sukowati

2020

Cancers

118

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Despite advances in biomedicine, the incidence and the mortality of hepatocellular carcinoma (HCC) remain high. The majority of HCC cases are diagnosed in later stages leading to the less than optimal outcome of the treatments. Molecular targeted therapy with sorafenib, a dual-target inhibitor targeting the serine-threonine kinase Raf and the tyrosine kinases VEGFR/PDGFR, is at present the main treatment for advanced-stage HCC, either in a single or combinatory regimen. However, it was observed in a large number of patients that its effectiveness is hampered by drug resistance. HCC is highly heterogeneous, within the tumor and among individuals, and this influences disease progression, classification, prognosis, and naturally cellular susceptibility to drug resistance. This review aims to provide an insight on how HCC heterogeneity influences the different primary mechanisms of chemoresistance against sorafenib including reduced drug intake, enhanced drug efflux, intracellular drug metabolism, alteration of molecular targets, activation/inactivation of signaling pathways, changes in the DNA repair machinery, and negative balance between apoptosis and survival of the cancer cells. The diverse variants, mutations, and polymorphisms in molecules and their association with drug response can be a helpful tool in treatment decision making. Accordingly, the existence of heterogeneous biomarkers in the tumor must be considered to strengthen multi-target strategies in patient-tailored treatment.

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“…Most of the HCC in China is hepatitis B virus (HBV)-related which is caused by the high HBV infection rates. 1 – 3 Although the overall survival of patients with HBV-related HCC had been improved, the survival still remains unsatisfactory. 4 , 5 Therefore, it is very important to find novel prognostic markers and potential therapeutic target for HBV-related HCC.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of increased expression of RACO-1 in patients with hepatitis B-related hepatocellular carcinoma

Chen

Liu

2017

TCRM

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RING domain AP-1 coactivator-1 (RACO-1) is a coactivator that links c-Jun to growth factor signaling and is essential for AP-1 function. This study aimed to investigate the expression and clinical significance of RACO-1 protein in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in China. A total of 136 tissue samples of HBV-related HCC were detected by immunohistochemistry (including 76 patients in training cohort and 60 patients in validation cohort). Correlation between RACO-1 expression and clinicopathologic features of HBV-related HCC was analyzed in both the cohorts. RACO-1 expression was significantly higher in HBV-related HCC tissues than in adjacent non-tumor liver tissues. All the patients were divided into two groups: the low expression group and the high expression group. RACO-1 expression was significantly related to vascular invasion (P=0.021), tumor numbers (P=0.046), International Union for Cancer Control/American Joint Committee on Cancer stage (P=0.006), cirrhosis (P=0.046), capsular (P=0.039), and Barcelona Clinic Liver Cancer stage (P=0.041) in training cohort. The validation cohort showed the same results. The high RACO-1 expression was the independent prognostic factor for HBV-related HCC patients in both training cohort and validation cohort. Our data implicate RACO-1 as a novel prognostic marker and a potential therapeutic target for HBV-related HCC.

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EGFR and SYNE2 are associated with p21 expression and SYNE2 variants predict post-operative clinical outcomes in HBV-related hepatocellular carcinoma

Cited by 20 publications

References 71 publications

Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China

Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China

Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity

Prognostic value of increased expression of RACO-1 in patients with hepatitis B-related hepatocellular carcinoma

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