CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis in hepatocellular carcinoma

Zheng, Hao; Jiang, Weihua; Tian, Tian V.; Tan, Haisong; Chen, Ying; Qiao, Guanglei; Han, Jun; Huang, Shengyu; Yang, Yuan; Li, Shuai; Wang, Zhenguang; Gao, Rong; Ren, Hao; Xing, Hao; Ni, Jingwei; Wang, Linhui; Ma, Lijun; Zhou, Weiping

doi:10.18632/oncotarget.14770

Cited by 42 publications

(33 citation statements)

References 43 publications

(34 reference statements)

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“…Overexpression of VCAN may have a role in initiation and progression of gastric cancer since changes were observed between normal and pathological stages and between each stage. VCAN may play an oncogenic role in gastric cancer, promoting disease progression from early to advance stage in accordance with several reports linking upregulated gene expressions with carcinogenesis and disease progression (34)(35)(36)(37)(38)(39)(40). Immunohistochemical examination of VCAN expression also confirmed our findings, with a higher protein expression in cancer tissues than normal tissues.…”

Section: Discussionsupporting

confidence: 89%

VCAN – A novel prognostic marker for gastric cancer

Binang

Wang

Tewara³

et al. 2019

Preprint

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Background Versican (VCAN) is a large aggregating extracellular matrix proteoglycan implicated in the pathogenesis of most human cancers but its role in gastric cancer is not yet elucidated. We designed the present study to investigate the expression, prognostic value, relationship between genetic alterations and patient’s outcome, disease associations, as well as genetic and protein interactions of VCAN in gastric cancer. Methods Expression of VCAN in tumor and normal tissues was studied with ONCOMINE, UALCAN, and GEPIA databases and the human protein atlas. UALCAN, GEPIA, OncoLnc and Kaplan-Meier plotter were used to assess the prognostic values of VCAN in gastric cancer. Subgroup analysis of the clinical significance of VCAN in gastric cancer was done using Kaplan-Meier plotter. Genetic alterations of VCAN and their associations with patient’s outcome were studied with cBioPortal. Open targets platform was used to study diseases associated with VCAN, GeneMANIA was used to obtain the neighbor genes interaction network of VCAN, and STRING was used to examine VCAN interaction with other proteins. Results VCAN was upregulated and associated with clinical cancer stages. High VCAN expression predicted unfavorable outcome for all patients; subgroup analysis showed worse outcomes for patients treated with surgery or other adjuvants (other than 5-FU based adjuvant) but better outcome for patients treated with 5-FU based adjuvant, associating VCAN expression with chemosensitivity to 5-FU based adjuvants, but chemoresistance to other adjuvants. Genetic alteration of VCAN correlated with a favorable outcome in terms of disease-free survival for patients. Also, open targets platform showed that VCAN is associated with gastric cancer and is a potential therapeutic target for the disease. Finally, interaction of VCAN with neighbor genes and proteins revealed that VCAN interacts with genes and proteins that drive tumorigenesis and cancer progression. Conclusion The results of this study show that VCAN is an oncogene in gastric cancer whose expression can be applied as a biomarker for prognostic prediction, selection of appropriate chemotherapy drugs/monitoring of treatment response, and is a potential therapeutic target for gastric cancer.

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Section: Discussionsupporting

confidence: 89%

VCAN – A novel prognostic marker for gastric cancer

Binang

Wang

Tewara³

et al. 2019

Preprint

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“…Previously, several groups have shown that aberrant CBX member expression were observed in certain cancers tissues [ 27 – 29 ]. CBX1 levels were prominent in prostate cancer [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic values of distinct CBX family members in breast cancer

et al. 2017

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Chromobox (CBX) family proteins are canonical components in polycomb repressive complexes 1 (PRC1), with epigenetic regulatory function and transcriptionally repressing target genes via chromatin modification. A plethora of studies have highlighted the function specifications among CBX family members in various cancer, including lung cancer, colon cancer and breast cancer. Nevertheless, the functions and prognostic roles of distinct CBX family members in breast cancer (BC) remain elusive. In this study, we reported the prognostic values of CBX family members in patients with BC through analysis of a series of databases, including CCLE, ONCOMINE, Xena Public Data Hubs, and Kaplan-Meier plotter. It was found that the mRNA expression of CBX family members were noticeably higher in BC than normal counterparts. CBX2 was highly expressed in Basal-like and HER-2 subtypes, while CBX4 and CBX7 expressions were enriched in Luminal A and Luminal B subtypes of BC. Survival analysis revealed that CBX1, CBX2 and CBX3 mRNA high expression was correlated to worsen relapse-free survival (RFS) for all BC patients, while CBX4, CBX5, CBX6 and CBX7 high expression was correlated to better RFS in this setting. Noteworthily, CBX1 and CBX2 were associated with chemoresistance whereas CBX7 was associated with tamoxifen sensitivity, as well as chemosensitivity in breast tumors. Therefore, we propose that CBX1, CBX2 and CBX7 are potential targets for BC treatment. The results might be beneficial for better understanding the complexity and heterogeneity in the molecular underpinning of BC, and to develop tools to more accurately predict the prognosis of patients with BC.

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“…However, several studies have shown that CBX6 preferentially associates with non-PRC proteins and thus questioned the role of CBX6 as canonical PRC1 component [ 35 , 36 ]. In hepatocellular carcinoma CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis [ 37 ]. Thus, it will be interesting to continue the analysis of CBX6 in MDS although its role might not be related to PRC1 function.…”

Section: Discussionmentioning

confidence: 99%

Polycomb protein RING1A limits hematopoietic differentiation in myelodysplastic syndromes

et al. 2017

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Genetic lesions affecting epigenetic regulators are frequent in myelodysplastic syndromes (MDS). Polycomb proteins are key epigenetic regulators of differentiation and stemness that act as two multimeric complexes termed polycomb repressive complexes 1 and 2, PRC1 and PRC2, respectively. While components and regulators of PRC2 such as ASXL1 and EZH2 are frequently mutated in MDS and AML, little is known about the role of PRC1.To analyze the role of PRC1, we have taken a functional approach testing PRC1 components in loss- and gain-of-function experiments that we found overexpressed in advanced MDS patients or dynamically expressed during normal hematopoiesis.This approach allowed us to identify the enzymatically active component RING1A as the key PRC1 component in hematopoietic stem cells and MDS. Specifically, we found that RING1A is expressed in CD34+ bone marrow progenitor cells and further overexpressed in high-risk MDS patients. Knockdown of RING1A in an MDS-derived AML cell line facilitated spontaneous and retinoic acid-induced differentiation. Similarly, inactivation of RING1A in primary CD34+ cells augmented erythroid differentiation. Treatment with a small compound RING1 inhibitor reduced the colony forming capacity of CD34+ cells from MDS patients and healthy controls. In MDS patients higher RING1A expression associated with an increased number of dysplastic lineages and blasts. Our data suggests that RING1A is deregulated in MDS and plays a role in the erythroid development defect.

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CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis in hepatocellular carcinoma

Cited by 42 publications

References 43 publications

VCAN – A novel prognostic marker for gastric cancer

VCAN – A novel prognostic marker for gastric cancer

Prognostic values of distinct CBX family members in breast cancer

Polycomb protein RING1A limits hematopoietic differentiation in myelodysplastic syndromes

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