Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility

Dooley, James; Lagou, Vasiliki; Goveia, Jermaine; Ulrich, Anna; Rohlenová, Kateřina; Heirman, Nathalie; Karakach, Tobias K.; Lampi, Yulia; Khan, Shawez; Wang, Jun; Dresselaers, Tom; Himmelreich, Uwe; Gunter, Marc J.; Prokopenko, Inga; Carmeliet, Peter; Liston, Adrian

doi:10.1016/j.celrep.2020.107880

Cited by 8 publications

(5 citation statements)

References 61 publications

(65 reference statements)

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“…Consistent with the literature, CDC20 was coexpressed with UBE2C in human clear cell renal cell carcinoma [24]. MAD2L1 is a vital component of the spindle assembly checkpoint and tends to be overexpressed in many cancer types [25][26][27]. It can therefore be assumed that the two molecules might be able to explain the involvement of UBE2C with cancer progression and invasion.…”

Section: Discussionsupporting

confidence: 82%

The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC

Sun

Zhi

et al. 2022

Cancers

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High-grade serous ovarian cancer (HGSOC) is the most fatal gynecological malignant tumor. DNA methylation is associated with the occurrence and development of a variety of tumor types, including HGSOC. However, the signatures regarding DNA methylation changes for HGSOC diagnosis and prognosis are less explored. Here, we screened differentially methylated genes and differentially expressed genes in HGSOC through the GEO database. We identified that UBE2C was hypomethylation and overexpression in ovarian cancer, which was associated with more advanced cancer stages and poor prognoses. Additionally, the pan-cancer analysis showed that UBE2C was overexpressed and hypomethylation in almost all cancer types and was related to poor prognoses for various cancers. Next, we established a risk or prognosis model related to UBE2C methylation sites and screened out the three sites (cg03969725, cg02838589, and cg00242976). Furthermore, we experimentally validated the overexpression of UBE2C in HGSOC clinical samples and ovarian cell lines using quantitative real-time PCR, Western blot, and immunohistochemistry. Importantly, we discovered that ovarian cancer cell lines had lower DNA methylation levels of UBE2C than IOSE-80 cells (normal ovarian epithelial cell line) by bisulfite sequencing PCR. Consistently, treatment with 5-Azacytidine (a methylation inhibitor) was able to restore the expression of UBE2C. Taken together, our study may help us to understand the underlying molecular mechanism of UBE2C in pan-cancer tumorigenesis; it may be a useful biomarker for diagnosis, treatment, and monitoring, not only of ovarian cancer but a variety of cancers.

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Section: Discussionsupporting

confidence: 82%

The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC

Sun

Zhi

et al. 2022

Cancers

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“…MAD2L1 can regulate the growth and apoptosis of colorectal cancer cells [ 58 ]. Dietary sugar increases the growth of pancreatic cancer cells by increasing MAD2L1 expression [ 59 ]. CCNB2, which is upregulated in colorectal cancer, may promote tumour cell growth by accelerating the cell cycle [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics prediction and experimental verification identify MAD2L1 and CCNB2 as diagnostic biomarkers of rhabdomyosarcoma

et al. 2021

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Background Rhabdomyosarcoma (RMS) is a malignant soft-tissue tumour. In recent years, the tumour microenvironment (TME) has been reported to be associated with the development of tumours. However, the relationship between the occurrence and development of RMS and TME is unclear. The purpose of this study is to identify potential tumor microenvironment-related biomarkers in rhabdomyosarcoma and analyze their molecular mechanisms, diagnostic and prognostic significance. Methods We first applied bioinformatics method to analyse the tumour samples of 125 patients with rhabdomyosarcoma (RMS) from the Gene Expression Omnibus database (GEO). Differential genes (DEGs) that significantly correlate with TME and the clinical staging of tumors were extracted. Immunohistochemistry (IHC) was applied to validate the expression of mitotic arrest deficient 2 like 1 (MAD2L1) and cyclin B2 (CCNB2) in RMS tissue. Then, we used cell function and molecular biology techniques to study the influence of MAD2L1 and CCNB2 expression levels on the progression of RMS. Results Bioinformatics results show that the RMS TME key genes were screened, and a TME-related tumour clinical staging model was constructed. The top 10 hub genes were screened through the establishment of a protein–protein interaction (PPI) network, and then Gene Expression Profiling Interactive Analysis (GEPIA) was conducted to measure the overall survival (OS) of the 10 hub genes in the sarcoma cases in The Cancer Genome Atlas (TCGA). Six DEGs of statistical significance were acquired. The relationship between these six differential genes and the clinical stage of RMS was analysed. Further analysis revealed that the OS of RMS patients with high expression of MAD2L1 and CCNB2 was worse and the expression of MAD2L1 and CCNB2 was related to the clinical stage of RMS patients. Gene set enrichment analysis (GSEA) revealed that the genes in MAD2L1 and CCNB2 groups with high expression were mainly related to the mechanism of tumour metastasis and recurrence. In the low-expression MAD2L1 and CCNB2 groups, the genes were enriched in the metabolic and immune pathways. Immunohistochemical results also confirmed that the expression levels of MAD2L1 (30/33, 87.5%) and CCNB2 (33/33, 100%) were remarkably higher in RMS group than in normal control group (0/11, 0%). Moreover, the expression of CCNB2 was related to tumour size. Downregulation of MAD2L1 and CCNB2 suppressed the growth, invasion, migration, and cell cycling of RMS cells and promoted their apoptosis. The CIBERSORT immune cell fraction analysis indicated that the expression levels of MAD2L1 and CCNB2 affected the immune status in the TME. Conclusions The expression levels of MAD2L1 and CCNB2 are potential indicators of TME status changes in RMS, which may help guide the prognosis of patients with RMS and the clinical staging of tumours.

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“…MAD2L1 can regulate the growth and apoptosis of colorectal cancer cells [41]. Dietary sugar increases the growth of pancreatic cancer cells by increasing MAD2L1 expression [42]. CCNB2, which is upregulated in colorectal cancer, may promote tumour cell growth by accelerating the cell cycle [43].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Prediction and Experimental Verification Identify MAD2L1 and CCNB2 as Diagnostic Biomarkers of Rhabdomyosarcoma

Xia

Meng

Zhao

et al. 2021

Preprint

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Background: Rhabdomyosarcoma (RMS) is a malignant soft-tissue tumour. In recent years, the tumour microenvironment (TME) has been reported to be associated with the development of tumours. However, the relationship between the occurrence and development of RMS and TME is unclear. The purpose of this study is to identify potential tumor microenvironment-related biomarkers in rhabdomyosarcoma and analyze their molecular mechanisms, diagnostic and prognostic significance.Methods: We first applied bioinformatics method to analyse the tumour samples of 187 patients with rhabdomyosarcoma (RMS) from the Gene Expression Omnibus database (GEO). Then, we used cell function and molecular biology techniques to study the progress of RMS.Results: Bioinformatics results show that the RMS TME key genes were screened, and a TME-related tumour clinical staging model was constructed. The top 10 hub genes were screened through the establishment of a protein-protein interaction network, and then Gene Expression Profiling Interactive Analysis was conducted to measure the overall survival (OS) of the 10 hub genes in the sarcoma cases in The Cancer Genome Atlas (TCGA). Six differential genes of statistical significance were acquired. The correlation between these six differential genes and the clinical stage of RMS was analysed. Our data found that the expression levels of MAD2L1 and CCNB2 negatively correlated with the OS of RMS patients and positively correlated with the clinical stage of RMS patients. Immunohistochemical results also confirmed that the expression levels of MAD2L1 (30/33, 87.5%) and CCNB2 (33/33, 100%) were remarkably higher in RMS group than in normal control group (0/11, 0%). Moreover, the expression of CCNB2 was related to tumour size. Further gene set enrichment analysis revealed that the genes in MAD2L1 and CCNB2 groups with high expression were mainly related to the mechanism of tumour metastasis and recurrence. In the low-expression MAD2L1 and CCNB2 groups, the genes were enriched in the metabolic and immune pathways. Downregulation of MAD2L1 and CCNB2 suppressed the growth, invasion, migration, and cell cycling of RMS cells and promoted their apoptosis. The CIBERSORT immune cell fraction analysis indicated that the expression levels of MAD2L1 and CCNB2 affected the immune status in the TME. Conclusions: The expression levels of MAD2L1 and CCNB2 may help guide the prognosis of patients with RMS and the clinical staging of tumours.

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Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility

Cited by 8 publications

References 61 publications

The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC

The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC

Bioinformatics prediction and experimental verification identify MAD2L1 and CCNB2 as diagnostic biomarkers of rhabdomyosarcoma

Bioinformatics Prediction and Experimental Verification Identify MAD2L1 and CCNB2 as Diagnostic Biomarkers of Rhabdomyosarcoma

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