Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy

Yokoi, Keigo; Harada, Hiroki; Yokota, Kazuko; Ishii, Satoru; Tanaka, Toshimichi; Nishizawa, Nobuyuki; Shimazu, Masashi; Kojo, Ken; Miura, Hirohisa; Yamanashi, Takahiro; Sato, Takeo; Nakamura, Takatoshi; Watanabe, Masahiko; Yamashita, Keishi

doi:10.1245/s10434-018-6865-z

Cited by 15 publications

(14 citation statements)

References 20 publications

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“…Interestingly, assessing the methylation status of specific genes could be useful in clinical practice. Indeed, it could represent a biomarker for the detection or monitoring of specific diseases such as CRC, and more particularly of the serrated lesions that are associated with a CIMP signature [58,59,60]. For instance, a recent study reported on a positive correlation between CIMP and older age in SSA/Ps, indicating a lower risk of developing a malignancy in young patients [61].…”

Section: Cpg Island Methylator Phenotype An Epigenetic Signature mentioning

confidence: 99%

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

Palma

D’Argenio

Pol

et al. 2019

Cancers

140

102

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Colorectal cancer (CRC) is a leading cause of cancer death worldwide. It includes different subtypes that differ in their clinical and prognostic features. In the past decade, in addition to the conventional adenoma-carcinoma model, an alternative multistep mechanism of carcinogenesis, namely the “serrated pathway”, has been described. Approximately, 15 to 30% of all CRCs arise from neoplastic serrated polyps, a heterogeneous group of lesions that are histologically classified into three morphologic categories: hyperplastic polyps, sessile serrated adenomas/polyps, and the traditional serrated adenomas/polyps. Serrated polyps are characterized by genetic (BRAF or KRAS mutations) and epigenetic (CpG island methylator phenotype (CIMP)) alterations that cooperate to initiate and drive malignant transformation from normal colon mucosa to polyps, and then to CRC. The high heterogeneity of the serrated lesions renders their diagnostic and pathological interpretation difficult. Hence, novel genetic and epigenetic biomarkers are required for better classification and management of CRCs. To date, several molecular alterations have been associated with the serrated polyp-CRC sequence. In addition, the gut microbiota is emerging as a contributor to/modulator of the serrated pathway. This review summarizes the state of the art of the genetic, epigenetic and microbiota signatures associated with serrated CRCs, together with their clinical implications.

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Section: Cpg Island Methylator Phenotype An Epigenetic Signature mentioning

confidence: 99%

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

Palma

D’Argenio

Pol

et al. 2019

Cancers

140

102

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“… 8 Moreover, the methylation of the CDO1’s promoter region was reported in many types of cancer, especially in the stomach, esophagus, and colon cancer. 7 , 12 , 13 The interaction between the 2 genes and the immunocytes in breast cancer’s Tumor Micro-Environment (TME) is rarely examined systemically.…”

Section: Introductionmentioning

confidence: 99%

A BIRC5^High COD1^Low Cancer Tissue Phenotype Indicates Poorer Prognosis of Metastatic Breast Cancer Patients

Bai

Yuan

et al. 2022

Cancer Inform

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Extensive data research is helpful to find sensitive biomarkers for prognostic prediction of metastatic breast cancer. Through analyzing multiple GEO datasets, literature retrieval, and verified in GEPIA datasets, we identify BIRC5 (Baculoviral IAP repeat containing 5) and CDO1 (Cysteine dioxygenase type 1) as DEGs (differentially expressed genes) between breast tumor and normal tissue and DEGs between metastatic breast cancer and breast cancer in situ. Then, we performed a series of in silico studies on BIRC5 and CDO1 using online tools including the UALCAN, TIMER, TCGA-BRCA, LinkedOmics Kaplan-Meier Plotter, and an R script for analysis. To verify the association of 2 genes expression and patients’ clinical data, we detected BIRC5 and CDO1 mRNA in the tissue of 48 breast cancer patients. The results showed the tumor with BIRC5high CDO1low expression generally indicated patients’ shorter overall (OS) and relapse-free survival (RFS). Specifically, BIRC5 and CDO1 levels significantly affect OS or RFS in patients with Lymph node metastasis and molecular subtypes of TNBC (triple-negative breast cancer) and Luminal A. A BIRC5high tumor displayed a purer tumor purity and expressed more KIR receptors on NK cells while activating more FOXP3+CD25+ Treg cells. The CDO1low tumors infiltrated with more immunocytes leading to less tumor purity. In our verified experiment, BIRC5 mRNA level in patients with stage III and over was significantly higher than in patients with stage 0 to II, but there were no significant differences among molecular subtyping groups; TNBC tissue expressed lower CDO1 mRNA level than HER2+ and Luminal type cancer tissue. In conclusion, a BIRC5high CDO1low expression type in breast cancer tissue indicates a poorer prognosis of patients. The potential mechanism might be increased BIRC5 expression in cancer tissue is likely to accompany NK cells inhibition, activating more Treg cells, and lacking effective CD8+ T cells proliferation. Meanwhile, CDO1 level is positively related to more immunocytes infiltration.

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“…Some studies were aimed to construct a prognosis model for predicting chemoresistance, but it has not been well established, since most previous relevant studies constructed their prognostic models using parameters from clinical baseline characteristics (such as blood sugar levels [4], body mass index [5] and age [6]) and single molecular biomarkers (CDO1 [7] and MASTL [8] ). Then, a thorough understanding of L-OHP and 5-FU mechanisms of action and interventions to overcome resistance are still relatively needed.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Six-Gene Signature Predicting Overall Survival for Oxaliplatin and 5-Fluorouracil Resistant Colon Cancer and Potential Drug-Repurposing

Yang¹,

Cai²,

Su³

et al. 2020

Preprint

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Background: Oxaliplatin (L-OHP) and 5-fluorouracil (5-FU) resistance in colorectal cancer (CRC) is a major medical problem. Therefore, detailed mechanisms and predictive markers are urgently needed. The aim of this study was to identify key pathways, a robust prognostic gene signature and potential drug-repurposing. Methods: In order to confirm the predictive markers and detailed molecular mechanisms of L-OHP and 5-Fu chemoresistant CRC, we performed weighted correlation network analysis (WGCNA), an unsupervised analysis method, to identify the chemoresistant CRC significantly related genes. Then, the gene prognostic model was conducted by Univariate Cox regression and Lasso penalized Cox regression analysis. Subsequently, the time-dependent receiver operating characteristic (ROC) and Kaplan-Meier survival curve were performed to assess the prognostic capacity of the model. Simultaneously, pathway enrichment was done to identify the key pathways involved in chemoresistant CRC. Moreover, we explored how the hub genes interacted with key pathways and transcription factors. Then, we found the potential drug target by the subcellular location fo hub genes. Finally, we identified the potential drug-repurposing by virtual screening for chemoresistant CRC according to ZINC 15 database. Results: We identified the key pathways using KEGG over-representation test and Gene Set Enrichment Analysis (GSEA): Ribosome KEGG pathway. Moreover, six hub-genes prognostic model was conducted by Univariate Cox regression and Lasso penalized Cox regression analysis. Additionally, the detailed interactions among the pathway and hub genes (RBM6, PNN, LEF1, ANO1, PAFAH1B3 and BHLHE41) were examined by protein-protein interaction (PPI) network and shortest-pathway analysis. Furthermore, ANO1 was considered the potential drug target based on the subcellular location and ZINC000018043251 was verified the potential drug by virtual screening Conclusions: Our study identified a novel six-gene resistant signature for CRC prognosis prediction and the molecular details of these interactions between hub genes (RBM6, PNN, LEF1, ANO1, PAFAH1B3 and BHLHE41) and Ribosome key pathways. Furthermore, ZINC000018043251 was verified the potential drug for ANO1 by virtual screening, which might help to improve the outcome of CRC patients.

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Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy

Cited by 15 publications

References 20 publications

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

A BIRC5^High COD1^Low Cancer Tissue Phenotype Indicates Poorer Prognosis of Metastatic Breast Cancer Patients

Identification of a Six-Gene Signature Predicting Overall Survival for Oxaliplatin and 5-Fluorouracil Resistant Colon Cancer and Potential Drug-Repurposing

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Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy

Cited by 15 publications

References 20 publications

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

A BIRC5High COD1Low Cancer Tissue Phenotype Indicates Poorer Prognosis of Metastatic Breast Cancer Patients

Identification of a Six-Gene Signature Predicting Overall Survival for Oxaliplatin and 5-Fluorouracil Resistant Colon Cancer and Potential Drug-Repurposing

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A BIRC5^High COD1^Low Cancer Tissue Phenotype Indicates Poorer Prognosis of Metastatic Breast Cancer Patients