Multi-Omics Analysis to Identify Driving Factors in Colorectal Cancer

Xu, Xi; Gong, Chaoju; Wang, Yunfeng; Hu, Yibing; Liu, Hong; Fang, Zejun

doi:10.2217/epi-2020-0073

Cited by 14 publications

(10 citation statements)

References 49 publications

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“…(40) A study by Xu et al identi ed that REP15 could serve as a novel prognostic gene for CRC and low expression of REP15 was associated with unfavorable prognosis of CRC, besides, they also found that the high expression of REP15 was positively correlated with the p53 pathway, and negatively correlated with glycerophospholipid metabolism, hedgehog and insulin pathways. (41) The gene B3GNT6 encodes a glycosyltransferase, which is capable of adding progressive carbohydrates to form a core 3 O-glycan structure and only appears in speci c tissues, such as the colon. It has been reported that the core 3 structure in colon cancer tissue decreases with the decrease of core 3 synthase activity.…”

Section: Discussionmentioning

confidence: 99%

Systematic Expression Analysis of the Diagnostic and Prognostic Value of HEPACAM Family Member 2 in Colon Adenocarcinoma

Wang

Ruan

Gong

et al. 2021

Preprint

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Background: The diagnostic and prognostic value of HEPACAM family member 2 (HEPACAM2) gene in patients with colon adenocarcinoma (COAD) is rarely reported. Therefore, the purpose of this study is to explore the diagnostic and prognostic value of HEPACAM2 gene in patients with COAD.Methods: Firstly, we analyzed the differential expression levels of HEPACAM2 gene and diagnostic value analysis from different databases. Secondly, univariate and multivariate survival analysis of the prognostic value of HEPACAM2 gene in patients with COAD was performed. Finally, utilizing joint-effects analysis and comprehensive prognosis analysis to investigate the prognostic value of HEPACAM2 and related genes.Results: Differential analyses of multiple databases showed that the HEPACAM2 expression level in COAD tumor tissue was significantly lower than that of adjacent normal tissues. The diagnostic ROC curve results indicated that HEPACAM2 gene had a higher diagnostic value in COAD. The RT-qPCR verification results of COAD tissue in the Guangxi cohort showed that HEPACAM2 expression level in COAD tumor tissue was significantly higher than that of adjacent normal tissues (P<0.001), and the diagnostic value was high in COAD (AUC=0.892). The prognostic value analysis showed that low expression of HEPACAM2 gene had a poorer prognosis of overall survival (OS) in patients with COAD when compared with those patients with high expression of HEPACAM2 gene ((P = 0.038, HR (95% CI) = 0.635(0.414-0.976)). Joint-effects analysis and comprehensive prognosis analysis showed that high expression of HEPACAM2 combined with high expression of CLCA1, high expression of REP15, and high expression of B3GNT6 were associated with a better prognosis of overall COAD OS.Conclusion: The results of this study suggested that the HEPACAM2 may be an independent diagnostic and prognostic biomarker for COAD.

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Section: Discussionmentioning

confidence: 99%

Systematic Expression Analysis of the Diagnostic and Prognostic Value of HEPACAM Family Member 2 in Colon Adenocarcinoma

Wang

Ruan

Gong

et al. 2021

Preprint

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“…Despite the efforts to study CRC heterogeneity, our current knowledge in this field is just the tip of the iceberg. Expanding next-generation sequencing (NGS), single-cell sequencing, and whole-exome sequencing techniques along with the application of omics data at various levels, including genomics, epigenomics, transcriptomics, peptidomics, proteinomics, and metabolomics, could give us valuable information on the heterogeneity of CRCs (116)(117)(118)(119)(120)(121)(122)(123).…”

Section: Heterogeneity Assessment Methodsmentioning

confidence: 99%

Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?

Lan

Huang

et al. 2021

Front. Oncol.

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Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.

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“…Apart from bMERB family members, Rep15 is another Rab15 effector molecule that regulates transferrin receptor trafficking. Recently multi-omics analysis data suggested REP15 as a novel colorectal cancer-specific driving gene 17 . Rep15 interacts with Rab15 at the ERC, and overexpression and depletion of Rep15 by si RNA attenuates the recycling of internalized transferrin receptor recycling via ERC without affecting receptor trafficking through sorting endosomes 18 .…”

Section: Introductionmentioning

confidence: 99%

Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector

et al. 2022

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In their GTP-bound (active) form, Rab proteins interact with effector proteins that control downstream signaling. One such Rab15 effector is Rep15, which is known to have a role in receptor recycling from the endocytic recycling compartment but otherwise remains poorly characterized. Here, we report the characterization of the Rep15:Rab15 interaction and identification of Rab3 paralogs and Rab34 as Rep15 interacting partners from a yeast two-hybrid assay. Biochemical validation of the interactions is presented and crystal structures of the Rep15:Rab3B and Rep15:Rab3C complexes provide additional mechanistic insight. We find that Rep15 adopts a globular structure that is distinct from other reported Rab15, Rab3 and Rab34 effectors. Structure-based mutagenesis experiments explain the Rep15:Rab interaction specificity. Rep15 depletion in U138MG glioblastoma cells impairs cell proliferation, cell migration and receptor recycling, underscoring the need for further clarification of the role of Rep15 in cancer.

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Multi-Omics Analysis to Identify Driving Factors in Colorectal Cancer

Cited by 14 publications

References 49 publications

Systematic Expression Analysis of the Diagnostic and Prognostic Value of HEPACAM Family Member 2 in Colon Adenocarcinoma

Systematic Expression Analysis of the Diagnostic and Prognostic Value of HEPACAM Family Member 2 in Colon Adenocarcinoma

Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?

Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector

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