A 19-Gene expression signature as a predictor of survival in colorectal cancer

Aziz, Nurul Ainin Abdul; Mokhtar, Norfilza Mohd; Harun, Roslan; Mollah, Manir Hossain; Rose, Isa Mohamed; Sagap, Ismail; Tamil, Azmi Mohd; Ngah, Wan Zurinah Wan; Jamal, A. Rahman A.

doi:10.1186/s12920-016-0218-1

Cited by 72 publications

(57 citation statements)

References 40 publications

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“…Using a newly developed monoclonal antibody against DUOX2, increased immunohistochemical staining was observed in various tumor types, including prostate, lung, breast, and colon [109]. These observations suggest that DUOX2-derived H 2 O 2 plays an important role in carcinogenesis and tumor progression, which is supported by a recent report demonstrating that DUOX2 upregulation in colorectal cancer correlates with poor prognosis[110]. Analysis of data available from the NIH funded Tissue Cancer Genome Atlas Project (TCGA) (http://cancergenome.nih.gov/) further confirms that DUOX2 is overexpressed especially in colon and esophageal cancers, although expression levels are highly variable and DUOX2 is not significantly altered in other cancers (Fig.…”

Section: Specific Roles For Duox1 and 2 In Epithelial Cancersmentioning

confidence: 82%

Paradoxical roles of dual oxidases in cancer biology

Little

Sulovari

Danyal

et al. 2017

Free Radical Biology and Medicine

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Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities.

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Section: Specific Roles For Duox1 and 2 In Epithelial Cancersmentioning

confidence: 82%

Paradoxical roles of dual oxidases in cancer biology

Little

Sulovari

Danyal

et al. 2017

Free Radical Biology and Medicine

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“…For example, increase of total plasma ceramide in the patients undergoing radiation therapy in combination with irinotecan chemotherapy was associated with favorable tumor response (Dubois et al, 2016). Analogously, CerS6 was identified as a member of the 19-gene-signature predicting survival of patients with colorectal cancer (Abdul Aziz et al, 2016). Mechanistic basis for the distinct functions of endogenous ceramides is not known; however, interaction of ceramides with specific proteins was suggested to be responsible for this, at least in part (Saddoughi et al, 2013).…”

Section: Ceramide and Cancermentioning

confidence: 99%

Ceramide Signaling and p53 Pathways

Jeffries¹,

Krupenko

2018

Advances in Cancer Research

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Ceramides, important players in signal transduction, interact with multiple cellular pathways, including p53 pathways. However, the relationship between ceramide and p53 is very complex, and mechanisms underlying their coregulation are diverse and not fully characterized. The role of p53, an important cellular regulator and a transcription factor, is linked to its tumor suppressor function. Ceramides are involved in the regulation of fundamental processes in cancer cells including cell death, proliferation, autophagy, and drug resistance. This regulation, however, can be pro-death or pro-survival depending on cancer type, the balance between ceramide species, the rate of their synthesis and utilization, and the availability of a specific array of downstream targets. This chapter highlights the central role of ceramide in sphingolipid metabolism, its role in cancer, specific effectors in ceramide pathways controlled by p53, and coregulation of ceramide and p53 signaling. We discuss the recent studies, which underscore the function of p53 in the regulation of ceramide pathways and the reciprocal regulation of p53 by ceramide. This complex relationship is based on several molecular mechanisms including the p53-dependent transcriptional regulation of enzymes in sphingolipid pathways, the activation of mutant p53 through ceramide-mediated alternative splicing, as well as modulation of the p53 function through direct and indirect effects on p53 coregulators and downstream targets. Further insight into the connections between ceramide and p53 will allow simultaneous targeting of the two pathways with a potential to yield more efficient anticancer therapeutics.

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“…The most wildly recognized prognostic biomarkers for immune therapy were programmed death ligand (PD-1), tumor mutation burden (TMB) and microsatellite instability/ mismatch repair de ciency (dMMR) 14 . However, throughout research, these solitary biomarkers only showed moderate strati cation e cacy [15][16][17][18] , more so in CRC 19 , and a universal immune-related gene (IRG) panel as prognostic signature in CRC has not been scored Within the decade, several limited-scale studies have made attempts developing predictive gene signature to stratify high-risk population with high-throughput technology [20][21][22] . However, most suffer from overtting due to insu cient sample pool, and an external validation is hardly presented.…”

Section: Introductionmentioning

confidence: 99%

Identification of an immune-related gene signature to improve prognosis prediction of colorectal cancer patients

Dai

Yao

et al. 2020

Preprint

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Background: Despite recent advance in immune therapy, great heterogeneity exists in colorectal cancer (CRC) patients’ outcome. In this study, we aimed to analyze the Immune-related gene (IRG) expression profiles from two independent public databases and develop an effective signature to forecast patients’ prognosis.Method: IRGs were collected from The Cancer Genome Atlas (TCGA) database to identify a prognostic genes signature, which was verified in Gene Expression Omnibus (GEO) database. Gene function enrichment and immune cell infiltration analyses were conducted. A prognostic nomogram was built incorporating the IRG signature with clinical risk factors.Results: The training and test datasets had 487 and 579 patients, respectively. A prognostic six-gene-signature (CCL22, LIMK1, MAPKAPK3, FLOT1, GPRC5B and IL20RB) was developed through feature selection, and yielded incredible differentiation between low and high-risk group in the training set (P < 0.001), which was confirmed in the test group (P < 0.001). The signature outperformed tumor staging regarding survival prediction. Go and KEGG functional annotation analysis suggested the signature were significantly enriched in metabolic process and regulation of immunity (P<0.05). When combined with clinical risk factors, the model showed robust prediction capability.Conclusion: The immune-related six-gene signature is a reliable prognostic indicator for CRC patients and could bring insight for personalized cancer management.

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A 19-Gene expression signature as a predictor of survival in colorectal cancer

Cited by 72 publications

References 40 publications

Paradoxical roles of dual oxidases in cancer biology

Paradoxical roles of dual oxidases in cancer biology

Ceramide Signaling and p53 Pathways

Identification of an immune-related gene signature to improve prognosis prediction of colorectal cancer patients

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