Contributions of HOX genes to cancer hallmarks: Enrichment pathway analysis and review

Brotto, Danielle Barbosa; Siena, Ádamo Davi Diógenes; Barros, Isabela Ichihara de; Carvalho, Simone da Costa e Silva; Muys, Bruna Rodrigues; Goedert, Lucas; Cardoso, Cibele C.; Plaça, Jéssica Rodrigues; Ramão, Anelisa; Squire, Jeremy A.; Araújo, Luíza Ferreira de; Silva, Wilson A.

doi:10.1177/1010428320918050

Cited by 49 publications

(43 citation statements)

References 165 publications

(215 reference statements)

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“…The family consists mainly of HOX genes, which are master regulatory transcription factors in embryogenesis, cellular development, and issue homeostasis (Li B. et al, 2019 ). Recent researches have shown that depending on the type of the tumor, the expression of HOX genes may be increased or decreased and play roles in oncogenesis or tumor suppression (Shah and Sukumar, 2010 ; Bhatlekar et al, 2014 ; Brotto et al, 2020 ). (5) Keratin-associated proteins have no confirmed role in cancer.…”

Section: Resultsmentioning

confidence: 99%

Signatures of Discriminative Copy Number Aberrations in 31 Cancer Subtypes

Gao

Baudis

2021

Front. Genet.

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Copy number aberrations (CNA) are one of the most important classes of genomic mutations related to oncogenetic effects. In the past three decades, a vast amount of CNA data has been generated by molecular-cytogenetic and genome sequencing based methods. While this data has been instrumental in the identification of cancer-related genes and promoted research into the relation between CNA and histo-pathologically defined cancer types, the heterogeneity of source data and derived CNV profiles pose great challenges for data integration and comparative analysis. Furthermore, a majority of existing studies have been focused on the association of CNA to pre-selected “driver” genes with limited application to rare drivers and other genomic elements. In this study, we developed a bioinformatics pipeline to integrate a collection of 44,988 high-quality CNA profiles of high diversity. Using a hybrid model of neural networks and attention algorithm, we generated the CNA signatures of 31 cancer subtypes, depicting the uniqueness of their respective CNA landscapes. Finally, we constructed a multi-label classifier to identify the cancer type and the organ of origin from copy number profiling data. The investigation of the signatures suggested common patterns, not only of physiologically related cancer types but also of clinico-pathologically distant cancer types such as different cancers originating from the neural crest. Further experiments of classification models confirmed the effectiveness of the signatures in distinguishing different cancer types and demonstrated their potential in tumor classification.

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Section: Resultsmentioning

confidence: 99%

Signatures of Discriminative Copy Number Aberrations in 31 Cancer Subtypes

Gao

Baudis

2021

Front. Genet.

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“…More recent investigations have discovered that HOXA9 can act as both an oncogene and a tumour suppressor gene in a context-dependent manner. 25 The literature has shown that the expression of HOX genes may be increased or decreased in different tumors and that these alterations may differ depending on the specific HOX gene involved and the type of cancer being investigated. 25 , 26 However, conditions under which it assumes either role remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

HOXA9 Expression is Associated with Advanced Tumour Stage and Prognosis in Nasopharyngeal Carcinoma

Liu¹,

Ji²,

Sun³

et al. 2021

CMAR

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Background: Homeobox A9 (HOXA9), a member of the HOX protein family, plays diverse biological roles in embryonic development and carcinogenesis. The prognostic value of HOXA9 expression in nasopharyngeal carcinoma (NPC) is not well-defined. The present study aimed to analyse NPC tissue HOXA9 expression and determine prognostic significance by investigating the relationship between HOXA9 expression and clinicopathologic features. Methods: Between January 2010 and December 2014, 252 NPC patients and 30 chronic nasopharyngitis patients (control group) were recruited to participate in the present study.Correlations between HOXA9 expression level and clinicopathologic features (including survival) were analysed. Results: High HOXA9 expression was significantly associated with clinical stage (p < 0.01) and higher T stage (p < 0.01). In univariate analysis, high HOXA9 expression predicted overall survival (OS) (p = 0.011). In multivariate analysis, HOXA9 over-expression independently and significantly predicted poorer PFS (p < 0.01, hazard ratio (HR) = 2.387, 95% CI [0.876, 6.545]) and OS (p < 0.01, HR = 2.486, 95% CI [1.041, 8.926]). Conclusion: High HOXA9 expression is an independent prognostic factor associated with advanced tumour stage and poorer survival in NPC patients.

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“…In mammals, the HOX network consists of 39 genes that exhibit a high degree of sequence similarity, particularly in the homeobox domain. Homeobox genes function as master regulatory transcription factors during development, and their expression is often altered in cancer (Brotto et al, 2020;Li et al, 2020;Qu et al, 2019). Many of the chromosomal translocations associated with acute leukemias involve HOX genes, such as mixed lineage leukemia, which leads to the inappropriate expression of specific HOX gene subsets (Collins & Thompson, 2018;Dickson, Lappin & Thompson, 2009).…”

Section: Overview Of Mrgsmentioning

confidence: 99%

Master regulator genes and their impact on major diseases

Cai

Zhou

Han

et al. 2020

PeerJ

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Master regulator genes (MRGs) have become a hot topic in recent decades. They not only affect the development of tissue and organ systems but also play a role in other signal pathways by regulating additional MRGs. Because a MRG can regulate the concurrent expression of several genes, its mutation often leads to major diseases. Moreover, the occurrence of many tumors and cardiovascular and nervous system diseases are closely related to MRG changes. With the development in omics technology, an increasing amount of investigations will be directed toward MRGs because their regulation involves all aspects of an organism’s development. This review focuses on the definition and classification of MRGs as well as their influence on disease regulation.

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Contributions of HOX genes to cancer hallmarks: Enrichment pathway analysis and review

Cited by 49 publications

References 165 publications

Signatures of Discriminative Copy Number Aberrations in 31 Cancer Subtypes

Signatures of Discriminative Copy Number Aberrations in 31 Cancer Subtypes

HOXA9 Expression is Associated with Advanced Tumour Stage and Prognosis in Nasopharyngeal Carcinoma

Master regulator genes and their impact on major diseases

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