Deciphering The Potential Role of Hox Genes in Pancreatic Cancer

Kuo, Tzu-Lei; Cheng, Kuang‐Hung; Chen, Li-Tzong; Hung, Wen‐Chun

doi:10.3390/cancers11050734

Cited by 24 publications

(17 citation statements)

References 62 publications

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“…In addition, we found that the expression levels of HOXA6 and HOXA10 were significantly high in AML. This result is similar to findings in lung adenocarcinomas [51], breast cancer [52] and prostate cancer [53]. However, no such evidence has been reported in AML.…”

Section: Kaplan-meier Survival Analysissupporting

confidence: 88%

Weighted gene coexpression network analysis identifies critical genes in different subtypes of acute myeloid leukaemia

Xin

et al. 2020

Biotechnology & Biotechnological Equipment

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Acute myeloid leukaemia (AML) is a common blood cancer with rapid progression and a high death rate. The aim of this study was to illustrate the molecular mechanism and identify potential prognostic genes by performing weighted gene coexpression network analysis (WGCNA) of AML. WGCNA of AML was performed with R software based on GDC The Cancer Genome Atlas (TCGA) Acute Myeloid Leukaemia (LAML) RNA-seq data from TCGA database. The gene modules showing significant correlation with the M0-M7 subtypes and the NPMc mutation were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Hub genes from the key modules were identified using the cytoHubba package, and the prognostic values of these hub genes were analysed with a Cox proportional hazards model based on TCGA clinical data. A total of 151 patients from the TCGA database with RNA-seq data were included in the present study. The weighted gene coexpression network contained 21 coexpression modules. Three modules (blue, yellow and purple) were highly correlated with AML subtypes and the NPMc mutation. In total, six key hub genes were identified from the AML subtype-and NPMc mutation-related modules: TLR8, SLC15A3, ADAP2, HOXA6 and HOXA10. Kaplan-Meier curve analysis showed that the five hub genes in the gene expression network are significantly associated with AML prognosis. WGCNA of AML performed in the present study revealed potential prognostic genes that not only have important clinical significance for prognosis but also provide important clues for identifying effective targets in AML therapeutic strategies.

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Section: Kaplan-meier Survival Analysissupporting

confidence: 88%

Weighted gene coexpression network analysis identifies critical genes in different subtypes of acute myeloid leukaemia

Xin

et al. 2020

Biotechnology & Biotechnological Equipment

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“…HOX proteins function as oncogenes or tumour suppressors, depending on the context [4]. An increasing number of HOX proteins have been investigated in various tumours, including acute myeloid leukaemia [5], breast cancer [6], lung cancer [7], and digestive tract neoplasms [8][9][10]. Currently, the implications of HOX proteins in tumorigenesis and development of GC have been reported in many studies.…”

Section: Introductionmentioning

confidence: 99%

Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

Jin

Dai

et al. 2020

BMC Cancer

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Background An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and action mechanisms of HOX proteins in GC. Methods A comprehensive search of PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX protein expression on the prognosis and clinicopathological features of GC, respectively. Results Nineteen studies containing 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I2 = 90.5%, p = 0.000). According to the subgroup analysis, increased expression of HOX protein in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36–0.59, I2 = 3.1%, p = 0.377), while overexpression of HOX protein in the upregulated subgroup was correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79–3.74, I2 = 73.5%, p = 0.000). The aberrant expression of HOX protein was crucially related to the TNM stage, depth of tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC. In addition, the molecular mechanisms by which HOX proteins regulate tumorigenesis and development of GC were also explored. Conclusions HOX proteins play vital roles in GC progression, which might serve as prognostic markers and therapeutic targets for GC.

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“…15 Deregulation of HOX genes has also been identified in cancer. 16–18 Several studies reported differences between normal and tumor conditions as reviewed by Bathlekar et al 12 and also the role of HOX genes in cancer susceptibility and progression; 19 however, assigning a specific role for HOX genes as drivers of the malignant phenotype requires further investigation. Evidence that HOX genes may be deregulated in different ways in different types of cancer is accumulating.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Homeobox genes function as master regulatory transcription factors during development, and their expression is often altered in cancer. The HOX gene family was initially studied intensively to understand how the expression of each gene was involved in forming axial patterns and shaping the body plan during embryogenesis. More recent investigations have discovered that HOX genes can also play an important role in cancer. 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. New studies are also emerging, showing the critical role of some members of the HOX gene family in tumor progression and variation in clinical response. However, there has been limited systematic evaluation of the various contributions of each member of the HOX gene family in the pathways that drive the common phenotypic changes (or “hallmarks”) and that underlie the transformation of normal cells to cancer cells. In this review, we investigate the context of the engagement of HOX gene targets and their downstream pathways in the acquisition of competence of tumor cells to undergo malignant transformation and tumor progression. We also summarize published findings on the involvement of HOX genes in carcinogenesis and use bioinformatics methods to examine how their downstream targets and pathways are involved in each hallmark of the cancer phenotype.

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Deciphering The Potential Role of Hox Genes in Pancreatic Cancer

Cited by 24 publications

References 62 publications

Weighted gene coexpression network analysis identifies critical genes in different subtypes of acute myeloid leukaemia

Weighted gene coexpression network analysis identifies critical genes in different subtypes of acute myeloid leukaemia

Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

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

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