P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients

Kappler, Matthias; Kotrba, Johanna; Kaune, Tom; Bache, Matthias; Rot, Swetlana; Bethmann, Daniel; Wichmann, Henri; Güttler, Antje; Bilkenroth, Udo; Horter, Susanne; Gallwitz, Lisa; Kessler, Jacqueline; Greither, Thomas; Täubert, Helge; Eckert, Alexander W.; Vordermark, Dirk

doi:10.1016/j.ctro.2017.05.002

Cited by 23 publications

(22 citation statements)

References 35 publications

(47 reference statements)

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“…Interestingly, one research suggested that those three hypoxia signatures might be replaced by P4HA1 [28] and another study also confirmed that P4HA1 was a significantly prognostic factor for oral squamous cell carcinoma patients [29]. We also got a similar result in NPC patients.…”

Section: Discussionsupporting

confidence: 72%

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis

et al. 2020

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Background Despite improvements in nasopharyngeal carcinoma (NPC) treatment, patients with recurrence and metastasis still have a poor prognosis. Thus, the identification of novel biomarkers is urgently needed to predict outcomes and tailor treatment for NPC. Methods Four data sets were downloaded from Gene Expression Omnibus, and one data set GSE68799 of which was applied to filtrate key modules and hub genes by construction of a co-expression network. Other data sets (GSE12452 and GSE53819) were used to verify hub genes. The data set GSE102349 was devoted to identify prognostic hub genes by survival analysis. To explored whether prognostic hub genes are related to hypoxia signatures in NPC, correlation analysis was carried out, and followed by functional verification experiments of those genes in vitro. Results By co-expression network analysis, blue module was regarded as a key module in the benign and malignant group, and IGSF9 of the blue module was identified as a prognostic hub gene. Moreover, IGSF9 is expected to be a innovative hypoxia-related gene in NPC based on the strong associativity between expression of IGSF9 and hypoxia scores of three signatures (99-gene, 26-gene and 15-gene). Further functional studies verified that down-regulated expression of IGSF9 could reduce the proliferation, migration and invasion ability of NPC cells, and hypoxia could induce the expression of IGSF9. Conclusion IGSF9 was identified to be relevant to prognosis and involved in hypoxia in NPC. IGSF9 might serve as one novel prognostic indicator of NPC in the future.

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Section: Discussionsupporting

confidence: 72%

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis

et al. 2020

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“…Of note, the authors found a P4HA1-HIF1α positive feedback loop, which regulates the glycolytic and oncogenic activities of PDAC, their stemness and chemoresistance (50). Additionally, high P4HA1 expression is a poor prognostic factor for head and neck squamous cell carcinoma (51), oral squamous cell carcinoma (52), and prostate cancer (53). In ovarian cancer P4HA1 promotes migration, invasion, EMT and metastasis formation (54).…”

Section: Collagen-prolyl Hydroxylation In Cancer Progressionmentioning

confidence: 99%

Proline Metabolism in Tumor Growth and Metastatic Progression

et al. 2020

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Cancer cells show a formidable capacity to survive under stringent conditions, to elude mechanisms of control, such as apoptosis, and to resist therapy. Cancer cells reprogram their metabolism to support uncontrolled proliferation and metastatic progression. Phenotypic and functional heterogeneity are hallmarks of cancer cells, which endow them with aggressiveness, metastatic capacity, and resistance to therapy. This heterogeneity is regulated by a variety of intrinsic and extrinsic stimuli including those from the tumor microenvironment. Increasing evidence points to a key role for the metabolism of non-essential amino acids in this complex scenario. Here we discuss the impact of proline metabolism in cancer development and progression, with particular emphasis on the enzymes involved in proline synthesis and catabolism, which are linked to pathways of energy, redox, and anaplerosis. In particular, we emphasize how proline availability influences collagen synthesis and maturation and the acquisition of cancer cell plasticity and heterogeneity. Specifically, we propose a model whereby proline availability generates a cycle based on collagen synthesis and degradation, which, in turn, influences the epigenetic landscape and tumor heterogeneity. Therapeutic strategies targeting this metabolic-epigenetic axis hold great promise for the treatment of metastatic cancers.

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“…Previously, the increased P4HA1 expression correlates with poor prognosis has been demonstrated in several cancers, including breast cancer, oral squamous cell carcinoma, melanoma, and prostate cancer [55][56][57][58] . However, we know little about how P4HA1 promotes tumor progression in the past.…”

Section: Discussionmentioning

confidence: 96%

Persistent cell proliferation signals correlates with increased glycolysis in tumor hypoxia microenvironment across cancer types

Wei

Huang

et al. 2020

Preprint

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Background：Altered metabolism is a hallmark of cancer and glycolysis is one of the important factors promoting tumor development. Given that the absence of multi-sample big data research about glycolysis, the molecular mechanisms involved in glycolysis or the relationships between glycolysis and tumor microenvironment are not fully studied. Thus, a more comprehensive approach in a pan-cancer landscape may be needed.Methods: Here, we develop a computational pipeline to study multi-omics molecular features defining glycolysis activity and identify molecular alterations that correlate with glycolysis.We apply a 22-gene expression signature to define the glycolysis activity landscape and verify the robustness using clinically defined glycolysis samples from several previous studies. Based on gene expression signature, we classify about 5552 of 9229 tumor samples into glycolysis score-high and score-low groups across 25 cancer types from The Cancer Genome Atlas (TCGA) and demonstrate their prognostic associations. Moreover, using genomes and transcriptome data, we characterize the association of copy-number aberrations (CNAs), somatic single-nucleotide variants (SNVs) and hypoxia signature with glycolysis activity.Findings: Gene set variation analysis (GSVA) score by gene set expression was verified robustly to represent glycolytic activity and highly glycolytic tumors presented a poor overall survival in some cancer types. Then, we identified various types of molecular features promoting tumor cell proliferation were associated with glycolysis activity. Our study showed that TCA cycle and respiration electron transport were active in glycolysis-high tumors, indicating glycolysis was not a symptom of impaired oxidative metabolism. The glycolytic score significantly correlated with hypoxia score across all 3 cancer types. Glycolysis score was also associated with elevated genomic instability. In all tumor types, high glycolysis tumors exhibited characteristic driver genes altered by CNAs identified multiple oncogenes and tumor suppressors. We observed widespread glycolysis-associated dysregulation of mRNA across cancers and screened out HSPA8 and P4HA1 as the potential modulating factor to glycolysis. Besides, the expression of genes encoding glycolytic enzymes positively correlated with genes in cell cycle.Interpretation: This is the first study to identify gene expression signatures that reflect glycolysis activity, which can be easily applied to large numbers of patient samples. Our analysis establishes a computational framework for characterizing glycolysis activity using gene expression data and defines correlation of glycolysis with the hypoxia microenvironment, tumor cell cycle and proliferation at a pan-cancer landscape. The findings suggest that the mechanisms whereby hypoxia influence glycolysis are likely multifactorial.Our finding is significant not just in demonstrating definition value for glycolysis but also in providing a comprehensive molecular-level understanding of glycolysis and suggesting a framewo...

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P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell carcinoma patients

Cited by 23 publications

References 35 publications

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis

Proline Metabolism in Tumor Growth and Metastatic Progression

Persistent cell proliferation signals correlates with increased glycolysis in tumor hypoxia microenvironment across cancer types

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