Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis

Yang, Ke; Zhang, Shizhou; Zhang, Dongsheng; Tao, Qian; Zhang, Tianqi; Liu, Guijun; Liu, Xingguang; Zhao, Tengda

doi:10.1007/s10147-019-01435-9

“…Consistent with our results, pathological stagerelated hub gene role of COL1A1, COL1A2, COL5A1 were reported earlier by another group [43]. The hub gene role of ACTA1 was found in prostate cancer [44] and the prognostic role of ACTA1 was found in head and neck squamous cell carcinoma (HNSCC) [45]. The important role of DCN in cancer was mentioned by several studies.…”

Section: Discussionsupporting

confidence: 92%

Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes

Chen

¹

,

Liu

²

,

Liu

³

et al. 2020

Preprint

0

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Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8 + T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8 + T cells, and molecular subtypes. Mutated genes, KEGG pathways, GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8 + T cells, and TMB is about 36% predictable. PIK3CA, RB1, FGFR3, KMT2C, MACF1, RYR2, and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. This study identified which MIBC patients are suitable for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.

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“…Consistent with our results, pathological stagerelated hub gene role of COL1A1, COL1A2, COL5A1 were reported earlier by another group [43]. The hub gene role of ACTA1 was found in prostate cancer [44] and the prognostic role of ACTA1 was found in head and neck squamous cell carcinoma (HNSCC) [45]. The experimental study suggests that Decorin does not affect directly anti-tumoural immune response, yet is required for e cient invasiveness in vitro [46].…”

Section: Discussionsupporting

confidence: 91%

Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes

Chen

¹

,

Liu

²

,

Liu

³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA , RB1 , FGFR3 , KMT2C , MACF1 , RYR2 , and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.Immunotherapy, especially anti-PD-1, is becoming a pillar of modern muscle-invasive bladder cancer (MIBC) treatment. However, the objective response rates (ORR) are relatively low due to the lack of precise biomarkers to select patients. Herein, the molecular subtype, tumor mutation burden (TMB), and CD8+ T cells were calculated by the gene expression and mutation profiles of MIBC patients. MIBC immunotypes were constructed using clustering analysis based on tumor mutation burden, CD8+ T cells, and molecular subtypes. Mutated genes, enriched functional KEGG pathways and GO terms, and co-expressed network-specific hub genes have been identified. We demonstrated that ORR of immunotype A patients identified by molecular subtype, CD8+ T cells, and TMB is about 36% predictable. PIK3CA , RB1 , FGFR3 , KMT2C , MACF1 , RYR2 , and EP300 are differentially mutated among three immunotypes. Pathways such as ECM-receptor interaction, PI3K-Akt signaling pathway, and TGF-beta signaling pathway are top-ranked in enrichment analysis. Low expression of ACTA2 was associated with the MIBC survival benefit. The current study constructs a model that could identify suitable MIBC patients for immunotherapy, and it is an important step forward to the personalized treatment of bladder cancers.

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“…PDGFA, a member of the platelet-derived growth factor (PDGF) family, may play a crucial role in the composition of the immune microenvironment 20 . PLAU, one of the major proteolytic enzymes involved in the degradation of extracellular matrix, has been demonstrated to play a critical role in tissue remodeling and migration in the developmental of cancer and in tumorigenesis 21 . Some studies indicated that PLAU was a marker to predict OS in HNSCC patients 22 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive immunogenomic landscape analysis of prognosis-related genes in head and neck cancer

Li

¹

,

Wang

²

,

Lei

³

et al. 2020

Sci Rep

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Head and neck cancer is the sixth most common malignancy around the world, and 90% of cases are squamous cell carcinomas. In this study, we performed a systematic investigation of the immunogenomic landscape to identify prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC). We analyzed the expression profiles of immune-related genes (IRGs) and clinical characteristics by interrogating RNA-seq data from 527 HNSCC patients in the cancer genome atlas (TCGA) dataset, including 41 HPV+ and 486 HPV− samples. We found that differentially expressed immune genes were closely associated with patient prognosis in HNSCC by comparing the differences in gene expression between cancer and normal samples and performing survival analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological functions of the differentially expressed immunogenomic prognosisrelated genes. Two additional cohorts from the Oncomine database were used for validation. 65, 56 differentially expressed IRGs was associated with clinical prognosis in total and HPVsamples, respectively. Furthermore, we extracted 10, 11 prognosis-related IRGs from 65, 56 differentially expressed IRGs, respectively. They were significantly correlated with clinical prognosis and used to construct the prognosis prediction models. The multivariable ROC curves (specifically, the AUC) were used to measure the accuracy of the prognostic models. these genes were mainly enriched in several gene ontology (GO) terms related to immunocyte migration and receptor and ligand activity. KEGG pathway analysis revealed enrichment of pathways related to cytokine−cytokine receptor interactions, which are primarily involved in biological processes. In addition, we identified 63 differentially expressed transcription factors (TFs) from 4784 differentially expressed genes, and 16 edges involving 18 nodes were formed in the regulatory network between differentially expressed TFs and the high-risk survival-associated IRGs. B cell and CD4 T cell infiltration levels were significantly negatively correlated with the expression of prognosis-related immune genes regardless of HPV status. In conclusion, this comprehensive analysis identified the prognostic IRGs as potential biomarkers, and the model generated in this study may enable an accurate prediction of survival. Head and neck cancer is a common malignancy accounting for 5-10% of cancers worldwide. Head and neck squamous cell carcinoma constitutes 90% of head and neck cancers, which arises from the pharynx, the oral cavity and lip, the ear, the larynx, the nasal cavity, the salivary glands and the paranasal sinuses 1-3. The tobacco, alcohol use and human papillomavirus (HPV) infection are important causes of head and neck squamous cell carcinoma 4. HNSCC represents a biologically complex disease process and a heterogeneous collection of tumors in which multiple pathways are altered, leading to the development of HNSCC, and the mechanisms leading to this disease...

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Identification of SERPINE1, PLAU and ACTA1 as biomarkers of head and neck squamous cell carcinoma based on integrated bioinformatics analysis

Cited by 66 publications

References 33 publications

Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes

Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes

Defining muscle-invasive bladder cancer immunotypes by introducing tumor mutation burden, CD8+ T cells, and molecular subtypes

Comprehensive immunogenomic landscape analysis of prognosis-related genes in head and neck cancer

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