Overexpression of ANXA1 in Penile Carcinomas Positive for High-Risk HPVs

Calmon, Marília Freitas; Mota, Mânlio Tasso de Oliveira; Babeto, Erica; Cândido, Natália Maria; Girol, Ana Paula; Mendiburu, C. F.; Bonilha, Jane Lopes; Silvestre, Rodrigo Vellasco Duarte; Rosa, Bruno Miziara; Thomé, Jorge Alberto; Medeiros, Gustavo Hernandez Américo; Soares, Fernando Augusto; Guimarães, Gustavo Cardoso; Arruda, José Germano Ferraz de; Oliani, Sônia Maria; Villa, Luisa L.; Vassallo, José; Rahal, Paula

doi:10.1371/journal.pone.0053260

Cited by 18 publications

(13 citation statements)

References 50 publications

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“…It has been reported amplification and/or high expression of MYC levels in HPV-positive cases (5), high levels of ANXA1 protein in high-risk HPV cases (6), strong positive correlation between viral presence and p16…”

Section: Introductionmentioning

confidence: 99%

Genomic Profiling of Human Penile Carcinoma Predicts Worse Prognosis and Survival

Busso-Lopes

Marchi

Kuasne

et al. 2015

Cancer Prevention Research

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The molecular mechanisms underlying penile carcinoma are still poorly understood, and the detection of genetic markers would be of great benefit for these patients. In this study, we assessed the genomic profile aiming at identifying potential prognostic biomarkers in penile carcinoma. Globally, 46 penile carcinoma samples were considered to evaluate DNA copynumber alterations via array comparative genomic hybridization (aCGH) combined with human papillomavirus (HPV) genotyping. Specific genes were investigated by using qPCR, FISH, and RT-qPCR. Genomic alterations mapped at 3p and 8p were related to worse prognostic features, including advanced T and clinical stage, recurrence and death from the disease. Losses of 3p21.1-p14.3 and gains of 3q25.31-q29 were associated with reduced cancer-specific and disease-free survival. Genomic alterations detected for chromosome 3 (LAMP3, PPARG, TNFSF10 genes) and 8 (DLC1) were evaluated by qPCR. DLC1 and PPARG losses were associated with poor prognosis characteristics. Losses of DLC1 were an independent risk factor for recurrence on multivariate analysis. The gene-expression analysis showed downexpression of DLC1 and PPARG and overexpression of LAMP3 and TNFSF10 genes. Chromosome Y losses and MYC gene (8q24) gains were confirmed by FISH. HPV infection was detected in 34.8% of the samples, and 19 differential genomic regions were obtained related to viral status. At first time, we described recurrent copy-number alterations and its potential prognostic value in penile carcinomas. We also showed a specific genomic profile according to HPV infection, supporting the hypothesis that penile tumors present distinct etiologies according to virus status.

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Section: Introductionmentioning

confidence: 99%

Genomic Profiling of Human Penile Carcinoma Predicts Worse Prognosis and Survival

Busso-Lopes

Marchi

Kuasne

et al. 2015

Cancer Prevention Research

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“…ANXA1 is likely to play an oncogenic role in penile cancer associated with high-risk HPVs (Calmon et al, 2013). By contrast, the ANXA1 expression in cervical carcinogenesis has been scarcely investigated.…”

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confidence: 99%

ANXA1Ac2-26 peptide reduces ID1 expression in cervical carcinoma cultures

Prates

Franco-Salla

Santos

et al. 2015

Gene

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Cervical cancer is the second most frequent cancer in women worldwide and is associated with genetic alterations, infection with human papilloma virus (HPV), angiogenesis and inflammatory processes. The idea that inflammation is involved in tumorigenesis is supported by the frequent appearance of cancer in areas of chronic inflammation. On the other hand, the inflammatory response is controlled by the action of anti-inflammatory mediators, among these mediators, annexin A1 (ANXA1), a 37 kDa protein was detected as a modulator of inflammatory processes and is expressed by tumor cells. The study was carried out on the epithelial cancer cell line (SiHa) treated with the peptide of annexin A1 (ANXA1Ac2-26). We combined subtraction hybridization approach, Ingenuity Systems software and quantitative PCR, in order to evaluate gene expression influenced by ANXA1. We observed that ANXA1Ac2-26 inhibited proliferation in SiHa cells after 72h. In these cells, 55 genes exhibited changes in expression levels in response to peptide treatment. Six genes were selected and the expression results of 5 up-regulated genes (TPT1, LDHA, NCOA3, HIF1A, RAB13) and one down-regulated gene (ID1) were research by real time quantitative PCR. Four more genes (BMP4, BMPR1B, SMAD1 and SMAD4) of the ID1 pathway were investigated and only one (BMPR1B) shows the same down regulation. The data indicate the involvement of ANXA1Ac2-26 in the altered expression of genes involved in tumorigenic processes, which could potentially be applied as a therapeutic indicator of cervical cancer.

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“…To the best of our knowledge, the present study is the first to evaluate the expression of ANXA1 in association with HPV infection in oropharyngeal cancer, thereby demonstrating a relationship between two important and current markers for this disease. Recently, a study was published evaluating protein and mRNA expression of ANXA1 in relation to the HPV status in patients with squamous cell carcinoma of the penis [46]. This study demonstrated an increase in ANXA1 expression in HPV + carcinomas compared to the expression detected in HPV-carcinomas.…”

Section: Discussionmentioning

confidence: 91%

Relationship between HPV and biomarkers annexin A1 and P53 in oropharyngeal cancer

et al. 2014

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Background: Human papillomavirus (HPV) is often present in oropharyngeal cancers. Head and neck tumors have been examined for other molecular markers including p53 and annexin A1 (ANXA1). Here, we investigated the prevalence of HPV and its relationship with p53 and ANXA1 in patients with oropharyngeal cancer. Methods: We have analyzed tumor and adjacent mucosa from 22 patients with squamous cell carcinoma of the oropharynx in addition to samples of the oropharyngeal epithelium in subjects without cancer. We evaluated the presence of the HPV (subtypes 16/18 and 31/33) by chromogenic in situ hybridization. Additionally, we used immunofluorescence to examine the expression of p16, p53, ANXA1 and the phosphorylation of the ANXA1 residues Ser27 (ANXA1-SER) and Tyr21 (ANXA1-TYR).

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Overexpression of ANXA1 in Penile Carcinomas Positive for High-Risk HPVs

Cited by 18 publications

References 50 publications

Genomic Profiling of Human Penile Carcinoma Predicts Worse Prognosis and Survival

Genomic Profiling of Human Penile Carcinoma Predicts Worse Prognosis and Survival

ANXA1Ac2-26 peptide reduces ID1 expression in cervical carcinoma cultures

Relationship between HPV and biomarkers annexin A1 and P53 in oropharyngeal cancer

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