Proteomic analysis of human papillomavirus‐related oral squamous cell carcinoma: Identification of thioredoxin and epidermal‐fatty acid binding protein as upregulated protein markers in microdissected tumor tissue

Melle, Christian; Ernst, Günther; Winkler, Robert; Schimmel, Bettina; Klußmann, Jens Peter; Wittekindt, Claus; Guntinas‐Lichius, Orlando; Eggeling, Ferdinand von

doi:10.1002/pmic.200800882

Cited by 31 publications

(24 citation statements)

References 37 publications

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“…FABP5 (E-FAPB) is upregulated by the tumor-associated antigen EpCAM in HNSCC,(43) while proteomic analysis of HPV-related HNSCCs revealed that FABP5 was one of the proteins upregluated in these tumors. (44) One of the proteins with lower spectral counts in HNSCC was GBP6. The presumed function of this protein is to bind guanylate and to hydrolyze GTP to both GDP and GMP but no data is available for this specific for of GBP.…”

Section: Resultsmentioning

confidence: 99%

Comparative Shotgun Proteomics Using Spectral Count Data and Quasi-Likelihood Modeling

Gray

Zhang

et al. 2010

J. Proteome Res.

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Shotgun proteomics provides the most powerful analytical platform for global inventory of complex proteomes using liquid chromatography−tandem mass spectrometry (LC−MS/MS) and allows a global analysis of protein changes. Nevertheless, sampling of complex proteomes by current shotgun proteomics platforms is incomplete, and this contributes to variability in assessment of peptide and protein inventories by spectral counting approaches. Thus, shotgun proteomics data pose challenges in comparing proteomes from different biological states. We developed an analysis strategy using quasi-likelihood Generalized Linear Modeling (GLM), included in a graphical interface software package (QuasiTel) that reads standard output from protein assemblies created by IDPicker, an HTML-based user interface to query shotgun proteomic data sets. This approach was compared to four other statistical analysis strategies: Student t test, Wilcoxon rank test, Fisher’s Exact test, and Poisson-based GLM. We analyzed the performance of these tests to identify differences in protein levels based on spectral counts in a shotgun data set in which equimolar amounts of 48 human proteins were spiked at different levels into whole yeast lysates. Both GLM approaches and the Fisher Exact test performed adequately, each with their unique limitations. We subsequently compared the proteomes of normal tonsil epithelium and HNSCC using this approach and identified 86 proteins with differential spectral counts between normal tonsil epithelium and HNSCC. We selected 18 proteins from this comparison for verification of protein levels between the individual normal and tumor tissues using liquid chromatography−multiple reaction monitoring mass spectrometry (LC−MRM-MS). This analysis confirmed the magnitude and direction of the protein expression differences in all 6 proteins for which reliable data could be obtained. Our analysis demonstrates that shotgun proteomic data sets from different tissue phenotypes are sufficiently rich in quantitative information and that statistically significant differences in proteins spectral counts reflect the underlying biology of the samples.

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Section: Resultsmentioning

confidence: 99%

Comparative Shotgun Proteomics Using Spectral Count Data and Quasi-Likelihood Modeling

Gray

Zhang

et al. 2010

J. Proteome Res.

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“…Fatty acid binding protein 5 (psoriasis-associated, FABP5), found in epidermal cells, was first identified to be up-regulated in psoriasis keratinocytes [34]. In cancer cells, FABP5 increases cell proliferation and invasiveness, as recently demonstrated in oral squamous cell carcinoma [35] where its expression may be HPV-related [36]. In non-cancer keratinocytes FABP5 elevation may be necessary for the activation of cell motility during epidermal wound healing [37].…”

Section: Discussionmentioning

confidence: 99%

Estimation of groin recurrence risk in patients with squamous cell vulvar carcinoma by the assessment of marker gene expression in the lymph nodes

et al. 2012

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BackgroundRegional lymph node (LN) status is a well-known prognostic factor for vulvar carcinoma (VC) patients. Although the reliable LN assessment in VC is crucial, it presents significant diagnostic problems. We aimed to identify specific mRNA markers of VC dissemination in the LN and to address the feasibility of predicting the risk of nodal recurrence by the patterns of gene expression.MethodsSentinel and inguinal LN samples from 20 patients who had undergone surgery for stage T1-3, N0-2, M0 primary vulvar squamous cell carcinoma were analyzed. Gene expression profiles were assessed in four metastatic [LN(+)] and four histologically negative [LN(−)] lymph node samples obtained from four VC patients, by the Affymetrix U133 Plus 2.0 gene expression microarrays. Of the set of genes of the highest expression in the metastatic LNs compared to LN(−), seven candidate marker genes were selected: PERP, S100A8, FABP5, SFN, CA12, JUP and CSTA, and the expression levels of these genes were further analyzed by the real-time reverse transcription polymerase chain reaction (qRT-PCR) in 71 LN samples.ResultsAll of the seven genes in question were significantly increased in LN(+) compared to LN(−) samples. In the initial validation of the seven putative markers of metastatic LN, the Cox proportional hazard model pointed to SFN, CA12 and JUP expression to significantly relate to the time to groin recurrence in VC patients.ConclusionsOur findings first provided evidence that SFN, CA12 and JUP have a potential of marker genes for the prediction of the groin recurrence LN in VC patients.

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“…Thioredoxin (TRX) and epidermal fatty acid binding protein (E-FABP) were identified by proteomics to be upregulated in HPV-related tumors [22]. TRX is a redox mediator promoting cell survival, e.g., under hypoxic conditions and oxidative stress.…”

Section: Protein Expression Alterationsmentioning

confidence: 99%

Human Papillomavirus-Related Head and Neck Cancer

Wagner¹,

Sharma²,

Wuerdemann³

et al. 2017

Oncol Res Treat

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Human papillomavirus(HPV)-related head and neck cancer is recognized as a distinct tumor entity with rising incidence reported for several countries. These tumors arise from squamous cells, typically in the oropharynx. In contrast to cancer associated with other risk factors, HPV-related cancer is driven by viral oncoprotein activity and has individual profiles regarding protein expression, and genetic and epigenetic alterations. Molecular characteristics are p16^IN4A overexpression, absence of p53 inactivating mutations, and PI3K/AKT and Wnt pathway modulation. Patients with HPV-related head and neck cancer have improved survival compared to those with HPV-negative tumors, and p16^INK4A staining has been introduced into tumor staging recently. However, no specific or toxicity-reduced treatment modalities have been established for this entity so far. Although the still incomplete and partially inconsistent data in this field needs further study, particular features of HPV-related cancers such as specific microRNA expression, immunology, or gene methylation patterns certainly have the potential to be implemented in future diagnostic and therapeutic concepts.

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Proteomic analysis of human papillomavirus‐related oral squamous cell carcinoma: Identification of thioredoxin and epidermal‐fatty acid binding protein as upregulated protein markers in microdissected tumor tissue

Cited by 31 publications

References 37 publications

Comparative Shotgun Proteomics Using Spectral Count Data and Quasi-Likelihood Modeling

Comparative Shotgun Proteomics Using Spectral Count Data and Quasi-Likelihood Modeling

Estimation of groin recurrence risk in patients with squamous cell vulvar carcinoma by the assessment of marker gene expression in the lymph nodes

Human Papillomavirus-Related Head and Neck Cancer

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