Research

11 pages, 1638 KiB

Open AccessArticle

Clinical Significance of CUB and Sushi Multiple Domains 1 Inactivation in Head and Neck Squamous Cell Carcinoma

by Ah Ra Jung, Young-Gyu Eun, Young Chan Lee, Joo Kyung Noh and Kee Hwan Kwon

Int. J. Mol. Sci. 2018, 19(12), 3996; https://doi.org/10.3390/ijms19123996 - 12 Dec 2018

Cited by 11 | Viewed by 3197

Although the genetic alteration of CUB and Sushi multiple domains 1 (CSMD1) is known to be associated with poor prognosis in several cancers, there is a lack of clinical relevance in head and neck cancer. The aim of this study was to offer [...] Read more.

Although the genetic alteration of CUB and Sushi multiple domains 1 (CSMD1) is known to be associated with poor prognosis in several cancers, there is a lack of clinical relevance in head and neck cancer. The aim of this study was to offer insight into the clinical significance of CSMD1, utilizing a multimodal approach that leverages publicly available independent genome-wide expression datasets. CSMD1-related genes were found and analyzed to examine the clinical significance of CSMD1 inactivation in the HNSCC cohort of publicly available databases. We analyzed the frequency of somatic mutations, clinicopathologic characteristics, association with immunotherapy-related gene signatures, and the pathways of gene signatures. We found 363 CSMD1-related genes. The prognosis of the CSMD1-inactivated subgroup was poor. FBXW7, HLA-A, MED1, NOTCH2, NOTCH3, and TP53 had higher mutation rates in the CSMD1-inactivated subgroups. The Interferon-gamma score and immune signature score were elevated in CSMD1-inactivated subgroups. We identified several CSMD1-related pathways, such as the phosphatidylinositol signaling system and inositol phosphate metabolism. Our study using three large and independent datasets suggests that CSMD1-related gene signatures are associated with the prognosis of HNSCC patients. Full article

(This article belongs to the Special Issue Head and Neck Cancers: Diagnostic, Prognostic and Predictive Biomarkers)

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13 pages, 1191 KiB

Open AccessArticle

Increased Plasma Circulating Cell-Free DNA Could Be a Potential Marker for Oral Cancer

by Li-Han Lin, Kuo-Wei Chang, Shou-Yen Kao, Hui-Wen Cheng and Chung-Ji Liu

Int. J. Mol. Sci. 2018, 19(11), 3303; https://doi.org/10.3390/ijms19113303 - 24 Oct 2018

Cited by 52 | Viewed by 5379

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a disease that affects patients worldwide. DNA of dead cells is released into the blood stream and may be isolated from plasma or serum samples. This DNA is termed cell-free DNA (cfDNA). cfDNA is increased in [...] Read more.

Background: Oral squamous cell carcinoma (OSCC) is a disease that affects patients worldwide. DNA of dead cells is released into the blood stream and may be isolated from plasma or serum samples. This DNA is termed cell-free DNA (cfDNA). cfDNA is increased in several types of malignancies. We investigated if there was a correlation between cfDNA levels and the progression of OSCC. Methods: Using quantitative spectrometry, we measured plasma cfDNA in 121 patients with OSCC and 50 matched controls. Mann Whitney and Wilcoxon tests were used to compare differences among various clinical variants. Receiver operating characteristic (ROC) analysis was used to obtain levels suitable for the separation of the clinical subsets. Kaplan-Meier analysis was used to assess correlation with survival. Results: Plasma cfDNA was significantly elevated in patients with OSCC relative to controls. Plasma cfDNA levels correlated with larger tumor size, cervical lymph node metastasis and late stage. Higher plasma cfDNA levels were associated with a poor prognosis of OSCC, which is a new finding. Conclusion: Plasma cfDNA could serve as a novel and easily accessible biomarker in OSCC, providing diagnostic and prognostic value. Full article

(This article belongs to the Special Issue Head and Neck Cancers: Diagnostic, Prognostic and Predictive Biomarkers)

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13 pages, 2654 KiB

Open AccessArticle

Integrative Histologic and Bioinformatics Analysis of BIRC5/Survivin Expression in Oral Squamous Cell Carcinoma

by Giuseppe Troiano, Agostino Guida, Gabriella Aquino, Gerardo Botti, Nunzia Simona Losito, Silvana Papagerakis, Maria Carmela Pedicillo, Franco Ionna, Francesco Longo, Monica Cantile, Antonio Pennella, Lucio Lo Russo, Giovanni Di Gioia, Maria Addolorata Mariggiò, Lorenzo Lo Muzio and Giuseppe Pannone

Int. J. Mol. Sci. 2018, 19(9), 2664; https://doi.org/10.3390/ijms19092664 - 08 Sep 2018

Cited by 21 | Viewed by 4630

Abstract

Survivin is a well-known protein involved in the inhibition of apoptosis in many different cancer types. The aim of this study was to perform an integrated bioinformatic and histologic analysis in order to study the expression and prognostic role of Survivin and its [...] Read more.

Survivin is a well-known protein involved in the inhibition of apoptosis in many different cancer types. The aim of this study was to perform an integrated bioinformatic and histologic analysis in order to study the expression and prognostic role of Survivin and its related gene BIRC5 in oral cancer. Publicly available databases were accessed via Gene Expression Omnibus and Oncomine, in addition raw data from The Cancer Genome Atlas (TCGA) were also obtained in order to analyze the rate of gene mutation, expression and methylation in patients with oral squamous cells carcinoma (OSCC). Immunohistochemistry (IHC) was also performed in order to evaluate the nuclear and cytoplasmic expression of Survivin and their correlation with cell proliferation in samples from OSCC patients. Results of this study revealed that Survivin is rarely mutated in OSCC samples and upregulated when compared to non-cancerous tissue. A negative correlation between the methylation of the island cg25986496 and BIRC5 mRNA expression was detected from TCGA data. IHC staining revealed that cytoplasmic (and not nuclear) expression of Survivin is associated with poor overall survival in OSCC patients, while the nuclear expression correlates with higher proliferation rate. In addition, data from TCGA database revealed that BIRC5 gene expression is an independent prognostic factor for OSCC patients. Full article

(This article belongs to the Special Issue Head and Neck Cancers: Diagnostic, Prognostic and Predictive Biomarkers)

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13 pages, 1297 KiB

Open AccessArticle

A Noninvasive Test for MicroRNA Expression in Oral Squamous Cell Carcinoma

by Davide B. Gissi, Luca Morandi, Andrea Gabusi, Achille Tarsitano, Claudio Marchetti, Francesca Cura, Annalisa Palmieri, Lucio Montebugnoli, Sofia Asioli, Maria P. Foschini and Luca Scapoli

Int. J. Mol. Sci. 2018, 19(6), 1789; https://doi.org/10.3390/ijms19061789 - 16 Jun 2018

Cited by 32 | Viewed by 4231

Abstract

MicroRNAs have recently been proposed as non-invasive biomarkers in Oral Squamous Cell Carcinoma (OSCC). The aim of this study was to analyze the expression of a panel of miRNAs in epithelial cells collected by oral brushing from OSCCs from regenerative areas after OSCC [...] Read more.

MicroRNAs have recently been proposed as non-invasive biomarkers in Oral Squamous Cell Carcinoma (OSCC). The aim of this study was to analyze the expression of a panel of miRNAs in epithelial cells collected by oral brushing from OSCCs from regenerative areas after OSCC surgical resection and from their respective normal distant mucosa. Oral brushing specimens were collected from 24 healthy donors, 14 OSCC patients with specimens from tumour and normal distant mucosa, and from 13 patients who had OSCC resection, with samples from regenerative areas after OSCC resection and normal distant mucosa. Expression levels of eight targets (miR-21, miR-375, miR-345, miR-181b, miR-146a, miR-649, miR-518b, and miR-191) were evaluated by real-time Polymerase Chain Reaction (PCR). A highly significant between-group difference was found for miR-21 (F = 6.58, p < 0.001), miR-146a (F = 6.974, p < 0.001), and miR-191 (F = 17.07, p < 0.001). The major difference was observed between samples from healthy donors and from OSCC brushing, whereas no significant differences were observed between areas infiltrated by OSCC and their respective normal distant mucosa. Furthermore, altered expression of miR-146a and miR-191 was also observed in regenerative areas after OSCC resection. Conclusions: Oral brushing could be proposed as a noninvasive method to study microRNA expression in oral mucosa in OSCC patients. Full article

(This article belongs to the Special Issue Head and Neck Cancers: Diagnostic, Prognostic and Predictive Biomarkers)

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15 pages, 4801 KiB

Open AccessArticle

Identification of Differentially Expressed Genes Induced by Aberrant Methylation in Oral Squamous Cell Carcinomas Using Integrated Bioinformatic Analysis

by Xiaoqi Zhang, Hao Feng, Dongfang Li, Shanshan Liu, Norio Amizuka and Minqi Li

Int. J. Mol. Sci. 2018, 19(6), 1698; https://doi.org/10.3390/ijms19061698 - 07 Jun 2018

Cited by 29 | Viewed by 5916

Abstract

Oral squamous cell carcinoma (OSCC) is a malignant disease. Methylation plays a key role in the etiology and pathogenesis of OSCC. The goal of this study was to identify aberrantly methylated differentially expressed genes (DEGs) in OSCCs, and to explore the underlying mechanisms [...] Read more.

Oral squamous cell carcinoma (OSCC) is a malignant disease. Methylation plays a key role in the etiology and pathogenesis of OSCC. The goal of this study was to identify aberrantly methylated differentially expressed genes (DEGs) in OSCCs, and to explore the underlying mechanisms of tumorigenesis by using integrated bioinformatic analysis. Gene expression profiles (GSE30784 and GSE38532) were analyzed using the R software to obtain aberrantly methylated DEGs. Functional enrichment analysis of screened genes was performed using the DAVID software. Protein–protein interaction (PPI) networks were constructed using the STRING database. The cBioPortal software was used to exhibit the alterations of genes. Lastly, we validated the results with the Cancer Genome Atlas (TCGA) data. Twenty-eight upregulated hypomethylated genes and 24 downregulated hypermethylated genes were identified. These genes were enriched in the biological process of regulation in immune response, and were mainly involved in the PI3K-AKT and EMT pathways. Additionally, three upregulated hypomethylated oncogenes and four downregulated hypermethylated tumor suppressor genes (TSGs) were identified. In conclusion, our study indicated possible aberrantly methylated DEGs and pathways in OSCCs, which could improve the understanding of the underlying molecular mechanisms. Aberrantly methylated oncogenes and TSGs may also serve as biomarkers and therapeutic targets for the precise diagnosis and treatment of OSCCs in the future. Full article

(This article belongs to the Special Issue Head and Neck Cancers: Diagnostic, Prognostic and Predictive Biomarkers)

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11 pages, 1659 KiB

Open AccessArticle

The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous Cell Carcinoma

by Shau-Hsuan Li, Hung-I Lu, Wan-Ting Huang, Wan-Yu Tien, Ya-Chun Lan, Wei-Che Lin, Hsin-Ting Tsai and Chang-Han Chen

Int. J. Mol. Sci. 2018, 19(1), 297; https://doi.org/10.3390/ijms19010297 - 19 Jan 2018

Cited by 16 | Viewed by 4254

Abstract

The dysregulation of the ubiquitously transcribed TPR gene on the X chromosome (UTX) has been reported to be involved in the oncogenesis of several types of cancers. However, the expression and significance of UTX in esophageal squamous cell carcinoma (ESCC) remains [...] Read more.

The dysregulation of the ubiquitously transcribed TPR gene on the X chromosome (UTX) has been reported to be involved in the oncogenesis of several types of cancers. However, the expression and significance of UTX in esophageal squamous cell carcinoma (ESCC) remains largely undetermined. Immunohistochemistry was performed in 106 ESCC patients, and correlated with clinicopathological features and survival. The functional role of UTX in ESCC cells was determined by UTX-mediated siRNA. Univariate analyses showed that high UTX expression was associated with superior overall survival (OS, p = 0.011) and disease-free survival (DFS, p = 0.01). UTX overexpression was an independent prognosticator in multivariate analysis for OS (p = 0.013, hazard ratio = 1.996) and DFS (p = 0.009, hazard ratio = 1.972). The 5-year OS rates were 39% and 61% in patients with low expression and high expression of UTX, respectively. Inhibition of endogenous UTX in ESCC cells increased cell viability and BrdU incorporation, and decreased the expression of epithelial marker E-cadherin. Immunohistochemically, UTX expression was also positively correlated with E-cadherin expression. High UTX expression is independently associated with a better prognosis in patients with ESCC and downregulation of UTX increases ESCC cell growth and decreases E-cadherin expression. Our results suggest that UTX may be a novel therapeutic target for patients with ESCC. Full article

(This article belongs to the Special Issue Head and Neck Cancers: Diagnostic, Prognostic and Predictive Biomarkers)

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Review

Jump to: Research, Other

15 pages, 561 KiB

Open AccessReview

The Promise of Novel Biomarkers for Head and Neck Cancer from an Imaging Perspective

by Loredana G. Marcu, Paul Reid and Eva Bezak

Int. J. Mol. Sci. 2018, 19(9), 2511; https://doi.org/10.3390/ijms19092511 - 24 Aug 2018

Cited by 18 | Viewed by 3454

Abstract

It is an agreed fact that overall survival among head and neck cancer patients has increased over the last decade. Several factors however, are still held responsible for treatment failure requiring more in-depth evaluation. Among these, hypoxia and proliferation-specific parameters are the main [...] Read more.

It is an agreed fact that overall survival among head and neck cancer patients has increased over the last decade. Several factors however, are still held responsible for treatment failure requiring more in-depth evaluation. Among these, hypoxia and proliferation-specific parameters are the main culprits, along with the more recently researched cancer stem cells. This paper aims to present the latest developments in the field of biomarkers for hypoxia, stemness and tumour proliferation, from an imaging perspective that includes both Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) as well as functional magnetic resonance imaging (MRI). Quantitative imaging of biomarkers is a prerequisite for accurate treatment response assessment, bringing us closer to the highly needed personalised therapy. Full article

(This article belongs to the Special Issue Head and Neck Cancers: Diagnostic, Prognostic and Predictive Biomarkers)

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9 pages, 6526 KiB

Open AccessCase Report

HPV Virus Transcriptional Status Assessment in a Case of Sinonasal Carcinoma

by Gennaro Ilardi, Daniela Russo, Silvia Varricchio, Giovanni Salzano, Giovanni Dell’Aversana Orabona, Virginia Napolitano, Rosa Maria Di Crescenzo, Alessandra Borzillo, Francesco Martino, Francesco Merolla, Massimo Mascolo and Stefania Staibano

Int. J. Mol. Sci. 2018, 19(3), 883; https://doi.org/10.3390/ijms19030883 - 16 Mar 2018

Cited by 4 | Viewed by 3166

Abstract

Human Papilloma Virus (HPV) can play a causative role in the development of sinonasal tract malignancies. In fact, HPV may be the most significant causative agent implicated in sinonasal tumorigenesis and is implicated in as many as 21% of sinonasal carcinomas. To date, [...] Read more.

Human Papilloma Virus (HPV) can play a causative role in the development of sinonasal tract malignancies. In fact, HPV may be the most significant causative agent implicated in sinonasal tumorigenesis and is implicated in as many as 21% of sinonasal carcinomas. To date, there are no definitive, reliable and cost-effective, diagnostic tests approved by the FDA for the unequivocal determination of HPV status in head and neck cancers. We followed an exhaustive algorithm to correctly test HPV infection, including a sequential approach with p16INK4a IHC, viral DNA genotyping and in situ hybridization for E6/E7 mRNA. Here, we report a case of sinonasal carcinoma with discordant results using HPV test assays. The tumor we describe showed an irregular immunoreactivity for p16INK4a, and it tested positive for HPV DNA; nevertheless, it was negative for HR-HPV mRNA. We discuss the possible meaning of this discrepancy. It would be advisable to test HPV transcriptional status of sinonasal carcinoma on a diagnostic routine basis, not only by p16INK4a IHC assay, but also by HPV DNA genotyping and HR-HPV mRNA assessment. Full article

(This article belongs to the Special Issue Head and Neck Cancers: Diagnostic, Prognostic and Predictive Biomarkers)

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