The Connection between MicroRNAs and Oral Cancer Pathogenesis: Emerging Biomarkers in Oral Cancer Management

Oral cancer is a common human malignancy that still maintains an elevated mortality rate despite scientific progress. Tumorigenesis is driven by altered gene expression patterns of proto-oncogenes and tumor-suppressor genes. MicroRNAs, a class of short non-coding RNAs involved in gene regulation, seem to play important roles in oral cancer development, progression, and tumor microenvironment modulation. As properties of microRNAs render them stable in diverse liquid biopsies, together with their differential expression signature in cancer cells, these features place microRNAs at the top of promising biomarkers for diagnostic and prognostic values. In this review, we highlight eight expression levels and functions of the most relevant microRNAs involved in oral cancer development, progression, and microenvironment sustainability. Furthermore, we emphasize the potential of using these small RNA species as non-invasive biomarkers for the early detection of oral cancerous lesions. Conclusively, we highlight the perspectives and limitations of microRNAs as novel diagnostic tools, as well as therapeutic models.

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Podoplanin: A Novel Marker for Oral Cancer Risk in Patients With Oral Premalignancy

Journal of Clinical Oncology ◽

10.1200/jco.2007.13.4072 ◽

2008 ◽

Vol 26 (3) ◽

pp. 354-360 ◽

Cited By ~ 126

Author(s):

Hidetoshi Kawaguchi ◽

Adel K. El-Naggar ◽

Vali Papadimitrakopoulou ◽

Hening Ren ◽

You-Hong Fan ◽

...

Keyword(s):

Oral Cancer ◽

Cancer Risk ◽

Expression Patterns ◽

Oral Lesion ◽

Cancer Development ◽

Long Term Follow Up ◽

Podoplanin Expression ◽

Clinicopathologic Parameters ◽

Oral Cancer Risk

Purpose Oral leukoplakia (OPL) is a heterogeneous oral lesion with an increased oral cancer risk. Current clinical parameters cannot predict the potential of malignant transformation in patients with OPL. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in oral cancer and some oral premalignancies. The purpose of this study is to determine a role of podoplanin in predicting oral cancer development in patients with OPL. Patients and Methods Podoplanin expression was determined in 150 OPL patients with long-term follow-up using immunohistochemistry. Association between the protein expression patterns and clinicopathologic parameters including oral cancer development during the follow-up were analyzed. Results Fifty-six (37%) of the 150 OPL patients exhibited podoplanin expression in the basal and suprabasal layers and were classified as podoplanin positive. Podoplanin positivity was more frequent in older patients (P = .016), females (P = .020), and dysplastic lesions (P = .040). Patients with OPL that was podoplanin positive had significantly higher incidence of oral cancer than did those whose OPL was podoplanin negative (P = .0002). In the multivariate analysis using histology and podoplanin as cofactors, podoplanin was the only independent factor for oral cancer development (hazard ratio = 3.087; 95% CI, 1.530 to 6.231; P = .002). Importantly, oral cancer risk can be further stratified by considering both histology and podoplanin information. Conclusion Podoplanin is frequently expressed in OPL. Together with histology, podoplanin may serve as a powerful biomarker to predict the risk for oral cancer development in patients with OPL.

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Circulating Long Non-Coding RNAs as Novel Potential Biomarkers for Osteogenic Sarcoma

Cancers ◽

10.3390/cancers13164214 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4214

Author(s):

Sutpirat Moonmuang ◽

Parunya Chaiyawat ◽

Salinee Jantrapirom ◽

Dumnoensun Pruksakorn ◽

Luca Lo Piccolo

Keyword(s):

Clinical Decision Making ◽

Expression Patterns ◽

Osteogenic Sarcoma ◽

Clinical Decision ◽

Diagnostic Tools ◽

Liquid Biopsies ◽

Specific Expression ◽

Altered Expression ◽

Novel Biomarkers ◽

Non Coding Rnas

Circulating cell-free nucleic acids recently became attractive targets to develop non-invasive diagnostic tools for cancer detection. Along with DNA and mRNAs, transcripts lacking coding potential (non-coding RNAs, ncRNAs) directly involved in the process of tumor pathogenesis have been recently detected in liquid biopsies. Interestingly, circulating ncRNAs exhibit specific expression patterns associated with cancer and suggest their role as novel biomarkers. However, the potential of circulating long ncRNAs (c-lncRNAs) to be markers in osteosarcoma (OS) is still elusive. In this study we performed a systematic review to identify thirteen c-lncRNAs whose altered expression in blood associate with OS. We herein discuss the potential impact that these c-lncRNAs may have on clinical decision-making in the management of OS. Overall, we aimed to provide novel insights that can contribute to the development of future precision medicine in oncology.

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Detection of EBV Infection and Gene Expression in Oral Cancer from Patients in Taiwan by Microarray Analysis

Journal of Biomedicine and Biotechnology ◽

10.1155/2009/904589 ◽

2009 ◽

Vol 2009 ◽

pp. 1-15 ◽

Cited By ~ 9

Author(s):

Ching-Yu Yen ◽

Min-Chi Lu ◽

Ching-Cherng Tzeng ◽

Jia-Yan Huang ◽

Hsueh-Wei Chang ◽

...

Keyword(s):

Gene Expression ◽

Oral Cancer ◽

Epstein Barr Virus ◽

Expression Patterns ◽

Viral Gene Expression ◽

Viral Gene ◽

Barr Virus ◽

Cancer Pathogenesis ◽

Epstein Barr

Epstein-Barr virus is known to cause nasopharyngeal carcinoma. Although oral cavity is located close to the nasal pharynx, the pathogenetic role of Epstein-Barr virus (EBV) in oral cancers is unclear. This molecular epidemiology study uses EBV genomic microarray (EBV-chip) to simultaneously detect the prevalent rate and viral gene expression patterns in 57 oral squamous cell carcinoma biopsies (OSCC) collected from patients in Taiwan. The majority of the specimens (82.5%) were EBV-positive that probably expressed coincidently the genes for EBNAs, LMP2A and 2B, and certain structural proteins. Importantly, the genes fabricated at the spots 61 (BBRF1, BBRF2, and BBRF3) and 68 (BDLF4 and BDRF1) on EBV-chip were actively expressed in a significantly greater number of OSCC exhibiting exophytic morphology or ulceration than those tissues with deep invasive lesions (P=.0265and .0141, resp.). The results may thus provide the lead information for understanding the role of EBV in oral cancer pathogenesis.

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The epigenetic potentials of dietary polyphenols in prostate cancer management

Biochemistry and Cell Biology ◽

10.1139/bcb-2012-0044 ◽

2013 ◽

Vol 91 (6) ◽

pp. 361-368 ◽

Cited By ~ 17

Author(s):

Ata Abbas ◽

William Patterson ◽

Philippe T. Georgel

Keyword(s):

Prostate Cancer ◽

Posttranslational Modifications ◽

Expression Patterns ◽

Tumor Biology ◽

Dietary Polyphenols ◽

Anticancer Properties ◽

Cancer Management ◽

Cancer Pathogenesis ◽

Causes And Risk Factors ◽

Prostate Cancer Management

Prostate cancer is a disease that is greatly affected by lifestyle, particularly diet, and is more prevalent in US and European countries compared with South and East Asia. Among several known causes and risk factors, nutrition plays an important role in prostate cancer pathogenesis. Various dietary components including polyphenols have been shown to possess anticancer properties. Dietary polyphenols have been the subject of extensive studies for the last decade because of their anticancer and chemopreventive potentials. Besides possessing various antitumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Various polyphenols have been shown to affect DNA methylation, histone posttranslational modifications, and microRNA expression patterns in prostate cancer. In this review, we discuss the contribution of dietary polyphenols to various epigenetic modifications in prostate cancer. Since prostate cancer and diet are intimately associated, polyphenol-rich diets that epigenetically modify tumor biology have great significance in the prevention and management of prostate cancer.

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Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer

Cellular Oncology ◽

10.1007/s13402-021-00626-9 ◽

2021 ◽

Author(s):

Chun Yang ◽

Stéphane Croteau ◽

Pierre Hardy

Keyword(s):

Histone Deacetylase ◽

Posttranslational Modifications ◽

Histone Deacetylases ◽

Muscle Development ◽

Target Genes ◽

Human Cancer ◽

Expression Patterns ◽

Aberrant Expression ◽

Physiological Processes ◽

Cancer Pathogenesis

Abstract Background HDAC9 (histone deacetylase 9) belongs to the class IIa family of histone deacetylases. This enzyme can shuttle freely between the nucleus and cytoplasm and promotes tissue-specific transcriptional regulation by interacting with histone and non-histone substrates. HDAC9 plays an essential role in diverse physiological processes including cardiac muscle development, bone formation, adipocyte differentiation and innate immunity. HDAC9 inhibition or activation is therefore a promising avenue for therapeutic intervention in several diseases. HDAC9 overexpression is also common in cancer cells, where HDAC9 alters the expression and activity of numerous relevant proteins involved in carcinogenesis. Conclusions This review summarizes the most recent discoveries regarding HDAC9 as a crucial regulator of specific physiological systems and, more importantly, highlights the diverse spectrum of HDAC9-mediated posttranslational modifications and their contributions to cancer pathogenesis. HDAC9 is a potential novel therapeutic target, and the restoration of aberrant expression patterns observed among HDAC9 target genes and their related signaling pathways may provide opportunities to the design of novel anticancer therapeutic strategies.

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Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

Life ◽

10.3390/life11070593 ◽

2021 ◽

Vol 11 (7) ◽

pp. 593

Author(s):

Srikanth Umakanthan ◽

Maryann M Bukelo

Keyword(s):

Epstein Barr Virus ◽

Diagnostic Tools ◽

Main Role ◽

Genetic Changes ◽

Barr Virus ◽

Cancer Pathogenesis ◽

Genomic Studies ◽

Epstein Barr ◽

Oncogenic Form

Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies. This article reviews the role of genetic changes in EBV-associated lymphomas and carcinomas. This includes the prolific molecular genesis, key diagnostic tools, and target-specific drugs that have been in recent clinical use.

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Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late

Diagnostics ◽

10.3390/diagnostics11010103 ◽

2021 ◽

Vol 11 (1) ◽

pp. 103

Author(s):

Maarten J. IJzerman ◽

Jasper de Boer ◽

Arun Azad ◽

Koen Degeling ◽

Joel Geoghegan ◽

...

Keyword(s):

Clinical Utility ◽

Clinical Laboratory ◽

Genomic Analysis ◽

Current Evidence ◽

Liquid Biopsies ◽

Blood Draw ◽

Minimum Quality Standards ◽

Cancer Management ◽

Alternative Funding ◽

And Performance

Blood-based liquid biopsies are considered a new and promising diagnostic and monitoring tool for cancer. As liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue biopsies. A multi-disciplinary workshop (n = 98 registrations) was organized to discuss routine implementation of liquid biopsies in cancer management. Real-time polls were used to engage with experts’ about the current evidence of clinical utility and the barriers to implementation of liquid biopsies. Clinical, laboratory and health economics presentations were given to illustrate the opportunities and current levels of evidence, followed by three moderated break-out sessions to discuss applications. The workshop concluded that tumor-informed assays using next-generation sequencing (NGS) or PCR-based genotyping assays will most likely provide better clinical utility than tumor-agnostic assays, yet at a higher cost. For routine application, it will be essential to determine clinical utility, to define the minimum quality standards and performance of testing platforms and to ensure their use is integrated into current clinical workflows including how they complement tissue biopsies and imaging. Early health economic models may help identifying the most viable application of liquid biopsies. Alternative funding models for the translation of complex molecular diagnostics, such as liquid biopsies, may also be explored if clinical utility has been demonstrated and when their use is recommended in multi-disciplinary consensus guidelines.

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A pilot study to establish non-invasive biomarkers for higher-grade meningioma

Neuro-Oncology ◽

10.1093/neuonc/noz167.023 ◽

2019 ◽

Vol 21 (Supplement_4) ◽

pp. iv6-iv6

Author(s):

Daniele Baiz ◽

Caterina Negroni ◽

Emanuela Ercolano ◽

Claire L Adams ◽

Kathreena M Kurian ◽

...

Keyword(s):

Ex Vivo ◽

Tumour Progression ◽

Primary Tumour ◽

Regulation Of Gene Expression ◽

Diagnostic Tools ◽

Malignant Tumours ◽

Liquid Biopsies ◽

Benign Meningioma ◽

Non Invasive ◽

Serum Exosomes

Abstract Introduction Meningioma brain tumours are the most common primary tumour in adults. Despite surgery and/or radiation therapy, meningioma may recur. The 5-year recurrence rate in benign meningioma is estimated in about 10% while much greater in atypical and malignant tumours. MicroRNAs (miRNAs) represent a large class of small RNAs driving regulation of gene expression and playing a role in tumour progression and therefore proposed as diagnostic tools. Moreover, miRNAs can be released from tumour cells into the blood stream via exosomes, showing potential to be used as liquid biopsies. Methods Identification of novel circulating biomarkers was conducted by performing an unbiased Cancer MicroRNA qPCR Array, followed by bioinformatics analysis. In parallel, we conducted a biased in silico analysis of the miRNAs targeting Cyclin D1 and E1, recently proposed as immunohistochemical meningioma biomarkers. Validation studies performed using TaqMan® reagents. Results Stringent unbiased (p<0.01) miRNA profiling followed by validation in ex vivo samples revealed that the miR-9-1 is upregulated in higher-grade meningioma tissues and serum exosomes, controlled by the EGFR/AP-1 axis and correlated with lower levels of E-Cadherin, a proposed biomarker for malignant meningioma. On the contrary, biased analysis, followed by validation in vitro and ex vivo, showed that the miR-497~195 cluster is downregulated in higher-grade meningioma tissues and serum exosomes, correlating with the overexpression of GATA-4, a novel meningioma tissue biomarker. Conclusion Our data demonstrated that both miR-497~195 and miR-9-1 show potential to become promising non-invasive biomarkers for higher-grade meningioma, reflecting their expression status in tissues. (DB and CN contributed equally).

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Concurrent Endometrial Intraepithelial Carcinoma (EIC) and Serous Ovarian Cancer: Can EIC Be Seen as the Precursor Lesion?

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182434a81 ◽

2012 ◽

Vol 22 (3) ◽

pp. 457-464 ◽

Cited By ~ 16

Author(s):

Thijs Roelofsen ◽

Léon C.L.T. van Kempen ◽

Jeroen A.W.M. van der Laak ◽

Maaike A. van Ham ◽

Johan Bulten ◽

...

Keyword(s):

Ovarian Cancer ◽

Estrogen Receptor ◽

Progesterone Receptor ◽

Expression Patterns ◽

Neoplastic Progression ◽

Precursor Lesion ◽

Ki 67 ◽

Cancer Management ◽

Ploidy Analysis ◽

Intraepithelial Carcinoma

ObjectiveThe pathogenesis of serous ovarian carcinoma (SOC) is still unknown. Recently, endometrial intraepithelial carcinoma (EIC) was proposed to be the precursor lesion of SOC. This study examines the model of EIC as precursor for SOC.MethodsCases of SOC with a noninvasive or superficially invasive serous lesion, a hyperplastic lesion with/without atypia, or EIC in the endometrium were selected for inclusion in this study. Tissue sections from both ovaries, the fallopian tubes, and the uterus were extensively reviewed by an expert gynecopathologist. For both EIC and SOC, immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor; TP53 mutation analysis; and in situ ploidy analysis were performed.ResultsNine cases of SOC with concurrent EIC in the endometrium were identified. Immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor revealed almost identical expression patterns and similar intensities in each pair of EIC and coincident SOC. Identical TP53 mutations were found in SOC and coinciding EIC in 33% of the cases, suggesting a clonal origin. DNA ploidy analysis, as a marker for neoplastic progression, demonstrated an increased number of aneuploid nuclei in SOC compared to their corresponding EIC (P = 0.039). In addition, the mean amount of DNA per nucleus in SOC was higher (ie, more aneuploid) compared to EIC (P = 0.039).ConclusionThis study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.

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