LGR5 expression in oral epithelial dysplasia and oral squamous cell carcinoma

Dalley, Andrew J.; Majeed, Ahmad Abdul; Pitty, Luke P.; Major, Aidan G.; Farah, Camile S.

doi:10.1016/j.oooo.2014.11.014

Cited by 18 publications

(10 citation statements)

References 18 publications

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“…Numerous studies have compared the biological properties of premalignant lesions with their malignant potential; to this end, the expression of some biomarkers in oral precancerous and cancerous lesions have been compared. 6,23,[25][26][27][28] The molecular events that cause a premalignant lesion to turn into a carcinoma are still unknown, and it is still impossible to predict which premalignant lesion will progress to carcinoma. 29 …”

Section: Resultsmentioning

confidence: 99%

The Evaluation of Ghrelin Expression In Oral Leukoplakia And Oral Squamous Cell Carcinoma: An Immunohistochemical Study

Fikirli¹,

Özeç²,

Eğılmez³

et al. 2017

EÜ Dişhek Fak Derg

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ÖZET AMAÇ: Biobelirteçler normal dokuda, prekanseröz lezyonlarda ve kanserli dokuda farklı miktarlarda bulunabilen proteinler veya genlerdir, biobelirteçlerin değerlendirilmesi daha etkin bir şekilde malign transformasyon öngörüsü yapılmasını sağlayabilir. Bu çalışmanın amacı normal oral epitel, oral lökoplaki ve oral skuamoz hücreli karsinomada (OSHK) ghrelin seviyelerinin araştırılarak karşılaştırılmasıdır. YÖNTEM: Patoloji bölümü arşivinden elde edilen toplam 55 adet daha önce tanısı konulmuş normal oral mukoza (n = 15), oral lökoplaki (n = 18) ve OSHK (n = 22) bloklarından deparafinize edilerek elde edilen preparatlar özel antikorlar kullanılarak immünhistokimyasal olarak boyanmış ve ghrelin seviyeleri değerlendirilmiştir. İmmünhistokimyasal boyamada ghrelin mevcudiyeti mikroskop altında 100 hücre değerlendirilerek sayısallaştırılmıştır. Ghrelin pozitif hücrelerde kahverengi sitoplazmik boyama görülmüştür. BULGULAR: Normal oral mukozada hücrelerinin % 64'ünde, oral lökoplaki hücrelerinin % 66'sında ghrelin pozitif boyama görülürken, OSHK'da bu boyama yalnızca hücrelerin % 8'inde olmuştur. Diğer gruplar ile karşılaştırıldığı zaman OSHK grubunda ghrelin pozitif boyalı hücre miktarının istatistiksel olarak anlamlı şekilde az olduğu görülmüştür (P < 0.05). SONUÇ: Normal oral mukoza ve oral lökoplaki ile karşılaştırıldığı zaman OSHK grubunda ghrelin seviyesinin daha az olduğu tespit edilmiştir. Oral lökoplaki ve normal oral mukoza gruplarının ghrelinin seviyelerinin benzer olduğu belirlenmiştir. Oral karsinogenezis ile birlikte oluşan ghrelin seviyesinde ki değişikliklerin artmış malign potansiyelin belirlenmesinde bir biobelirteç olabileceği düşünülmektedir.

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Section: Resultsmentioning

confidence: 99%

The Evaluation of Ghrelin Expression In Oral Leukoplakia And Oral Squamous Cell Carcinoma: An Immunohistochemical Study

Fikirli¹,

Özeç²,

Eğılmez³

et al. 2017

EÜ Dişhek Fak Derg

View full text Add to dashboard Cite

show abstract

“…Furthermore, only the LGR5Δ5 splice variant but not LGR5FL or LGR5Δ8 mRNA level have a prognostic value for OSCC patients. In contrast another study in OSCC showed that the LGR5 expression increased during the process of the malignant transformation but there was no association between the LGR5 protein expression and other clinical parameters [22]. However, these investigators performed LGR5 immunohistochemistry and therefore a discrimination between splice variant products of LGR5 was not possible.…”

Section: Discussionmentioning

confidence: 99%

“…LGR5 was found to be overexpressed in colorectal cancer [14–18] and several studies indicated that LGR5 expression is associated with colorectal carcinogenesis, tumor growth and metastasis [18–20]. Subsequent studies demonstrated that LGR5 is expressed by a diverse range of adult tissues and organs and acts as a biomarker for adult stem cells in certain tissues including oral tissues [21, 22]. Furthermore, LGR5 was found to be overexpressed in several carcinomas having a close association with initiation and recurrence of different cancer types and correlating with tumor growth, invasion and poor prognosis [18, 20, 23, 24].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the LGR5 protein expression was investigated by immunohistochemistry (IHC) in OSCC, demonstrating an increased LGR5 expression correlating with disease severity but not with patient’s outcome [22]. In a previous work our group demonstrated the mRNA expression of the LGR5 transcript variant LGR5Δ5 , but not the expression of full length LGR5 ( LGR5FL ) being an independent unfavourable prognostic marker for soft tissue sarcoma patients (STS) [26].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic impact of mRNA levels of LGR5 transcript variants in OSCC patients

et al. 2019

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Background The human leucine-rich, repeat-containing G protein-coupled receptor 5 ( LGR5 ) is a stem cell marker in numerous adult tissues and is overexpressed in a large number of human carcinoma including colon cancer, breast cancer and oral squamous cell carcinomas (OSCC). The role of the full length transcript ( LGR5FL ) in progression and prognosis of several cancers was reported. However, the biological function of three splice variants of LGR5 ( LGR5Δ5 , LGR5Δ8 and LGR5Δ5–8 ) has yet to be thoroughly investigated. Methods Seventy-eight frozen tumor samples from adult OSCC patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of full length LGR5 , the splice variant of LGR5 lacking exon 5 ( LGR5Δ5 ), the splice variant of LGR5 lacking exon 8 ( LGR5Δ8 ) and the mRNA level of all known transcript variants together ( LGR5all ) were quantified and correlated to overall and disease-specific survival of OSCC patients, clinical parameters and the mRNA level of different tumor-associated markers. Results An elevated level of tumoral LGR5Δ5 mRNA, but not LGR5FL, LGR5Δ8 or LGR5all mRNA was significantly associated with a poor prognosis for the overall and disease-specific survival of OSCC patients (hazard ratio (HR) = 2.0; p = 0.02; 95% CI: 1.1–3.7; HR = 3.2; p = 0.01; 95% CI: 1.3–8.0; multivariable Cox regression), respectively. Additionally, a higher tumoral level of LGR5Δ5 mRNA in primary tumors was associated with the occurrence of regional lymph node metastases in OSCC patients (odds ratio (OR) = 3.1; p = 0.022; 95% CI: 1.2–7.9; binary logistic regression). Furthermore, the mRNA levels of all investigated LGR5 transcript variants were significantly correlated with the mRNA expression of Wnt-target genes and markers of epithelial-to-mesenchymal transition (EMT). Conclusion The mRNA level of the LGR5 splice variant LGR5Δ5 is an independent negative prognostic marker for overall and disease-specific survival and metastasis in OSCC patients. Additionally, we suggest, all LGR5 transcript variants are involved in the EMT process mainly through activating the Wnt-signalling pathway.

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“…LGR5 is the receptor for proteins of the R-spondin family, which synergize with Wnt ligands in the stimulation of the Wnt/β-catenin pathway and play a role in adult stem cell regulation. The expression of LGR5 was increased in oral dysplasia and oral carcinoma [98]. On the other hand, the phenotype of cancer stem-like cells derived from HNSCC patients was associated with c-MET receptor-dependent activation of canonical Wnt signaling.…”

Section: Functional Significance Of Wnt/β-catenin Pathway Dysregulationmentioning

confidence: 95%

The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

Paluszczak

2020

Cells

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The knowledge about the molecular alterations which are found in head and neck squamous cell carcinomas (HNSCC) has much increased in recent years. However, we are still awaiting the translation of this knowledge to new diagnostic and therapeutic options. Among the many molecular changes that are detected in head and neck cancer, the abnormalities in several signaling pathways, which regulate cell proliferation, cell death and stemness, seem to be especially promising with regard to the development of targeted therapies. Canonical Wnt signaling is a pathway engaged in the formation of head and neck tissues, however it is not active in adult somatic mucosal cells. The aim of this review paper is to bring together significant data related to the current knowledge on the mechanisms and functional significance of the dysregulation of the Wnt/β-catenin pathway in head and neck tumors. Research evidence related to the role of Wnt signaling activation in the stimulation of cell proliferation, migration and inhibition of apoptosis in HNSCC is presented. Moreover, its role in promoting stemness traits in head and neck cancer stem-like cells is described. Evidence corroborating the hypothesis that the Wnt signaling pathway is a very promising target of novel therapeutic interventions in HNSCC is also discussed.Cells 2020, 9, 723 2 of 20 blocking the interaction between PD-1 receptor and PD-L1, may be beneficial in patients with advanced, metastatic or recurrent HNSCC [7]. However, other therapeutic options are also necessary for the better clinical management of HNSCC patients. To that end, molecular alterations observed in HNSCC need to be studied in detail, in order to point to promising drug targets. Mechanisms of Wnt/β-Catenin Pathway Activation in HNSCCRecent genomic analyses have shown the prevalence of genetic driver alterations in HNSCC, which most frequently affect genes associated with receptor tyrosine kinase (e.g., EGFR, MET, KIT), PI3K, p53, Notch or Hippo signaling pathways. On the other hand, genetic alterations in genes related to canonical Wnt signaling were rarely detected in HNSCC [8,9]. In contrast to colorectal cancers, which show molecular alterations driving Wnt signaling activation in around 90% of cases [9], HNSCC were shown to lack CTNNB1 mutations and APC mutations were present infrequently [10][11][12][13][14][15][16]. The mutations of FAT1 tumor suppressor, which encodes a protocadherin protein that binds and inactivates β-catenin, were detected in some cases of HNSCC [17]. However, the activation of the Wnt/β-catenin pathway in HNSCC seems to be more prevalent than it is suggested by genetic findings, due to cross-talk with other molecular alterations, which can lead to pathway cross-activation. Indeed, it has been shown that β-catenin can be activated via enhanced EGFR or PI3K signaling, which belong to the most frequently dysregulated signaling pathways in HNSCC. In this regard, elevated EGFR expression was associated with delocalized β-catenin expression [13]. In another study, the nuclear ...

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LGR5 expression in oral epithelial dysplasia and oral squamous cell carcinoma

Cited by 18 publications

References 18 publications

The Evaluation of Ghrelin Expression In Oral Leukoplakia And Oral Squamous Cell Carcinoma: An Immunohistochemical Study

The Evaluation of Ghrelin Expression In Oral Leukoplakia And Oral Squamous Cell Carcinoma: An Immunohistochemical Study

Prognostic impact of mRNA levels of LGR5 transcript variants in OSCC patients

The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

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