Biomarkers of progression to oral cancer in patients with dysplasia: A systematic review

Abstract

Identifying oral dysplastic lesions with a high risk of malignant transformation may create opportunities for early therapeutic interventions. Several tissue biomarkers have been suggested to date as prognostic indicators of the progression of dysplastic lesions to oral cancer. We herein present a systematic review (PROSPERO CRD42018086476), with the aim of identifying, evaluating and summarizing evidence on prognostic biomarkers of progression to oral cancer in patients with dysplasia. A search through MEDLINE/PubMed and Scopus databases was performed. The review only included primary articles that reported risk values associated with malignancy after a multivariate analysis. The quality of the findings was analyzed using the Reporting Recommendations for Tumor Marker Prognostic Studies, and research trends were established using SciCurve Open. A total of 4 potential biomarkers were identified: Degree of dysplasia, and the proteins retinal dehydrogenase 1, prominin-1 and podoplanin. All 3 protein biomarkers have been recognized as cancer stem cell markers. The studies were of acceptable quality, although none included sample size determinations. Due to the lack of validation and follow-up studies, these biomarkers are considered to be in a discovery phase and require validation by prospective clinical trials. The present analysis indicated that there are currently insufficient data to include these biomarkers in the clinical decision-making process.

Human Papilloma Virus and Cancer Stem Cell markers in Oral Epithelial Dysplasia—An Immunohistochemical Study

“…42 Considering that this protein is not present at high levels in the oral mucosa, ALDH1 may represent a therapeutic opportunity for preventing the progression to oral cancer in patients with dysplasia. 43 In the present of OED cases had positive ALDH1 expression, unlike the findings of Liu et al and Visus et al where ALDH1 expression was found in only 38.3% and 32.5% of OED patients, respectively. 44,45 This suggests the role of ALDH1 in the stepwise transformation of OED to carcinomas, since various studies have suggested that ALDH1 expression is a predictive marker for the malignant transformation of OED.…”

Differential Expression of Potential Biomarkers of Oral Squamous Cell Carcinoma Development

“…3 Graphic representation of survivin, CDKN2A, EGFR, PLK1, p63, p40, CCND1 and BCL2 protein expression in comparison with low-and high-grade dysplasia who showed that about 50% of premalignant lesions had survivin overexpression [39]. The identification of lesions with an increased risk of transformation to oral cancer remains a clinical struggle, which, if resolved, would improve early interventions, reducing cancer-related mortality and morbidity [40]. Thus, the changes that a normal cell undergoes as it becomes malignant area matter of great interest.…”

The Expression of Methyltransferase-Like 3 in Oral Precancerous Lesions and Oral Squamous Cell Carcinoma

“…3 Despite the progress in cancer diagnosis and surgical treatment, the 5-year survival rate of OSCCs remains unfavorable ($50%). 5 Thus, identifying reliable biomarkers to classify oral dysplastic lesions with a high risk of malignant transformation would establish opportunities for early therapeutic interventions. 5 Epigenetic alterations, such as DNA and RNA methylation, histone protein modification, and microRNA dysregulation, have been reported to contribute to the tumorigenesis of OSCCs.…”

“…5 Thus, identifying reliable biomarkers to classify oral dysplastic lesions with a high risk of malignant transformation would establish opportunities for early therapeutic interventions. 5 Epigenetic alterations, such as DNA and RNA methylation, histone protein modification, and microRNA dysregulation, have been reported to contribute to the tumorigenesis of OSCCs. 6 N6-methyladenosine (m6A), methylated at the N6 position of adenosine, is one of the most common and abundant RNA modifications in humans.…”