Molecular Signatures of Tumour and Its Microenvironment for Precise Quantitative Diagnosis of Oral Squamous Cell Carcinoma: An International Multi-Cohort Diagnostic Validation Study

Abstract

Background: Heterogeneity in oral potentially malignant disorder (OPMD) poses a problem for accurate prognosis that impacts on treatment strategy and patient outcome. A holistic assessment based on gene expression signatures from both the tumour cells and their microenvironment is necessary to provide a more precise prognostic assessment than just tumour cell signatures alone. Methods: We reformulated our previously established multigene qPCR test, quantitative Malignancy Index Diagnostic System (qMIDS) with new genes involved in matrix/stroma and immune modulation of the tumour microenvironment. An algorithm calculates and converts a panel of 16 gene mRNA expression levels into a qMIDS index to quantify risk of malignancy for each sample. Results: The new qMIDSV2 assay was validated in a UK oral squamous cell carcinoma (OSCC) cohort (n = 282) of margin and tumour core samples demonstrating significantly better diagnostic performance (AUC = 0.945) compared to previous qMIDSV1 (AUC = 0.759). Performance of qMIDSV2 were independently validated in Chinese (n = 35; AUC = 0.928) and Indian (n = 95; AUC = 0.932) OSCC cohorts. Further, 5-year retrospective analysis on an Indian dysplastic lesion cohort (n = 30) showed that qMIDSV2 was able to significantly differentiate between lesions without transformation and those with malignant transformation. Conclusions: This study validated a novel multi-gene qPCR test on a total of 535 tissue specimens from UK, China and India, demonstrating a rapid minimally invasive method that has a potential application for dysplasia risk stratification. Further study is required to establish if qMIDSV2 could be used to improve OPMD patient management, guide treatment strategy and reduce oral cancer burden.

Personalized Medicine in Oral Oncology: Imaging Methods and Biological Markers to Support Diagnosis of Oral Squamous Cell Carcinoma (OSCC): A Narrative Literature Review

“…We encourage further multicentric and comprehensive studies and hope that they will allow us to reach this critical goal by excluding a holistic approach and considering a multivariate analysis of the co-occurring biological, histological, metabolic, and microbiological changes occurring in cancerogenesis or proposing digital-supported analyses of big data or algorithms, through procedures or sample collections with low invasiveness. This is the case offered by the promising results from the study by The et al [ 239 ], who recently assessed the quantitative Malignancy Index Diagnostic System (qMIDS) based on a multigene RT-qPCR method for the contemporary detection of a series of genes involved in cancerogenesis and immune dysregulations occurring during cancer, from tiny 1 mm 3 minimally invasive biopsies.…”

Salivary Metabolomics for Oral Cancer Detection: A Narrative Review

“…The relationship between the study design and cohort is depicted in Figure 3 . Multigene expression test for OSCC was established based on diagnostic performance in a multi-institute evaluation in three countries [ 81 ]. Such large-scale validation is required for salivary metabolomics; however, two obstacles exist.…”

Oral Field Cancerization: A Review with Case Reports

“…Genetic Basis: Mutations in YAP1, WWTR1, p75NTR, NFKB2, POLR2A [14,15] in a single cell was considered to be initial step that triggers the process, the mutant cell then proliferates into a clonal unit and then into a patch of mutated cells. This field eventually replaces the normal tissues.…”