Biomarkers in saliva for the detection of oral squamous cell carcinoma and their potential use for early diagnosis: a systematic review

Abstract

Objective To determine the capacity of salivary biomarkers in the early diagnosis of oral squamous cell carcinoma. Study design A systematic review of the literature was performed based on the English titles listed in the PubMed, EBSCO, Cochrane, Science Direct, ISI web Science and SciELO databases using the following search descriptors: Oral cancer, diagnosis, biomarkers, saliva and oral squamous cell carcinoma. Abstracts and full-text articles were assessed independently by two reviewers. International checklists for assessment of methodological quality were used. Levels of evidence and grades of recommendation through the Scottish Intercollegiate Guidelines Network (SIGN) template were recognized. The units of analysis were identified through a reference matrix. Results Through the research strategy and after application of different filters and considering choosing criteria, six studies were obtained for analysis. Salivary biomarkers for oral cancer most frequently found were mRNA and proteins for IL-8, CD44, MMP-1 and MMP-3. New peptide-biomarkers such as Cyfra 21-1 and ZNF510 were found. ZNF 510 was the only biomarker which increased in the population with tumour stage T1 + T2 and T3 + T4. Only one study showed a sensitivity and specificity of 96% when the biomarker ZNF 510 is employed to discriminate early and late tumour stages. Conclusions There is no sufficient scientific evidence to support the capacity of the identified salivary biomarkers for the early diagnosis of oral cancer (sub-clinical stages of the pathogenic period before cancer phenotypes are manifested). Salivary biomarkers, however, may be employed to discriminate between healthy and cancer patients.

Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer

“…Saliva has direct contact with OSCC lesions, which gives it particular potential as a specific and sensitive screening tool. While more than 100 potential salivary biomarkers (DNA, RNA, mRNA, miRNA, and protein) have been previously identified for OSCC (reviewed in [5][6][7][8]), further research is required to validate biomarkers for clinical applications.…”

The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseases

“…The time-dependent maximal inhibitory concentration of EGCG is 52.3 uM in the SSC-4 cells. EGCG treatment (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [ 37 , 38 ]. The main ROS coming from mitochondria played a crucial role in apoptosis and autophagy.…”

CYFRA 21-1 and MMP-9 as salivary biomarkers for the detection of oral squamous cell carcinoma: a systematic review of diagnostic test accuracy

“…Saliva contains an extensive number of compounds, is safe to handle and store, does not clot, and as such, it is deemed a promising diagnostic biofluid 4 . Two systematic reviews have evaluated the performance of a wide range of salivary biomarkers (biomarker expression) in OSCC 5,6 . However, these systematic reviews mainly included 'casecontrol' type accuracy studies, which can be prone to bias.…”

“…(4) Two systematic reviews have evaluated the performance of a wide range of salivary biomarker expression in OSCC. (5,6) However, these systematic reviews mainly included 'case-control' type accuracy studies, which can be prone to bias. Studies which compare altered expression of a specific salivary biomarker in 'cases' with OSCC with those in healthy 'control' participants can deliver misleading results when the methods of participant recruitment are not taken into consideration (7).…”