Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer

Abstract

We evaluated potential biomarkers in human whole saliva for the early diagnosis of oral squamous cell carcinoma (OSCC). We selected 30 candidate genes with relevance to cancer from recent reports in PubMed. Saliva samples were obtained from 34 non-tumor control and 33 OSCC patients. Real-time PCR was performed, and mRNA levels were compared. Normalized mRNA levels of six genes (NGFI-A binding protein 2 (NAB2), cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1), nuclear pore complex interacting protein family, member B4 (NPIPB4), monoamine oxidase B (MAOB), sialic acid acetyltransferase (SIAE), and collagen, type III, alpha 1 (COL3A1)) were significantly lower in saliva of OSCC patients. Receiver operating characteristics (ROC) analysis was used to individually evaluate the predictive power of the potential biomarkers for OSCC diagnosis. The area under the curve (AUC) values were evaluated for the OSCC vs. non-tumor groups via univariate ROC analyses, as well as multivariate ROC analyses of combinations of multiple potential biomarkers. The combination of CYP27A1 + SIAE showed a favorable AUC value of 0.84. When we divided saliva samples into two groups according to age using a 60-year cut-off, with OSCC patients and controls evaluated together, the AUC of MAOB–NAB2 was more predictive of OSCC in the under-60 group (AUC, 0.91; sensitivity, 0.92; and specificity, 0.86) than any other gene combination. These results are expected to aid the early diagnosis of OSCC, especially in patients under 60 years of age. While more studies with larger numbers of patients are necessary, our result suggest that salivary mRNA would be a potent biomarker for early OSCC diagnosis.

Differential CircRNA Expression Signatures May Serve as Potential Novel Biomarkers in Prostate Cancer

“…The up-regulated hsa_circ_0000361 (FC 19.2, p < 0.001) is an exonic circRNA located on chromosome 11 and is associated with the gene SIAE ( Table 3 ). mRNA expression of SIAE has previously been shown to be reduced in patients with cancer ( Oh et al, 2020 ). We identified three circRNAs associated with the parental gene Caprin1 (hsa_circ_0021652, hsa_circ_0000288, and hsa_circ_0021647).…”

Mock clinical testing in the validation of fluid‐phase biomarkers for head and neck carcinoma diagnosis: Scoping review

“…Three promising salivary mRNA biomarker combinations have been prevalidated/validated using mock testing methods for the diagnosis of oral cavity and oropharyngeal carcinomas. 16,23,28 Mean sensitivity, specificity, and diagnostic accuracy for this marker group were 82%, 71%, and 72.5%, respectively. The combination of DUSP1, SAT, OAZ1 transcript deregulation yielded a high sensitivity, moderate specificity, and overall diagnostic accuracy of 63.7%.…”

“…Three promising salivary mRNA biomarker combinations have been prevalidated/validated using mock testing methods for the diagnosis of oral cavity and oropharyngeal carcinomas 16,23,28 . Mean sensitivity, specificity, and diagnostic accuracy for this marker group were 82%, 71%, and 72.5%, respectively.…”

“…Michailidou et al 23 included gene transcripts of proinflammatory cytokines— IL1B and IL8 to the aforementioned combination to obtain a higher diagnostic accuracy of 77.7%, albeit a lower sensitivity and negative predictive value was reported (Table 2). Recent verification endeavors by Oh and colleagues 28 using prospective saliva collection suggested the combination of CYP27A1 and SIAE from among six mRNA transcripts evaluated for the diagnosis of OSCC with good sensitivity, specificity, and accuracy reported.…”

Organoids and Liquid Biopsy in Oral Cancer Research

“…In this issue, three groups featured liquid biopsies to seek salivary, plasma, and urine biomarkers, including mRNA biomarkers, metabolites, and pro-inflammatory cytokines in OSCC. Oh et al reported salivary mRNA biomarkers for early detection of oral cancers [ 13 ]. They selected 30 candidate genes relevant to cancer from recent reports.…”