Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan

Abstract

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

Salivary proteome profiling of oral squamous cell carcinoma in a Hungarian population

“…More than 3700 salivary proteins have been identified by several research groups . Many proteins were declared potential salivary biomarkers of OSCC in different countries . In this study, we present a two‐stage approach for the discovery of candidate OSCC‐specific salivary biomarkers in the Hungarian population.…”

Association of overexpressed karyopherin alpha 2 with poor survival and its contribution to interleukin‐1β‐induced matrix metalloproteinase expression in oral cancer

“…Thus, the potential utility of salivary KPNA2 to serve as a prognostic or predictive biomarker needs to be further explored in large clinical cohorts with detection of its expression in the exosomes of oral cavity SCC cells. Recently, Yu et al used a quantitative proteomic approach to determine that the salivary concentrations of MMP‐1, MMP‐3, and MMP‐9 were significantly higher in patients with oral cavity SCC than those in healthy controls. In addition, the salivary levels of IL‐1β mRNA and protein were significantly higher in patients with oral cavity SCC than those in the matched healthy control subjects .…”

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

“…In OSCC, heterogeneous etiologic factors lead to gross changes in the genome and aberrations in key signaling pathways and this fact developed the idea of a combination of more than one salivary biomarker to serve as a reliable indicator . A panel consisting of MMP1, kininogen 1, annexin A2, and heat‐shock protein 5 (HSP5) was able to distinguish OSCC samples from non‐OSCC samples . In 2018, a study was conducted to evaluate the clinical value of two well‐known potential biomarkers, salivary N ‐α‐acetyltransferase 10 protein (Naa10p), and carcinoembryonic antigen (CEA), as well as their combined effect of diagnosing OSCC.…”