Peripheral blood glycoproteomic biomarkers as a powerful new tool for the detection of nasopharyngeal carcinoma

Abstract Introduction: Nasopharyngeal carcinoma (NPC) is a malignancy characterized by distinct geographic, ethnic, and genetic differences. It presents a major threat to human health, particularly in East Asia and Southeast Asia. NPC commonly invades adjacent tissues and organs, resulting in complex and difficult to treat clinical presentations. NPC commonly remains largely asymptomatic during early disease stages due to its small primary foci. Hence, NPC patients are diagnosed mostly at advanced stage. Currently, no accurate and effective methods are available for the early diagnosis, evaluation, or prognosis for NPC. While Epstein-Barr virus (EBV) DNA and EBV serology tests have been advocated for early diagnosis and screening for NPC, the sensitivities of these two tests vary. due to the fact that only a small proportion of individuals infected with EBV ultimately develop NPC. The ability to detect neoplasms at early stages provides useful information for early intervention. We have recently demonstrated that interrogating the serum glycoproteome, using a proprietary platform that couples artificial intelligence (AI) to targeted liquid chromatography-massspectrometry (LC-MS) yields highly informative biomarkers in a range of neoplastic diseases. Experimental procedures in this proof-of-principle study, a total of 106 plasma samples (1:1 ratio of histologically confirmed cases of NPC and cancer-free controls), which were matched for age (average 49 years) were used. All subjects were male, from a multi-ethnic patient population in Malaysia, including three ethnic minority groups (Bidayuh, Iban and Kadaza). To identify diagnostic glycoprotein profiles for NPC we applied an in-house developed targeted glycoproteomics workflow, whereby plasma proteins were first digested with trypsin/LysC, followed by targeted analysis using LC-MS. The LC-MS generated chromatographic peaks were integrated using an in-house AI-based software for high throughput analysis and further subjected to multivariate statistical analysis. Summary of new data among the 579 glycopeptides interrogated in this study we found 62 glycopeptides statistically significantly abundant in NPC cases compared to healthy controls (at FDR <0.1). From these, we built a predictive algorithm that differentiates NPC cases from controls with high sensitivity and selectivity (AUC of 0.955). Six glycopeptide markers were found as associated with ethnicity. Conclusions: In summary, our results indicate that LC-MS-based glycopeptide profiling provides a highly accurate means of for differentiating NPC cases from healthy controls. Follow-up studies with larger sample size are currently in progress. Citation Format: Klaus Lindpaintner, Thi Thin Aye, Gege Xu, Rachel Rice, Alan Mtchell, Daniel Serie, A Malek, LH Low, Lp Tan, Ct Low, Cy Wong, H Sawali, Yy Yapp, As Khoo. Peripheral blood glycoproteomic biomarkers as a powerful new tool for the detection of nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2799.