Abstract B061: Assessing saliva for cancer biomarker discovery: A liquid biopsy approach

Abstract Introduction: Liquid biopsy has been gaining traction as a replacement for invasive tumor biopsies in oncology. Several blood-based in vitro diagnostics have been approved by the FDA and other regulatory agencies, and efforts are being made to validate urine, saliva, and buccal swabs as alternative matrices. The primary aim of this study was to investigate the relative mRNA expression in paired blood and saliva samples from cancer patients and healthy individuals. Methods: We collected matched saliva and blood samples from 35 subjects, comprising 26 patients with prostate, breast, colon, lung, melanoma, and pancreatic cancers, and 9 healthy individuals. Samples were collected using Wren's proprietary stabilization buffer kit, and total RNA extracted by TRIzol-based Qiagen reagents. RNA sequencing (RNA-Seq) was performed on a Novaseq 6000 platform, and data was analyzed using high-performance computing (HPC) with PartekFlow software, employing the BWA aligner (hg38). We focused on comparing gene expression in cancers (as a group) compared to controls. Results: The total number of genes detected in saliva was 3,985, compared to 14,459 genes detected in blood samples. A substantial overlap was observed, with more than 92.8% of saliva-detected genes also found in blood. We also examined housekeeping gene detection in both matrices. In this set of 1,003 housekeeping genes, 30% (n=305) were expressed in both saliva and blood. When we narrowed the scope to only include the 1,154 cancer-related genes as listed by the OncoKB database, 88.3% were detected in saliva and/or blood, with 37.1% of these genes (n=429) were expressed in both saliva and blood. Lastly, we examined a set of 241 cancer-associated biomarkers utilized in RT-PCR-based diagnostic blood assays clinically validated by our laboratory. This subset analysis revealed that 23.2% of these biomarkers were expressed in both saliva and blood. Conclusion: Our data indicate that the majority of mRNA detected in saliva was also detected in blood, with differential expression observed in cancer patients compared to normal controls. Given the relatively high limit of detection (low sensitivity) using RNA-Seq technology compared to PCR and the relatively small number of subjects, the data may suggest that saliva could function as a surrogate biomarker matrix for blood. Citation Format: Srinivas V Koduru, Mark Kidd, Abdel B Halim. Assessing saliva for cancer biomarker discovery: A liquid biopsy approach [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B061.