Splicing Factor Transcript Abundance in Saliva as a Diagnostic Tool for Breast Cancer

• Published in: Genes Vol. 11; no. 8; p. 880
• Main Authors: Bentata, Mercedes, Morgenstern, Guy, Nevo, Yuval, Kay, Gillian, Granit Mizrahi, Avital, Temper, Mark, Maimon, Ofra, Monas, Liza, Basheer, Reham, Ben-Hur, Asa, Peretz, Tamar, Salton, Maayan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.08.2020; MDPI
• Subjects: Adult; Age; Aged; Alternative splicing; Annotations; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; breast neoplasms; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Diagnosis; diagnostic techniques; Female; Gene expression; genes; Genetic aspects; Genetic transcription; Genomes; Health aspects; Humans; Isoforms; Mammography; messenger RNA; Metabolites; MicroRNAs; Middle Aged; neoplasm cells; patients; Proteins; Quality; RNA Splicing Factors - genetics; RNA Splicing Factors - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Saliva; Saliva - metabolism; screening; Splicing factors; Transcription; United States; women; Womens health; Israel; United States > US; Germany; United States; saliva; splicing factors; breast cancer; diagnosis
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes11080880

Breast cancer is the second leading cause of death in women above 60 years in the US. Screening mammography is recommended for women above 50 years; however, 22% of breast cancer cases are diagnosed in women below this age. We set out to develop a test based on the detection of cell-free RNA from saliva. To this end, we sequenced RNA from a pool of ten women. The 1254 transcripts identified were enriched for genes with an annotation of alternative pre-mRNA splicing. Pre-mRNA splicing is a tightly regulated process and its misregulation in cancer cells promotes the formation of cancer-driving isoforms. For these reasons, we chose to focus on splicing factors as biomarkers for the early detection of breast cancer. We found that the level of the splicing factors is unique to each woman and consistent in the same woman at different time points. Next, we extracted RNA from 36 healthy subjects and 31 breast cancer patients. Recording the mRNA level of seven splicing factors in these samples demonstrated that the combination of all these factors is different in the two groups (p value = 0.005). Our results demonstrate a differential abundance of splicing factor mRNA in the saliva of breast cancer patients.