Abstract 12P
Background
Although cancer is the second leading cause of death in the world, many cancer types including breast cancer, cervical cancer, lung cancer, and colorectal cancer can be efficiently treated if detected in their early stages, thus offering increased survival rates. Because of the ability of reflection from tumor tissue origin and systemic host response, plasma cell-free RNA (cfRNA) emerges as a highlight candidate. Previous studies have shown that plasma circulating tumor DNA (ctDNA) can serve as a potential biomarker for early detection of cancer. However, ctDNA-based assays demonstrated low sensitivity for the detection of breast cancer due to the low fraction and molecular heterogeneity of ctDNA. Unlike ctDNA, plasma cfRNA is released from the tumor microenvironment into circulation not only via cell death but also through cell-cell communication mechanisms. Cell-free mRNA (cfmRNA) is a subtype of cfRNA and its expression has been shown to reflect the transcriptomic alterations not only in tumor cells but also in other cell types in tumor microenvironments. Therefore, cfmRNAs have emerged as potential biomarkers for the early detection of breast cancer.
Methods
Here, we comprehensively profiled the cfmRNA transcriptome of breast cancer patients (n=24) and healthy individuals (n=33) by next-generation sequencing and identified differentially expressed cfmRNAs (DEM) by Deseq2. We further performed pathway enrichment analysis by the profiler, thus confirming their functional contribution to breast tumorigenesis.
Results
We found the set of 10955 DEMs, including breast-cancer markers like LAMP3, HSD11B1, PRTG, LPL, and identified 49 significantly enriched pathways. Interestingly, we discovered some DEMs (CD3D, CD8B, CD274, CTLA4, FOXP3, IL2RA) related to the distribution and function of tumor-infiltrating lymphocytes. Importantly, we demonstrated that the combination of tumor-specific and lymphocyte-related DEMs could differentiate blood samples of breast cancer patients and those of healthy individuals.
Conclusions
Our findings provide implications for the clinical utility of cfmRNAs for early detection of cancer types shedding low amounts of ctDNA such as breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Medical Genetics Institute, Ho Chi Minh, Vietnam.
Funding
Gene Solutions Joint Stock Company.
Disclosure
All authors have declared no conflicts of interest.
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