Cancer type classification using plasma cell-free RNAs derived from human and microbes

Area of Science:

• Oncology
• Microbiology
• Genomics

Background:

• Cell-free nucleic acids (cfNAs) in plasma are increasingly recognized for cancer monitoring.
• A portion of plasma cfNAs originates from microbes and is relevant to cancer.
• Understanding plasma cell-free RNAs (cfRNAs) in cancer is crucial for diagnostic advancements.

Purpose of the Study:

• To profile plasma cfRNAs in five cancer types and healthy donors using RNA-sequencing.
• To investigate the diagnostic and tumor-site determination potential of human and microbe-derived cfRNAs.

Main Methods:

• RNA-sequencing of approximately 300 plasma samples from cancer patients and healthy donors.
• Computational analysis to detect and filter human and microbe-derived cfRNAs.
• Receiver Operating Characteristic (ROC) curve analysis for diagnostic accuracy and recall analysis for tumor site determination.

Main Results:

• Microbe-derived cfRNAs were consistently detected after careful contamination filtering.
• Combined human and microbial cfRNAs achieved an area under the ROC curve of approximately 0.9 for cancer detection.
• Incorporating microbial features improved tumor site determination recall by approximately 8% compared to human features alone.
• Enriched pathways and microbial signatures suggest immunosuppression in a fraction of cancer patients.

Conclusions:

• Plasma cfRNAs, both human and microbe-derived, possess significant diagnostic value for cancer detection.
• The combination of human and microbial cfRNAs enhances cancer type specificity and aids in primary tumor site determination.
• These findings support the clinical utility of cfRNAs as non-invasive biomarkers in oncology.