Single-Cell Analysis in Lung Adenocarcinoma Implicates RNA Editing in Cancer Innate Immunity and Patient Prognosis

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• RNA editing, a process modifying RNA nucleotides, influences protein structure and abundance.
• Dysregulation of RNA editing is increasingly linked to cancer complexity and gene regulation.
• Previous studies observed RNA editing shifts in bulk tumors, but single-cell analysis remained unexplored.

Purpose of the Study:

• To investigate RNA editing patterns within individual cells of lung adenocarcinoma.
• To explore the relationship between RNA editing, drug resistance, immune response, and patient survival in lung cancer.

Main Methods:

• Profiling RNA editing in single cells from lung adenocarcinoma biopsies.
• Analyzing correlations between RNA editing levels, drug resistance markers, immune cell infiltration, and somatic mutation burden.
• Defining and evaluating a novel metric, RNA editing load, for prognostic prediction.

Main Results:

• Increased RNA editing trends in bulk tumors were found to be specific to cancer cells.
• Elevated RNA editing levels correlated with resistance to targeted therapy and were enriched at drug response-associated sites.
• Higher cancer cell RNA editing levels were associated with reduced antitumor innate immunity, including lower natural killer cell infiltration.
• RNA editing levels positively correlated with somatic point mutation burden, leading to the definition of RNA editing load.
• RNA editing load emerged as a stronger predictor of patient survival in lung cancer compared to DNA mutations.

Conclusions:

• This study offers the first single-cell analysis of RNA editing in cancer, revealing cell-type-specific patterns.
• RNA editing load is a significant prognostic biomarker in lung cancer, outperforming traditional DNA mutation metrics.
• Understanding RNA editing dynamics at the single-cell level provides new insights into cancer biology and therapeutic strategies.