# Comprehensive circRNA profiling of platelets and exosomes identifies hsa_circ_0061274 as a novel biomarker for lung adenocarcinoma

## TL;DR

This study identifies a specific circular RNA in platelets that could help detect lung cancer early using a simple blood test.

## Contribution

Platelet-derived hsa_circ_0061274 is a novel, minimally invasive biomarker for early detection of lung adenocarcinoma.

## Key findings

- Platelets contain 15–20 times more distinct circRNAs than plasma exosomes.
- hsa_circ_0061274 is significantly down-regulated in lung adenocarcinoma platelets.
- hsa_circ_0061274 achieves an AUC of 0.85 in distinguishing LUAD from healthy controls.

## Abstract

Lung adenocarcinoma (LUAD) is usually detected late; sensitive, minimally invasive early-detection tools are urgently needed. Circular RNAs (circRNAs) in liquid biopsies are promising cancer biomarkers, yet it remains unclear which blood component—platelets or plasma exosomes—offers the richest and most informative circRNA source.

High-throughput RNA sequencing was performed on platelets and plasma exosomes collected from LUAD patients and age-matched healthy donors. Differential circRNAs expression was analyzed after stringent quality filtering and normalization. A candidate reference gene was selected by stability testing (geNorm, NormFinder); diagnostic performance of the top LUAD-associated circRNA was validated in independent cohorts encompassing healthy controls and patients with benign pulmonary nodules; ROC curves were generated and AUCs calculated.

Platelets contained 15–20-fold more distinct circRNAs than plasma exosomes. hsa_circ_0001380 was identified as a stably expressed reference suitable for platelet circRNA quantification. hsa_circ_0061274 was significantly down-regulated in LUAD platelets (log2FC ≈ −1.8, FDR < 0.01). In validation cohorts, hsa_circ_0061274 discriminated LUAD from healthy controls with an AUC of 0.85 (95% CI 0.79–0.91), from benign pulmonary nodules with an AUC of 0.75 (95% CI 0.68–0.82), and stage I LUAD with an Area Under the Curve (AUC) of 0.68 (95% CI 0.60–0.76). Platelet-derived circRNAs thus provide robust, minimally invasive biomarkers for early LUAD detection and pulmonary nodule characterization.