Non-invasive detection of hTERT mRNA in deep-cough swabs for early diagnosis of lung cancer

TL;DR

This study introduces a non-invasive method using deep-cough swabs to detect lung cancer early by measuring hTERT mRNA levels in airway secretions.

Contribution

The novel contribution is a non-invasive diagnostic protocol using hTERT mRNA detection in deep-cough swabs for early-stage lung cancer.

Findings

The assay achieved 90.6% sensitivity for stage IA lung cancer detection.

It showed 95.9% specificity in distinguishing cancer from non-cancer cases.

The method was effective across different histological subtypes and smoking statuses.

Abstract

Lung cancer remains the leading cause of cancer-related mortality globally, with current screening methods like low-dose computed tomography (LDCT) limited by radiation risks and false negatives. Non-invasive diagnostic tools are urgently needed.

We developed a deep-cough swab protocol coupled with rapid RNA extraction and direct RT-qPCR to detect human telomerase reverse transcriptase (hTERT) mRNA in airway secretions. The assay was validated using exosomes from lung cancer cell lines and applied to 300 participants (106 early-stage lung cancer patients, 142 benign pulmonary nodule cases, and 52 healthy controls).

The assay achieved 90.6% sensitivity (95% CI: 85.1%–96.2%) for stage IA lung cancer and 95.9% specificity (95% CI: 93.1%–98.7%) in non-cancer controls. ROC analysis demonstrated excellent discrimination (AUC = 0.97, p < 0.0001). Sensitivity was consistent across histological subtypes and unaffected by smoking status (p > 0.05).

Deep-cough swab detection of hTERT mRNA provides a clinically viable, non-invasive method for auxiliary diagnosis of early-stage lung cancer, potentially complementing CT screening for pulmonary nodule management.

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