# An approach for developing a blood-based screening panel for lung cancer based on clonal hematopoietic mutations

## TL;DR

This study presents a new blood-based screening method for lung cancer using mutations in immune cells, which could improve early detection and reduce mortality.

## Contribution

The novel approach uses clonal hematopoietic mutations in blood to predict lung cancer with high accuracy using standard sequencing.

## Key findings

- A logistic regression model achieved 94.12% sensitivity and 85.96% specificity in predicting lung cancer from blood samples.
- The model used 98 pathogenic mutations identified from tumor-infiltrating immune cells in lung cancer samples.
- The approach relies on standard sequencing and a small set of mutations, distinguishing it from other liquid biopsy methods.

## Abstract

Early detection can significantly reduce mortality due to lung cancer. Presented here is an approach for developing a blood-based screening panel based on clonal hematopoietic mutations. Animal model studies suggest that clonal hematopoietic mutations in tumor infiltrating immune cells can modulate cancer progression, representing potential predictive biomarkers. The goal of this study was to determine if the clonal expansion of these mutations in blood samples could predict the occurrence of lung cancer. A set of 98 potentially pathogenic clonal hematopoietic mutations in tumor infiltrating immune cells were identified using sequencing data from lung cancer samples. These mutations were used as predictors to develop a logistic regression machine learning model. The model was tested on sequencing data from a separate set of 578 lung cancer and 545 non-cancer samples from 18 different cohorts. The logistic regression model correctly classified lung cancer and non-cancer blood samples with 94.12% sensitivity (95% Confidence Interval: 92.20–96.04%) and 85.96% specificity (95% Confidence Interval: 82.98–88.95%). Our results suggest that it may be possible to develop an accurate blood-based lung cancer screening panel using this approach. Unlike most other “liquid biopsies” currently under development, the approach presented here is based on standard sequencing protocols and uses a relatively small number of rationally selected mutations as predictors.