The Airway Transcriptome as a Biomarker for Early Lung Cancer Detection

Abstract

Lung cancer remains the leading cause of cancer-related death due to its advanced stage at diagnosis. Early detection of lung cancer can be improved by better defining who should be screened radiographically and determining which imaging-detected pulmonary nodules are malignant. Gene expression biomarkers measured in normal-appearing airway epithelium provide an opportunity to use lung cancer-associated molecular changes in this tissue for early detection of lung cancer. Molecular changes in the airway may result from an etiologic field of injury and/or field cancerization. The etiologic field of injury reflects the aberrant physiologic response to carcinogen exposure that creates a susceptible microenvironment for cancer initiation. In contrast, field cancerization reflects effects of "first-hit" mutations in a clone of cells from which the tumor ultimately arises or the effects of the tumor on the surrounding tissue. These fields might have value both for assessing lung cancer risk and diagnosis. Cancer-associated gene expression changes in the bronchial airway have recently been used to develop and validate a 23-gene classifier that improves the diagnostic yield of bronchoscopy for lung cancer among intermediate-risk patients. Recent studies have demonstrated that these lung cancer-related gene expression changes extend to nasal epithelial cells that can be sampled noninvasively. While the bronchial gene expression biomarker is being adopted clinically, further work is necessary to explore the potential clinical utility of gene expression profiling in the nasal epithelium for lung cancer diagnosis, lung cancer risk assessment, and precision medicine for lung cancer treatment and chemoprevention. .

scPred: accurate supervised method for cell-type classification from single-cell RNA-seq data

“…However, importantly, tumor cells originate from the same cell subtypes of one or more of the original healthy cells in a tissue. Numerous methods exist for classifying (or diagnosing) a whole tissue biopsy as either cancerous or non-cancerous based on DNA genotyping [42], transcriptome profiling [43, 44], or histochemistry [45, 46]. Most of these methods work well, but are unable to accurately classify heterogeneity at a cellular level, and do not work if the percentage of tumor cells in a biopsy is small.…”

Biomarkers in Lung Cancer Screening: Achievements, Promises, and Challenges

“…59 RNA Airway and Nasal Signature. On the basis of the "field of injury" paradigm, 60 airway epithelial gene expression has been developed as a diagnostic biomarker for lung cancer. The initial studies focused on bronchial airway epithelial cells obtained by endobronchial brushings of the mainstem bronchus.…”

Lung Cancer Screening, towards a Multidimensional Approach: Why and How?

“…Indeed, there is some evidence that nontumor adjacent cells share some molecular characteristics with tumor cells. In this context, it has been recently demonstrated that most genetic alterations expressed in smoker patients are not only found in bronchial but also in the nasal epithelium [31]. Thus, LC-associated gene expression assessment in nontumor respiratory epithelium may represent a promising field of development to optimize LC risk evaluation and, thus, to better understand its pathogenesis [31].…”