Abstract
We evaluated whether hyaluronan (HA) levels in the sputum could be used as a noninvasive tool to predict progressive disease and treatment response, as detected in a computed tomography scan in non-small cell lung cancer (NSCLC) patients. Sputum samples were collected from 84 patients with histological confirmation of NSCLC, 33 of which were in early-stage and 51 in advanced-stage disease. Patients received systemic chemotherapy (CT) after surgery (n=36), combined CT and immunotherapy (IO) (n=15), or targeted therapy for driver mutation and disease relapse (N=4). The primary end-point was to compare sputum HA levels in two different concentrations of hypertonic saline solution with overall survival (OS) and the secondary and exploratory end-points were radiologic responses to treatment and patient outcome. Higher concentrations of HA in the sputum were significantly associated to factors related to tumor stage, phenotype, response to treatment, and outcome. In the early stage, patients with lower sputum HA levels before treatment achieved a complete tumor response after systemic CT with better progression-free survival (PFS) than those with high HA levels. We also examined the importance of the sputum HA concentration and tumor response in the 51 patients who developed metastatic disease and received CT+IO. Patients with low levels of sputum HA showed a complete tumor response in the computed tomography scan and stable disease after CT+IO treatment, as well as a better PFS than those receiving CT alone. HA levels in sputum of NSCLC patients may serve as a candidate biomarker to detect progressive disease and monitor treatment response in computed tomography scans.
Highlights
In recent years, innovative-targeted drug therapies have emerged as a result of our deeper understanding of the molecular biology of malignant tumors
This increased mortality in lung cancer patients is often associated with three main causes: the absence of an established screening protocol to detect early-stage disease, the fact that the first symptoms usually arise in advanced stages, and the lack of biomarkers to monitor therapeutic response and to detect disease progression and poor prognosis (3)
Male patients older than 58 years had a significantly higher HA concentration in sputum samples collected with 7% saline (P=0.01), as did smokers (P=0.002) and patients with squamous cell carcinoma (P=0.03)
Summary
Innovative-targeted drug therapies have emerged as a result of our deeper understanding of the molecular biology of malignant tumors These therapies have improved the outcome of non-small cell lung cancer (NSCLC) patients (1), lung cancer remains the world’s deadliest type of cancer to this day (2). The genomic, proteomic, and transcriptomic profiling of lung cancers is being complemented by the study of the biochemical properties of endogenous metabolites produced by malignant cells (4) In this regard, a major polysaccharide component of the extracellular matrix, hyaluronan (HA), has attracted the attention of researchers because of its biochemical properties and its ability to control cell proliferation and migration through interactions with cell-surface receptors and binding molecules (5). HA is primarily considered an extracellular molecule, but it can
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