Tumor hyaluronan as a novel biomarker in non-small cell lung cancer: A retrospective study

Introduction: Hyaluronan (HA) accumulation is associated with tumorigenesis and aggressive tumor behavior. Aims: We investigated the biomarker potential of HA in non-small cell lung cancer (NSCLC). Methods: HA levels were scored using affinity histochemistry in 137 NSCLC samples stratified by HA score ≤10, 11–20, 21–30, and >30 with HA-high defined as ≥25% expression in the extracellular matrix (ECM) of the tumor surface area. Overall survival (OS) and time to progression from initiation of taxane therapy (TTP) were compared using log-rank tests based on HA score. Results: Of 122 patients with recurrent/metastatic NSCLC, 93 had mean HA scores that were not significantly different across clinicopathologic variables. Frequency of HA-high tumors did not differ by histology (34/68 adenocarcinomas vs. 12/25 squamous tumors, Fisher’s p = 1.0000). Median OS for recurrent/metastatic adenocarcinoma was 35.5 months (95%, 23.6–50.3) vs. 17.9 months for squamous (95%, 12.7–37.0, log-rank test, p = 0.0165). OS was not significantly different by HA quartiles, high or low (<25) HA score and tumor histology, and HA biopsy site (all p > 0.05). Median TTP (n = 98) significantly differed by HA quartile (2.8 months for HA score ≤10; 5.0 months for 11–20; 7.9 months for 21–30; 3.9 months for >30, p = 0.0265). Improved TTP trended in HA-high over HA-low tumors (n = 98, p = 0.0911). Conclusion: In this NSCLC cohort, tumor HA level represents a potential biomarker for TTP, which remains a cornerstone of NSCLC therapy. Further validation is warranted to identify the HA accumulation threshold associated with clinical benefit.