Research Papers:

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

Jun Gong, Michelle Guan, Haesoo Kim, Natalie Moshayedi, Sejal Mehta, Galen Cook-Wiens, Brent K. Larson, Jenny Zhou, Rishi Patel, Isaac Lapite, Veronica R. Placencio-Hickok, Richard Tuli, Ronald B. Natale and Andrew E. Hendifar _

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Oncotarget. 2022; 13:1202-1214. https://doi.org/10.18632/oncotarget.28304

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Jun Gong1, Michelle Guan1, Haesoo Kim1, Natalie Moshayedi1, Sejal Mehta1, Galen Cook-Wiens2, Brent K. Larson3, Jenny Zhou1, Rishi Patel1, Isaac Lapite1, Veronica R. Placencio-Hickok1, Richard Tuli4,5, Ronald B. Natale6 and Andrew E. Hendifar1

1 Gastrointestinal and Neuroendocrine Malignancies, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA

2 Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA

3 Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA

4 Department of Radiation Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA

5 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

6 Lung Cancer Research Program, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA

Correspondence to:

Andrew E. Hendifar, email: [email protected]

Keywords: hyaluronan; hyaluronic acid; biomarker; prognostic; predictive

Received: August 04, 2022     Accepted: October 12, 2022     Published: November 02, 2022

Copyright: © 2022 Gong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.

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