Hyaluronic Acid Correlates With Bone Metastasis and Predicts Poor Prognosis in Small-Cell Lung Cancer Patients.

Cong Zhao,Zhiyun Zhang,Yi Guo,Baolan Li,Lina Zhang,Ying Wang,Tongmei Zhang,Xingsheng Hu,Weiying Li,Yanxia Liu

doi:10.3389/fendo.2021.785192

Abstract

BackgroundHyaluronan (HA) is one of the essential elements of the extracellular matrix (ECM), involved in the onset of metastasis in various tumors. The interaction and binding of the ligand–receptor HA/cluster of differentiation-44 (CD44) regulate the physical and biochemical properties of the ECM, which correlates with an increased propensity toward metastasis and poor survival outcome. Our study aimed to explore HA for predicting metastasis and survival rate in patients with small-cell lung cancer (SCLC).Materials and MethodsThis prospective cohort study recruited 72 patients with SCLC. Plasma HA and CD44 levels were assayed by enzyme-linked immunosorbent assay (ELISA) for 72 cases before initial systematic treatment (baseline samples), and plasma HA was detected via after-2-cycle-chemotherapy (A-2-C-CT) in 48 samples. Logistic regression analysis and the Cox proportional risk model were used to determine the independent predictors of distant metastasis and survival rate of patients.ResultsBaseline plasma HA was notably associated with bone metastasis (BM) [OR (95% CI = 1.015 (1.006–1.024), p = 0.001]. Multivariate logistic regression analysis showed that baseline plasma HA was chosen as an independent predictor of BM. Either baseline HA or CD44 or both were associated with BM. Dynamic alteration of HA was notably associated with A-2-C-CT clinical efficacy. Multivariate Cox regression analysis in forward likelihood ratio showed that A-2-C-CT HA was an independent predictor of progression-free survival (PFS) and overall survival (OS).ConclusionsHA appears to be used as an independent predictive factor for BM, and the dynamic detection of HA can predict prognosis in SCLC patients. The mechanism of the HA/CD44 axis in BM of SCLC deserves further exploration.

Highlights

Lung cancer is the second most newly diagnosed cancer and the chief cause of cancer death
We assessed demographic and pretreatment clinical features, including the sex, age, and smoking history of the patients; ECOG-performance status (PS); tumor staging according to the eighth edition of the American Cancer TNM Commission System [28]; distant metastasis; and the evaluation of clinical efficacy according to RECIST version 1.1 [27]
In the univariate logistic regression analysis, HA was notably associated with bone [OR (95% CI = 1.015 (1.006–1.024), p = 0.001], and the other parameters in Table S2 did not correlate to HA (p > 0.05)

Summary

Introduction

Lung cancer is the second most newly diagnosed cancer and the chief cause of cancer death. Small-cell lung cancer (SCLC), characterized by rapid relapse and poor survival, accounts for approximately 10%–15% of lung cancer [1,2,3]. Despite the high response rate to frontline platinum-containing regimens, resistance and relapse after chemotherapy are inevitable for the majority of patients. The prognosis of SCLC patients with the same limited stage is very different: some immortality, some quickly progress in concurrent radiochemotherapy, and a few extensive-stage patients live long. There is a lack of effective prognosis markers in SCLC. The interaction and binding of the ligand–receptor HA/cluster of differentiation-44 (CD44) regulate the physical and biochemical properties of the ECM, which correlates with an increased propensity toward metastasis and poor survival outcome. Our study aimed to explore HA for predicting metastasis and survival rate in patients with small-cell lung cancer (SCLC)

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