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

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.

Role of CD44 in Chemotherapy Treatment Outcome: A Scoping Review of Clinical Studies

“…The results were categorized according to the effect of CD44 expression on chemotherapy treatment outcome. In summary, three studies reported a positive effect of increased CD44 expression on chemotherapy treatment outcome [ 22 , 23 , 24 ], thirteen studies reported no significant effect between CD44 expression and chemotherapy treatment outcome [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], and twenty-four studies reported a significant negative effect of increased CD44 expression on chemotherapy treatment outcome [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. These studies are summarized in Table 1 , Table 2 and Table 3 , respectively.…”

Hyaluronic Acid Interacting Molecules Mediated Crosstalk between Cancer Cells and Microenvironment from Primary Tumour to Distant Metastasis

“…Poor differentiation, metastasis, and aggressive phenotype [27] Serum HA before chemotherapy Chemotherapy resistant; shortened OS and DFS [28,29] Endometrial cancer HA level Enhanced invasion, tumour grading and lymphatic involvement [30] Tumour stromal HA Tumour development [31] Peritumour stroma HA Tumour grade and invasion [32] Gastric cancer HA level Lymph node metastasis, cancer subtype specific, worse survival outcome. [33,34] Tumoral HA Cancer-subtype specific [35] Serum HA Elevated in gastric cancer [36] Lung cancer Baseline plasma HA Bone metastasis; chemotherapy efficacy [37] HA content Histological subtype specific, tumour differentiation, stage, recurrence and DFS [38] Tumour HA Level of malignancy, angiogenesis, patient survival, reflected in sputum [8] Mesothelioma HA level Increased in pleural fluid [39] High effusion HA level Better survival…”

The Hyaluronan/CD44 Axis: A Double-Edged Sword in Cancer

“…One of the key concerns is based on the observation that shorter bioactive HA fragments (e.g., LMW-HA) can interact with cancer cells and alter their activity in a different manner than that of HMA-HA [116]. Specifically, while HMW-HA maintains tissue homeostasis, HA breakdown products generated by hyaluronidases or ROS are often associated with enhanced invasion of cancer cells and tumor growth [117]. While current evidence does not suggest that this is the case for HA-conjugated drugs, ad hoc studies should be designed to rule out this possibility.…”