Low‑density lipoprotein promotes lymphatic metastasis of esophageal squamous cell carcinoma and is an adverse prognostic factor

Deng,Hongbin; Zhou,Tao; Mo,Xinkai; Liu,Chengxin; Yin,Yong

doi:10.3892/ol.2018.9683

Low‑density lipoprotein promotes lymphatic metastasis of esophageal squamous cell carcinoma and is an adverse prognostic factor

Authors:
- Hongbin Deng
- Tao Zhou
- Xinkai Mo
- Chengxin Liu
- Yong Yin
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Affiliations: Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China, Department of Laboratory, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
Published online on: November 9, 2018 https://doi.org/10.3892/ol.2018.9683
Pages: 1053-1061
Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The purpose of the current study was to investigate the prognostic role of preoperative serum lipid levels in patients with esophageal squamous cell carcinoma (ESCC) and to preliminarily explore the mechanism of serum lipids in this disease. Preoperative lipids, including total cholesterol, low‑density lipoprotein (LDL) cholesterol, high‑density lipoprotein (HDL) cholesterol and triglyceride levels, were assessed in 242 patients with ESCC. To eliminate the influence of nutritional status, all patients had previously undergone esophagectomy. Univariate and multivariate Cox regression analyses were performed to identify predictors of overall survival (OS). Associations between significant lipid targets and clinical features were then analyzed and the results were validated using TE‑1 and ECa109 esophageal cancer cell lines. The cell proliferation was evaluated with a Cell Counting Kit‑8 (CCK8) assay and the cell cycle was assessed with propidium iodide staining and ﬂow cytometry. Univariate analysis revealed that HDL (P=0.048), LDL (P=0.020), Pathological T‑staging status (pT status) (P=0.001), Pathological N‑staging status (pN status) (P=0.001) and histological differentiation (P=0.002) were significantly associated with OS. Based on multivariate analysis, LDL [hazard ratio (HR)=2.164, P=0.005], pT status (HR=1.714, P=0.001), pN status (HR=1.966, P=0.001) and histological differentiation (HR=4.083, P=0.002) were risk factors in patients with ESCC. A high LDL level (>3.12 mmol/l) was associated with sex (P=0.001), tumor location (P=0.004) and a higher susceptibility to lymphatic metastasis (P=0.007). A CCK8 assay demonstrated that LDL promoted TE‑1 and ECa109 cell proliferation, and ﬂow cytometry analysis revealed that treatment with LDL at an appropriate concentration resulted in an accumulation of cells in G2 phase and decreased the number of cells in G1 phase. In summary, the current study identified that preoperative LDL serum level serves an important role in predicting ESCC outcome as LDL promotes lymphatic metastasis. Furthermore, a preliminary mechanism for this association has been validated in vitro.

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