Amino Acids

, Volume 51, Issue 5, pp 813–828 | Cite as

Clinical significance of LOXL4 expression and features of LOXL4-associated protein–protein interaction network in esophageal squamous cell carcinoma

  • Weijie Xie
  • Peiqi Huang
  • Bingli Wu
  • Sijie Chen
  • Zijian Huang
  • Junhao Wang
  • Hong Sun
  • Jianyi Wu
  • Lei Xie
  • Yinwei Cheng
  • Wenming Xie
  • Liyan Xu
  • Long-Qi Chen
  • Enmin LiEmail author
  • Haiying ZouEmail author
Original Article


Lysyl oxidase-like 4 (LOXL4), a member of the LOX family proteins, catalyzes oxidative deamination of lysine residues in collagen and elastin, which are responsible for maintaining extracellular matrix homeostasis. In this study, the mRNA expression of LOXL4 in seven esophageal squamous cell carcinoma (ESCC) cell lines and 15 ESCC pairs of clinical samples were examined. Furthermore, LOXL4 protein levels in the ESCC cell lines were determined using western blotting. With the use of immunofluorescence, LOXL4 was observed to be localized primarily in the cytoplasm, but was also present in the nucleus. In addition, the results indicated that the upregulated expression of LOXL4 was associated with poor survival in patients with ESCC even following curative resection (P = 0.010). Similar Kaplan–Meier estimator curves for proteins that interact with LOXL4, SUV39H1 (P = 0.014) and COL2A1 (P = 0.011), were plotted. The analyses based on the protein–protein interaction network depicted the expression of LOXL4 and its associated proteins as well as their functions, suggesting that LOXL4 and its associated proteins may serve a significant role in the development and progression of ESCC. In conclusion, the results of the present study suggest that LOXL4 is a potential biomarker for patients with ESCC, as well as SUV39H1 and COL2A1, and high expression levels of these genes are associated with poor prognosis in patients with ESCC.


Lysyl oxidase-like 4 Esophageal squamous cell carcinoma Protein–protein interaction network Expression pattern Clinical significance 



Lysyl oxidase


Lysyl oxidase-like 4


Suppressor of variegation 3–9 homolog 1


Collagen type II alpha 1 chain


Protein–protein interaction network


Esophageal squamous cell carcinoma


Hepatocellular carcinoma


Head and neck squamous cell carcinoma


Gastric cancer



This study was funded by grants from the National Natural Science Foundation of China (Nos. 81472613 and 81360331), the Natural Science Foundation of China-GuangDong Joint Fund (Nos. U1301227 and U1601229), the Science & Technology Planning Project of GuangDong Province (No. 2014A020212286), the Natural Science Foundation of Guangdong Province (No. 2018A030313664).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan AreaShantou University Medical CollegeShantouPeople’s Republic of China
  2. 2.Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouPeople’s Republic of China
  3. 3.Institute of Oncologic PathologyShantou University Medical CollegeShantouPeople’s Republic of China
  4. 4.Medical Bioinformatics CenterShantou University Medical CollegeShantouPeople’s Republic of China
  5. 5.Department of Thoracic Surgery, West China HospitalSichuan UniversityChengduPeople’s Republic of China

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